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Zakariah M, Agishi G, Musa EZ, Dasa JJ, Majama YB, Gazali YA, Mahdy MAA. Rate of spermatogenic cell apoptosis in the testis of domestic chicken (Gallus gallus domesticus) at different age groups. Poult Sci 2025; 104:104953. [PMID: 40031382 PMCID: PMC11919428 DOI: 10.1016/j.psj.2025.104953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 02/25/2025] [Indexed: 03/05/2025] Open
Abstract
In both normal and pathological conditions, excess spermatogenic cells in the testicular tissue are known to be removed by the mechanism of apoptosis. There are a few studies on spermatogenic cell apoptosis in avian species. Therefore, the purpose of this study was to evaluate the rate of spermatogenic cell apoptosis in three different age groups of the local domestic chicken (Gallus gallus domesticus). Samples were collected from the testes of domestic chicken at three different reproductive stages; pre-pubertal, pubertal, and adult. The samples were subjected to transmission electron microscopy (TEM) and flow cytometry evaluations. TEM results revealed the morphological characteristics of apoptotic cells which included irregular nuclear and plasma membranes in the early stages of apoptosis, nuclear membrane rupture, nuclear material condensation, and fragments of apoptotic bodies in the later stages of apoptosis. The flow cytometry results revealed a significant difference between the mean percentage of apoptotic spermatogenic cells for the three age groups (P < 0.05). Post hoc analysis revealed a significant difference in the adult age group relative to the pre-pubertal age group. However, there was no significant difference between apoptotic spermatogenic cells of the pre-pubertal and the pubertal, and between the pubertal and the adult age groups. In conclusion, the present study revealed a gradual increase in the rate of apoptotic spermatogenic cells in the testes of domestic chicken during the pre-pubertal, pubertal, and adult age groups.
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Affiliation(s)
- Musa Zakariah
- Department of Veterinary Anatomy, College of Veterinary Medicine, Federal University of Agriculture, P. M. B. 28, Zuru, Kebbi, Nigeria; Department of Veterinary Anatomy, Faculty of Veterinary Medicine, P. M. B. 1069 University of Maiduguri, Maiduguri, Nigeria.
| | - Geado Agishi
- Department of Veterinary Pathology, College of Veterinary Medicine, Federal University of Agriculture, P. M. B. 28, Zuru, Kebbi, Nigeria
| | - Esther Z Musa
- Department of Biological Science, College of Science, Federal University of Agriculture, P.M. B. 28, Zuru, Kebbi, Nigeria
| | - Josephine J Dasa
- Department of Biological Science, College of Science, Federal University of Agriculture, P.M. B. 28, Zuru, Kebbi, Nigeria
| | - Yagana B Majama
- Department of Veterinary Anatomy, Faculty of Veterinary Medicine, P. M. B. 1069 University of Maiduguri, Maiduguri, Nigeria
| | - Yagana A Gazali
- Department of Veterinary Anatomy, Faculty of Veterinary Medicine, P. M. B. 1069 University of Maiduguri, Maiduguri, Nigeria
| | - Mohammed A A Mahdy
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt; Department of Anatomy and Histology, Faculty of Veterinary Medicine, King Salman International University, Ras Sudr, Egypt
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Tekin V, Altintas F, Oymak B, Unal EB, Tunc-Ata M, Elmas L, Kucukatay V. S-Sulfocysteine's toxic effects on HT-22 cells are not triggered by glutamate receptors, nor do they involve apoptotic or genotoxicity mechanisms. Cytotechnology 2025; 77:32. [PMID: 39749013 PMCID: PMC11688261 DOI: 10.1007/s10616-024-00697-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 12/24/2024] [Indexed: 01/04/2025] Open
Abstract
S-Sulfocysteine (SSC) is a metabolite derived from the metabolism of sulfur-containing amino acids. It has been implicated in neurotoxicity observed in children with sulfite oxidase deficiency. The aim of our study was to confirm the neurotoxic effects of SSC using a mouse hippocampal cell line (HT-22) and to investigate the role of apoptosis in these effects, especially in terms of caspase-3 activation and genotoxicity. Based on the viability graph obtained following increasing concentrations of SSC, we determined the LC50 dose of SSC to be 125 µM by probit analysis. The cytotoxic effects of SSC were not reversed by glutamate receptor blocker administration. However, SSC treatment did not induce caspase-3 activation or induce DNA damage. Our results showed that SSC has a cytotoxic effect on neurons like glutamate, but glutamate receptor blockers reversed glutamate-induced toxicity, while these blockers did not protect neurons from SSC toxicity. The absence of caspase-3 activation and DNA fragmentation, which are indicative of apoptosis, in SSC-induced cell death suggests that alternative cell death pathways, such as necrosis and oxytosis may be implicated. Further research is necessary to fully elucidate SSC-induced cell death. The aim of our study was to confirm the neurotoxic effects of SSC using a mouse hippocampal cell line (HT-22) and to investigate the role of apoptosis in these effects, especially in terms of caspase-3 activation and genotoxicity.
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Affiliation(s)
- Volkan Tekin
- Department of Physiology, Gülhane Faculty of Medicine, University of Health Sciences, Ankara, Türkiye
| | - Fatih Altintas
- Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye
| | - Burak Oymak
- Department of Physiology, Prof. Dr. Cemil Taşcıoğlu City Hospital, Istanbul, Türkiye
| | - Egem Burcu Unal
- Department of Physiology, Adana City Education and Research Hospital, Adana, Türkiye
| | - Melek Tunc-Ata
- Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye
| | - Levent Elmas
- Department of Medical Biology, Faculty of Medicine, Bakırçay University, İzmir, Türkiye
| | - Vural Kucukatay
- Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye
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Caliskan M, Ilikci‐Sagkan R, Bayrak G, Ozlem‐Caliskan S. Monitoring Apoptosis and Myeloid Differentiation of Acridine Orange-Mediated Sonodynamic Therapy-Induced Human Promyelocytic Leukemia HL60 Cells. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2025; 44:15-34. [PMID: 39257135 PMCID: PMC11632649 DOI: 10.1002/jum.16575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 09/12/2024]
Abstract
OBJECTIVES In the treatment of acute myeloid leukemia (AML), conventional therapies can lead to severe side effects and drug resistance. There is a need for alternative treatments that do not cause treatment resistance and have minimal or no side effects. Sonodynamic therapy (SDT), due to its noninvasive, multiple repeatability, localized treatment feature and do not cause treatment resistance, emerges as an alternative treatment option. However, it has not received sufficient attention in the treatment of AML especially acute promyelocytic leukemia (APL). The aim of the study was to investigate the potential differentiation and antileukemic effects of acridine orange (AO)-mediated SDT on HL60 cells. METHODS Cell viability was determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) method in the control, ultrasound, AO concentrations, and ultrasound-exposed AO concentrations groups. Transmission electron microscopy (TEM) was used to determine morphology, and flow cytometry was used to determine apoptosis, DNA cycle, cell volume, mitochondria membrane potential (Δψm), reactive oxygen species (ROS) production, and differentiation markers (CD11b and CD15) expressions. Additionally, toluidine blue staining for semithin sections was used to determine differentiation. RESULTS The cytotoxicity of AO-mediated SDT on HL60 cells was significantly higher than other groups, and TEM images showed that it caused various morphological changes typical for apoptosis. Flow cytometry results showed the presence of early apoptosis, subG1 arrest, loss of Δψm, increase of intracellular ROS production, decreased cell volume, and increased expression of CD11b (1.3-fold) antigen and CD15 (1.2-fold) antigen. CONCLUSION Data showed that AO-mediated SDT significantly induced apoptosis in HL60 cells. Increased expression of CD11b and CD15 antigens and morphological findings demonstrated that AO-mediated SDT contributes to granulocytic differentiation in HL60 cells. AO-mediated SDT has potential as an alternative treatment of APL.
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Affiliation(s)
- Metin Caliskan
- Department of Medical Biology, Faculty of MedicineUsak UniversityUsakTurkey
| | | | - Gulsen Bayrak
- Department of Histology and Embryology, Faculty of MedicineUsak UniversityUsakTurkey
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Singh H, Singh T, Singh V, Singh B, Kaur S, Ahmad SF, Al-Mazroua HA, Singh B. Ehretia laevis mitigates paracetamol- induced hepatotoxicity by attenuating oxidative stress and inflammation in rats. Int Immunopharmacol 2024; 143:113565. [PMID: 39504859 DOI: 10.1016/j.intimp.2024.113565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/20/2024] [Accepted: 10/31/2024] [Indexed: 11/08/2024]
Abstract
Hepatotoxicity is caused due to intake of drug or any chemical above the therapeutic range or as overdose. Current therapies for the management of hepatotoxicity are associated with several side effects. The present study was envisaged to explore the hepatoprotective potential of Ehretia laevis (E. laevis) in paracetamol (PCM) induced hepatotoxicity. All the plant extracts and fractions were evaluated for antioxidant and antiproliferative potential using various in vitro assays. Hepatotoxicity was induced in rats using a standardized single oral dose of PCM (3 g/kg). The aqueous fraction of E. laevis (AFEL) exhibited significant antioxidant and antiproliferative activity as compared to methanol extract of E. laevis (MEEL) in vitro. Moreover, treatment with AFEL (25, 50 and 100 mg/kg) decreased serum hepatic markers, attenuate the oxidative stress, inflammation and histopathological changes. LC-MS analysis of AFEL showed the presence of rutin, quercetin and kaempferol. Rutin was found to be in higher concentration, therefore it was docked on TNF-α. Its overall binding mode supports its capability to make complex with TNF-α. The finding of the study suggested significant antioxidant, antiproliferative, and hepatoprotective potential of E. laevis in paracetamol induced hepatotoxicity which could be attributed to the presence of various polyphenols.
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Affiliation(s)
- Hasandeep Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India; Khalsa College of Pharmacy, Amritsar 143005, India.
| | - Tanveer Singh
- Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
| | - Varinder Singh
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India.
| | - Brahmjot Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
| | - Sarabjit Kaur
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
| | - Sheikh F Ahmad
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Haneen A Al-Mazroua
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Balbir Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
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Motta JVDO, Gomes DS, Silva LLD, Oliveira MSD, Bastos DSS, Resende MTCS, Alvim JRL, Reis AB, Oliveira LLD, Afzal MBS, Serrão JE. Effects of sublethal concentration of thiamethoxam formulation on the wild stingless bee, Partamona helleri Friese (Hymenoptera: Apidae): Histopathology, oxidative stress and behavioral changes. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 957:177626. [PMID: 39566631 DOI: 10.1016/j.scitotenv.2024.177626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 11/13/2024] [Accepted: 11/16/2024] [Indexed: 11/22/2024]
Abstract
Bees are pollinators of native and cultivated plants around the world. However, several factors are contributing to the decrease in their populations in recent years, with emphasis on the increasing use of insecticides in agriculture. Thiamethoxam is a neonicotinoid neurotoxicant, which binds to nicotinic acetylcholine receptors, causing hyperexcitation, paralysis and death of insects. Although thiamethoxam's target is the nervous system, it can affect other organs through ingestion, such as the midgut, affecting non-target insects such as bees. Partamona helleri Friese (Hymenoptera: Apidae) is a stingless bee, pollinator of several native and cultivated botanical families, and can be exposed to sublethal concentrations of thiamethoxam. This study evaluated the side effects of chronic oral exposure to thiamethoxam on the midgut, oxidative stress and behavior of P. helleri workers. The bees were exposed orally, for 7 days, to the approximate sublethal concentration of thiamethoxam found in pollen grains (0.09 ng/g). The results demonstrated changes in the midgut epithelium of workers treated with thiamethoxam, such as cytoplasmic vacuolization, cellular protrusions, increased apocrine transfer, mitochondrial damage, decreased proteins and neutral polysaccharides and the presence of cells undergoing autophagy and apoptosis. Sublethal concentration of thiamethoxam also induced oxidative stress, evidenced by changes in the activities of detoxification enzymes and antioxidant markers. Finally, thiamethoxam affects the bee's behavior, driving the distance covered and walking speed of this insect. The results indicate that the exposure of P. helleri workers to sublethal concentration of thiamethoxam have negative impacts upon midgut morphology and physiology and behavioral traits.
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Affiliation(s)
| | - Davy Soares Gomes
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
| | - Laryssa Lemos da Silva
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
| | - Mateus Soares de Oliveira
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
| | - Daniel Silva Sena Bastos
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil
| | | | | | - Aline Beatriz Reis
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
| | | | | | - José Eduardo Serrão
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
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Jagaran K, Habib S, Singh M. Bio-Inspired Polymeric Solid Lipid Nanoparticles for siRNA Delivery: Cytotoxicity and Cellular Uptake In Vitro. Polymers (Basel) 2024; 16:3265. [PMID: 39684010 DOI: 10.3390/polym16233265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Nanomedicine has introduced strategies that provide precise diagnosis and treatment with fewer side effects than traditional therapies. Treatments for neurodegenerative disorders, including Parkinson's disease, are palliative, necessitating an innovative delivery system with a curative function. This study investigated a solid lipid nanoparticle (SLNP) system's ability to bind and safely deliver siRNA in vitro. SLNPS were formulated using sphingomyelin and cholesterol, with Ginkgo biloba leaf extract (GBE) incorporated to enhance biocompatibility and neuroprotection. Poly-L-lysine (PLL) functionalization ensured successful siRNA binding, safe transport, and protection from nuclease degradation. SLNPs were physicochemically characterized, with binding and protection of siRNA assessed using agarose gels. Cytotoxicity, apoptotic induction, and cellular uptake studies were undertaken in the human neuroblastoma (SH-SY5Y) and embryonic kidney (HEK293) cells. The GBE-PLL-SLNPs had an average size of 93.2 nm and demonstrated enhanced binding and protection of the siRNA from enzyme digestion, with minimal cytotoxicity in HEK293 (<10%) and SH-SY5Y cells (<15%). Caspase 3/7 activity was significantly reduced in both cells, while efficient cellular uptake was noted. The present study provided a solid basis as a proof of principle study for future applications of the potential therapeutic in vitro, promising to address the unmet medical needs of patients with neurological disorders.
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Affiliation(s)
- Keelan Jagaran
- Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
| | - Saffiya Habib
- Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
| | - Moganavelli Singh
- Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
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Kunjiappan S, Panneerselvam T, Pavadai P, Balakrishnan V, Pandian SRK, Palanisamy P, Sankaranarayanan M, Kabilan SJ, Sundaram GA, Tseng WL, Kumar ASK. Fabrication of folic acid-conjugated pyrimidine-2(5H)-thione-encapsulated curdlan gum-PEGamine nanoparticles for folate receptor targeting breast cancer cells. Int J Biol Macromol 2024; 277:134406. [PMID: 39097067 DOI: 10.1016/j.ijbiomac.2024.134406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/05/2024]
Abstract
In this study 5-((2-((3-methoxy benzylidene)-amino)-phenyl)-diazenyl)-4,6-diphenyl pyrimidine-2(5H)-thione was synthesized. The pharmacological applications of pyrimidine analogs are restricted due to their poor pharmacokinetic properties. As a solution, a microbial exopolysaccharide (curdlan gum) was used to synthesize folic acid-conjugated pyrimidine-2(5H)-thione-encapsulated curdlan gum-PEGamine nanoparticles (FA-Py-CG-PEGamine NPs). The results of physicochemical properties revealed that the fabricated FA-Py-CG-PEGamine NPs were between 100 and 400 nm in size with a majorly spherical shaped, crystalline nature, and the encapsulation efficiency and loading capacity were 79.04 ± 0.79 %, and 8.12 ± 0.39 % respectively. The drug release rate was significantly higher at pH 5.4 (80.14 ± 0.79 %) compared to pH 7.2. The cytotoxic potential of FA-Py-CG-PEGamine NPs against MCF-7 cells potentially reduced the number of cells after 24 h with 42.27 μg × mL-1 as IC50 value. The higher intracellular accumulation of pyrimidine-2(5H)-thione in MCF-7 cells leads to apoptosis, observed by AO/EBr staining and flow cytometry analysis. The highest pyrimidine-2(5H)-thione internalization in MCF-7 cells may be due to folate conjugated on the surface of curdlan gum nanoparticles. Further, internalized pyrimidine-2(5H)-thione increases the intracellular ROS level, leading to apoptosis and inducing the decalin in mitochondrial membrane potential. These outcomes demonstrated that the FA-Py-CG-PEGamine NPs were specificity-targeting folate receptors on the plasma membranes of MCF-7 Cells.
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Affiliation(s)
- Selvaraj Kunjiappan
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamilnadu, India.
| | - Theivendren Panneerselvam
- Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Namakkal 637205, Tamilnadu, India
| | - Parasuraman Pavadai
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India
| | - Vanavil Balakrishnan
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamilnadu, India
| | - Sureshbabu Ram Kumar Pandian
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamilnadu, India
| | - Ponnusamy Palanisamy
- School of Mechanical Engineering, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India
| | - Murugesan Sankaranarayanan
- Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani Campus, Pilani-333031, Rajasthan, India
| | | | - Ganeshraja Ayyakannu Sundaram
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Poonamallee High Road, Chennai 600 077, Tamilnadu, India
| | - Wei-Lung Tseng
- Department of Chemistry, National Sun Yat-sen University, No. 70, Lien-hai Road, Gushan District, Kaohsiung city 80424, Taiwan; School of Pharmacy, Kaohsiung Medical University, No. 100, Shiquan 1st Road, Sanmin District, Kaohsiung city 80708, Taiwan
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Reno A, Tang J, Sudbeck M, Custodio PF, Baldus B, McLaughlin E, Peng F, Xiao H. Evaluation of a Deep Learning Based Approach to Computational Label Free Cell Viability Quantification. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.29.610252. [PMID: 39257757 PMCID: PMC11383692 DOI: 10.1101/2024.08.29.610252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2024]
Abstract
One of the most common techniques found in a cell biology or tissue engineering lab is the cytotoxicity assay. This can be performed using a variety of different dyes and stains and various protocols to result in a clear indication of dead and live cells within a culture to quantify the viability of a culture and monitor for sudden drops or increases in viability by a drug, material, viral vector, etc introduced into the culture. This assay helps cell biologists determine the health of their culture and what toxicity added substances may add to the culture and whether they are appropriate and safe to use with human cells. However, many of the dyes and stains used for this process are eventually toxic to cells, rendering the cells useless after testing and preventing real time monitoring of the same culture over a period of hours or days. Computation biology is moving cell biology towards novel and innovative techniques such as in silico labeling and dye free labeling using deep learning algorithms. In this work, we investigate whether it is feasible to train a Resnet CNN model to detect morphological changes in human cells that indicate cell death in order to classify cells as live or dead without utilizing a stain or dye. This work also aims to train one CNN model to count all cells regardless of viability status to get a total cell count, and then one CNN model that specifically identifies and counts all of the dead cells for an accurate dead and live cell total by utilizing both pieces of data to determine a general viability percentage for the culture. Additionally, this work explores the use of various image enhancements to understand if this process helps or impedes the deep learning models in their detection of total cells and dead cells.
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Affiliation(s)
- Allison Reno
- Department of Bioengineering, Clemson University, Clemson, SC, USA
| | - Jianan Tang
- Holcombe Department of Electrical and Computer Engineering, Clemson University, Clemson, SC, USA
| | - Madeline Sudbeck
- Department of Biological Sciences, Clemson University, Clemson, SC, USA
| | | | - Brandi Baldus
- Department of Materials Science and Engineering, Clemson University, Clemson, SC, USA
| | | | - Fei Peng
- Department of Materials Science and Engineering, Clemson University, Clemson, SC, USA
| | - Hai Xiao
- Holcombe Department of Electrical and Computer Engineering, Clemson University, Clemson, SC, USA
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Abd-Elkareem M, Alnasser SM, Meshal A, Abdullah RI, Ali AU. The effect of Norethisterone acetate on the uterus of albino rats: histological, histochemical and ultrastructure study. BMC Vet Res 2024; 20:384. [PMID: 39210341 PMCID: PMC11360500 DOI: 10.1186/s12917-024-04219-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Norethisterone acetate (NETA), also known as norethindrone acetate is a progestogens medication that is widely used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders as abnormal uterine bleeding and endometriosis. There is a lack of detailed histological information regarding the effects of NETA on the uterine structure. So, the present study focuses on the uterine histological, histochemical and ultrastructure changes following the exposure to NETA in the albino rats. To do this aim, fourteen adult female albino rats were used. They were randomly divided into two equally groups: Control group and NETA treated group. Albino rats of control group were administered daily food, water and orally distilled water only, while rats of NETA treated group were administered daily orally 20 µg of NETA dissolved in 2 ml distilled water, food, and water. The experiment was continued for three weeks. RESULTS The findings of the present work indicated that the use of NETA has negative effects on the endometrial epithelium (proliferation, autophagy and apoptosis), glands (necrotic, apoptotic or pseudosecretory glands) and stromal and myometrial reactions (granulocytes, connective tissue remodeling, apoptosis, myocytes hypertrophy). CONCLUSION This work revealed that NETA has desynchronized progestogenic effect on the uterine tissues of the albino rat and thereby prevent implantation and pregnancy.
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Affiliation(s)
- Mahmoud Abd-Elkareem
- Department of Cell and Tissues, Faculty of Veterinary Medicine, Assiut University, Assiut, 71526, Egypt.
| | - Sulaiman Mohammed Alnasser
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia
| | - Alotaibi Meshal
- Pharmacy practice, College of pharmacy, University of Hafr Albatin, Hafr Albatin, Saudi Arabia
| | - Raghda Ismail Abdullah
- Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, New Valley University, El Kharga, Egypt
| | - Ahmed U Ali
- Department of Pharmaceutics, Faculty of Pharmacy, Merit University, Sohag, Egypt
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Liu W, Liu L, Li H, Xie Y, Bai J, Guan J, Qi H, Sun J. Targeted pathophysiological treatment of ischemic stroke using nanoparticle-based drug delivery system. J Nanobiotechnology 2024; 22:499. [PMID: 39164747 PMCID: PMC11337765 DOI: 10.1186/s12951-024-02772-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 08/14/2024] [Indexed: 08/22/2024] Open
Abstract
Ischemic stroke poses significant challenges in terms of mortality and disability rates globally. A key obstacle to the successful treatment of ischemic stroke lies in the limited efficacy of administering therapeutic agents. Leveraging the unique properties of nanoparticles for brain targeting and crossing the blood-brain barrier, researchers have engineered diverse nanoparticle-based drug delivery systems to improve the therapeutic outcomes of ischemic stroke. This review provides a concise overview of the pathophysiological mechanisms implicated in ischemic stroke, encompassing oxidative stress, glutamate excitotoxicity, neuroinflammation, and cell death, to elucidate potential targets for nanoparticle-based drug delivery systems. Furthermore, the review outlines the classification of nanoparticle-based drug delivery systems according to these distinct physiological processes. This categorization aids in identifying the attributes and commonalities of nanoparticles that target specific pathophysiological pathways in ischemic stroke, thereby facilitating the advancement of nanomedicine development. The review discusses the potential benefits and existing challenges associated with employing nanoparticles in the treatment of ischemic stroke, offering new perspectives on designing efficacious nanoparticles to enhance ischemic stroke treatment outcomes.
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Affiliation(s)
- Wei Liu
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Lubin Liu
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Hong Li
- Clinical Laboratory, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital), Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266033, China
| | - Yutong Xie
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Ju Bai
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Jialiang Guan
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Hongzhao Qi
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China.
| | - Jinping Sun
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
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11
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Wang H, Kobayashi H, Shimada K, Oura S, Oyama Y, Kitakaze H, Noda T, Yabuta N, Miyata H, Ikawa M. MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice. J Cell Sci 2024; 137:jcs261962. [PMID: 39092789 PMCID: PMC11385322 DOI: 10.1242/jcs.261962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024] Open
Abstract
The structure of the sperm flagellar axoneme is highly conserved across species and serves the essential function of generating motility to facilitate the meeting of spermatozoa with the egg. During spermiogenesis, the axoneme elongates from the centrosome, and subsequently the centrosome docks onto the nuclear envelope to continue tail biogenesis. Mycbpap is expressed predominantly in mouse and human testes and conserved in Chlamydomonas as FAP147. A previous cryo-electron microscopy analysis has revealed the localization of FAP147 to the central apparatus of the axoneme. Here, we generated Mycbpap-knockout mice and demonstrated the essential role of Mycbpap in male fertility. Deletion of Mycbpap led to disrupted centrosome-nuclear envelope docking and abnormal flagellar biogenesis. Furthermore, we generated transgenic mice with tagged MYCBPAP, which restored the fertility of Mycbpap-knockout males. Interactome analyses of MYCBPAP using Mycbpap transgenic mice unveiled binding partners of MYCBPAP including central apparatus proteins, such as CFAP65 and CFAP70, which constitute the C2a projection, and centrosome-associated proteins, such as CCP110. These findings provide insights into a MYCBPAP-dependent regulation of the centrosome-nuclear envelope docking and sperm tail biogenesis.
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Affiliation(s)
- Haoting Wang
- Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Hiroko Kobayashi
- Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Keisuke Shimada
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Seiya Oura
- Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Yuki Oyama
- Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Hiroaki Kitakaze
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
| | - Taichi Noda
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan
- Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto, Kumamoto 860-8555, Japan
| | - Norikazu Yabuta
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Haruhiko Miyata
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
| | - Masahito Ikawa
- Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
- The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
- Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
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12
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Qin LT, Lei YX, Liu M, Zeng HH, Liang YP, Mo LY. Toxic interactions at the physiological and biochemical levels of green algae under stress of mixtures of three azole fungicides. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 926:171771. [PMID: 38521260 DOI: 10.1016/j.scitotenv.2024.171771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/27/2024] [Accepted: 03/15/2024] [Indexed: 03/25/2024]
Abstract
Assessing the interactions between environmental pollutants and these mixtures is of paramount significance in understanding their negative effects on aquatic ecosystems. However, existing research often lacks comprehensive investigations into the physiological and biochemical mechanisms underlying these interactions. This study aimed to reveal the toxic mechanisms of cyproconazole (CYP), imazalil (IMA), and prochloraz (PRO) and corresponding these mixtures on Auxenochlorella pyrenoidosa by analyzing the interactions at physiological and biochemical levels. Higher concentrations of CYP, IMA, and PRO and these mixtures resulted in a reduction in chlorophyll (Chl) content and increased total protein (TP) suppression, and malondialdehyde (MDA) content exhibited a negative correlation with algal growth. The activity of catalase (CAT) and superoxide dismutase (SOD) decreased with increasing azole fungicides and their mixture concentrations, correlating positively with growth inhibition. Azole fungicides induced dose-dependent apoptosis in A. pyrenoidosa, with higher apoptosis rates indicative of greater pollutant toxicity. The results revealed concentration-dependent toxicity effects, with antagonistic interactions at low concentrations and synergistic effects at high concentrations within the CYP-IMA mixtures. These interactions were closely linked to the interactions observed in Chl-a, carotenoid (Car), CAT, and cellular apoptosis. The antagonistic effects of CYP-PRO mixtures on A. pyrenoidosa growth inhibition can be attributed to the antagonism observed in Chl-a, Chl-b, Car, TP, CAT, SOD, and cellular apoptosis. This study emphasized the importance of gaining a comprehensive understanding of the physiological and biochemical interactions within algal cells, which may help understand the potential mechanism of toxic interaction.
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Affiliation(s)
- Li-Tang Qin
- College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China; Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin 541004, China; Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541004, China
| | - Yu-Xue Lei
- College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China
| | - Min Liu
- College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China
| | - Hong-Hu Zeng
- College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China; Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin 541004, China; Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541004, China
| | - Yan-Peng Liang
- College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China; Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin 541004, China; Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541004, China.
| | - Ling-Yun Mo
- Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin 541004, China; Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541004, China; Technical Innovation Center of Mine Geological Environmental Restoration Engineering in Southern Karst Area, Nanjing, China.
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13
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Abdullah M, Ehaideb S, Roberts G, Bouchama A. Insights into pathophysiology and therapeutic strategies for heat stroke: Lessons from a baboon model. Exp Physiol 2024; 109:484-501. [PMID: 38124439 PMCID: PMC10988686 DOI: 10.1113/ep091586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/04/2023] [Indexed: 12/23/2023]
Abstract
Heat stroke is a perilous condition marked by severe hyperthermia and extensive multiorgan dysfunction, posing a considerable risk of mortality if not promptly identified and treated. Furthermore, the complex biological mechanisms underlying heat stroke-induced tissue and cell damage across organ systems remain incompletely understood. This knowledge gap has hindered the advancement of effective preventive and therapeutic strategies against this condition. In this narrative review, we synthesize key insights gained over a decade using a translational baboon model of heat stroke. By replicating heat stroke pathology in a non-human primate species that closely resembles humans, we have unveiled novel insights into the pathways of organ injury and cell death elicited by this condition. Here, we contextualize and integrate the lessons learned concerning heat stroke pathophysiology and recovery, areas that are inherently challenging to investigate directly in human subjects. We suggest novel research directions to advance the understanding of the complex mechanisms underlying cell death and organ injury. This may lead to precise therapeutic strategies that benefit individuals suffering from this debilitating condition.
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Affiliation(s)
- Mashan Abdullah
- Experimental Medicine Department, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical CityMinistry of National Guard Health AffairsRiyadhSaudi Arabia
| | - Salleh Ehaideb
- Experimental Medicine Department, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical CityMinistry of National Guard Health AffairsRiyadhSaudi Arabia
| | - George Roberts
- Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
| | - Abderrezak Bouchama
- Experimental Medicine Department, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical CityMinistry of National Guard Health AffairsRiyadhSaudi Arabia
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14
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Taatjes DJ, Roth J. In focus in HCB. Histochem Cell Biol 2024; 161:207-209. [PMID: 38416164 DOI: 10.1007/s00418-024-02271-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Affiliation(s)
- Douglas J Taatjes
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
| | - Jürgen Roth
- University of Zurich, CH-8091, Zurich, Switzerland
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15
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Holota R, Dečmanová V, Alexovič Matiašová A, Košuth J, Slovinská L, Pačut L, Tomori Z, Daxnerová Z, Ševc J. Cleaved caspase-3 is present in the majority of glial cells in the intact rat spinal cord during postnatal life. Histochem Cell Biol 2024; 161:269-286. [PMID: 37938347 PMCID: PMC10912154 DOI: 10.1007/s00418-023-02249-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/11/2023] [Indexed: 11/09/2023]
Abstract
Cell death is an essential process that occurs during the development of the central nervous system. Despite the availability of a wide range of commercially produced antibodies against various apoptotic markers, data regarding apoptosis in intact spinal cord during postnatal development and adulthood are mostly missing. We investigated apoptosis in rat spinal cord at different stages of ontogenesis (postnatal days 8, 29, and 90). For this purpose, we applied immunofluorescent detection of two widely used apoptotic markers, cleaved caspase-3 (cC3) and cleaved poly(ADP-ribose) polymerase (cPARP). Surprisingly, we found significant discrepancy between the number of cC3+ cells and PARP+ cells, with a ratio between 500:1 and 5000:1 in rat spinal cord at all postnatal time points. The majority of cC3+ cells were glial cells and did not exhibit an apoptotic phenotype. In contrast with in vivo results, in vitro analysis of primary cell cultures derived from neonatal rat spinal cord and treated with the apoptotic inductor staurosporine revealed a similar onset of occurrence of both cC3 and cPARP in cells subjected to apoptosis. Gene expression analysis of spinal cord revealed elevated expression of the Birc4 (XIAP), Birc2, and Birc5 (Survivin) genes, which are known potent inhibitors of apoptosis. Our data indicate that cC3 is not an exclusive marker of apoptosis, especially in glial cells, owing its possible presence in inhibited forms and/or its participation in other non-apoptotic roles. Therefore, cPARP appears to be a more appropriate marker to detect apoptosis.
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Affiliation(s)
- R Holota
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
| | - V Dečmanová
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
| | - A Alexovič Matiašová
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic.
| | - J Košuth
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
| | - L Slovinská
- Associated Tissue Bank, Faculty of Medicine, P. J. Šafárik University in Košice and L. Pasteur University Hospital, Tr. SNP 1, 04011, Košice, Slovak Republic
- Department of Regenerative Medicine and Cell Therapy, Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 04001, Košice, Slovak Republic
| | - L Pačut
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
| | - Z Tomori
- Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 04001, Košice, Slovak Republic
| | - Z Daxnerová
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
| | - J Ševc
- Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Šrobárova 2, 04154, Košice, Slovak Republic
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16
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Jeon SJ, Choi EY, Han EJ, Lee SW, Moon JM, Jung SH, Jung JY. Piperlongumine induces apoptosis via the MAPK pathway and ERK‑mediated autophagy in human melanoma cells. Int J Mol Med 2023; 52:115. [PMID: 37830157 PMCID: PMC10599349 DOI: 10.3892/ijmm.2023.5318] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 09/21/2023] [Indexed: 10/14/2023] Open
Abstract
Piperlongumine (PL) is an amide alkaloid with diverse pharmacological effects against cancer, bronchitis and asthma; however, research on its efficacy against melanoma is lacking. The present study investigated the anticancer effects of PL on A375SM and A375P human melanoma cells. PL decreased the survival rate of A375SM and A375P cells, as shown by MTT assay, increase of apoptotic cells by DAPI staining. And PL induced apoptosis by decreasing the expression of the anti‑apoptotic protein Bcl‑2 and increasing that of the pro‑apoptotic proteins cleaved‑PARP and Bax. PL also induced apoptosis in A375SM and A375P cells via the MAPK pathway, increasing expression of the MAPK pathway proteins, phosphorylated‑(p‑ERK), p‑JNK p‑p38. These proteins were confirmed by western blot. In addition, A375SM and A375P cells treated with PL showed an increased number of acidic vesicular organelles by acridine orange staining. Also, autophagy induced by the expression of 1A/1B‑light chain 3, Beclin 1and mTOR was investigated through western blot. When PL was applied following treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine, autophagy exhibited a cytoprotective effect against apoptosis in MTT assay. Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.
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Affiliation(s)
- Su-Ji Jeon
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Eun-Young Choi
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Eun-Ji Han
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Sang-Woo Lee
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Jun-Mo Moon
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Soo-Hyun Jung
- Department of Companion and Laboratory Animal Science, Kongju National University
| | - Ji-Youn Jung
- Department of Companion and Laboratory Animal Science, Kongju National University
- Research Institute for Natural Products, Kongju National University
- Research Center of Crop Breeding for Omics and Artificial Intelligence, Kongju National University, Yesan-eup, Chungcheongnam-do 32439, Republic of Korea
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17
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Li Y, Pavanram P, Bühring J, Rütten S, Schröder KU, Zhou J, Pufe T, Wang LN, Zadpoor AA, Jahr H. Physiomimetic biocompatibility evaluation of directly printed degradable porous iron implants using various cell types. Acta Biomater 2023; 169:589-604. [PMID: 37536493 DOI: 10.1016/j.actbio.2023.07.056] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 07/04/2023] [Accepted: 07/27/2023] [Indexed: 08/05/2023]
Abstract
Additively manufactured (AM) degradable porous metallic biomaterials offer unique opportunities for satisfying the design requirements of an ideal bone substitute. Among the currently available biodegradable metals, iron has the highest elastic modulus, meaning that it would benefit the most from porous design. Given the successful preclinical applications of such biomaterials for the treatment of cardiovascular diseases, the moderate compatibility of AM porous iron with osteoblast-like cells, reported in earlier studies, has been surprising. This may be because, as opposed to static in vitro conditions, the biodegradation products of iron in vivo are transported away and excreted. To better mimic the in situ situations of biodegradable biomaterials after implantation, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static conditions to the conditions with dynamic in situ-like fluid flow perfusion in a bioreactor. Furthermore, the compatibility of these scaffolds with four different cell types was evaluated to better understand the implications of these implants for the complex process of natural wound healing. These included endothelial cells, L929 fibroblasts, RAW264.7 macrophage-like cells, and osteoblastic MG-63 cells. The biodegradation rate of the scaffolds was significantly increased in the perfusion bioreactor as compared to static immersion. Under either condition, the compatibility with L929 cells was the best. Moreover, the compatibility with all the cell types was much enhanced under physiomimetic dynamic flow conditions as compared to static biodegradation. Our study highlights the importance of physiomimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro. STATEMENT OF SIGNIFICANCE: Additively manufactured (AM) degradable porous metals offer unique opportunities for the treatment of large bony defects. Despite the successful preclinical applications of biodegradable iron in the cardiovascular field, the moderate compatibility of AM porous iron with osteoblast-like cells was reported. To better mimic the in vivo condition, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static condition to dynamic perfusion. Furthermore, the compatibility of these scaffolds with various cell types was evaluated to better simulate the process of natural wound healing. Our study suggests that AM porous iron holds great promise for orthopedic applications, while also highlighting the importance of physio-mimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro.
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Affiliation(s)
- Y Li
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China; Department of Biomechanical Engineering, Delft University of Technology, Delft 2628CD, the Netherlands.
| | - P Pavanram
- Institute of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - J Bühring
- Institute of Structural Mechanics and Lightweight Design, RWTH Aachen University, 52062 Aachen, Germany
| | - S Rütten
- Institute of Pathology, Electron Microscopy Unit, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - K-U Schröder
- Institute of Structural Mechanics and Lightweight Design, RWTH Aachen University, 52062 Aachen, Germany
| | - J Zhou
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628CD, the Netherlands
| | - T Pufe
- Institute of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - L-N Wang
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
| | - A A Zadpoor
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628CD, the Netherlands
| | - H Jahr
- Institute of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany.; Institute of Structural Mechanics and Lightweight Design, RWTH Aachen University, 52062 Aachen, Germany.
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18
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Perrotta I. Seeing beyond apoptosis: ultrastructural aspects of necrosis in human atherosclerosis. Cardiovasc Pathol 2023; 66:107560. [PMID: 37453592 DOI: 10.1016/j.carpath.2023.107560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/11/2023] [Accepted: 07/11/2023] [Indexed: 07/18/2023] Open
Abstract
In recent years, there has been an explosive growth of research to decipher the pathobiologic relevance of cell death in the development and progression of various cardiovascular disorders such as arterial remodeling and atherosclerosis. High rates of cell death have been reported in animal models, particularly following balloon catheter injury. Also, in humans there is considerable evidence indicating a close connection between cell death and atherosclerosis. In this regard, diverse biochemical and molecular analysis have suggested that intraplaque cells preferentially die by apoptosis, a mode of cell death considered to be active, highly regulated and programmed. In contrast to apoptosis, necrosis has been classically defined as an uncontrolled form of cell death that can occur in response to chemical or physical insults such as trauma, infection, toxins, or lack of blood supply. Necrosis has long been known to be present within atherosclerotic plaques but to date it is still less well understood and characterized than apoptosis. In addition, although electron microscopy (EM) remains essential in cell death research, only a very small proportion of studies deal with the ultrastructural aspects of cell death and/or include EM images to support their findings. As a consequence, many features of cell death modes in human atherosclerosis have not yet been thoroughly investigated and defined. The present study was undertaken to provide an ultrastructural description of the route/s by which intraplaque cells can die also suggesting novel insights for future research.
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Affiliation(s)
- Ida Perrotta
- Department of Biology, Ecology and Earth Sciences, Centre for Microscopy and Microanalysis, University of Calabria, Arcavacata di Rende, Cosenza 87036, Italy.
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19
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Motta JVDO, Carneiro LS, Martínez LC, Bastos DSS, Resende MTCS, Castro BMC, Neves MM, Zanuncio JC, Serrão JE. Midgut Cell Damage and Oxidative Stress in Partamona helleri (Hymenoptera: Apidae) Workers Caused by the Insecticide Lambda-Cyhalothrin. Antioxidants (Basel) 2023; 12:1510. [PMID: 37627505 PMCID: PMC10451733 DOI: 10.3390/antiox12081510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/19/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
The stingless bee Partamona helleri plays a role in pollinating both native and cultivated plants in the Neotropics. However, its populations can be reduced by the pyrethroid insecticide lambda-cyhalothrin. This compound may cross the intestinal barrier and circulate through the hemolymph, affecting various non-target bee organs. The aim of the present study was to assess the extent of cellular damage in the midgut and the resulting oxidative stress caused by lambda-cyhalothrin in P. helleri workers. Bees were orally exposed to lambda-cyhalothrin. The lethal concentration at which 50% of the bees died (LC50) was 0.043 mg a.i. L-1. The P. helleri workers were fed this concentration of lambda-cyhalothrin and their midguts were evaluated. The results revealed signs of damage in the midgut epithelium, including pyknotic nuclei, cytoplasm vacuolization, changes in the striated border, and the release of cell fragments, indicating that the midgut was compromised. Furthermore, the ingestion of lambda-cyhalothrin led to an increase in the activity of the detoxification enzyme superoxide dismutase and the levels of the NO2/NO3 markers, indicating oxidative stress. Conversely, the activities of the catalase and glutathione S-transferase enzymes decreased, supporting the occurrence of oxidative stress. In conclusion, the ingestion of lambda-cyhalothrin by P. helleri workers resulted in damage to their midguts and induced oxidative stress.
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Affiliation(s)
- João Victor de Oliveira Motta
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
| | - Lenise Silva Carneiro
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
| | | | - Daniel Silva Sena Bastos
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
| | - Matheus Tudor Candido Santos Resende
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
| | - Bárbara Monteiro Castro Castro
- Department of Entomology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (B.M.C.C.); (J.C.Z.)
| | - Mariana Machado Neves
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
| | - José Cola Zanuncio
- Department of Entomology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (B.M.C.C.); (J.C.Z.)
| | - José Eduardo Serrão
- Department of General Biology, Institute of Biotechnology Applied to Agriculture, Federal University of Viçosa, Viçosa 36570-900, Brazil; (J.V.d.O.M.); (L.S.C.); (D.S.S.B.); (M.T.C.S.R.); (M.M.N.)
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20
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Zsiros V, Dóczi N, Petővári G, Pop A, Erdei Z, Sebestyén A, L Kiss A. BMP-induced non-canonical signaling is upregulated during autophagy-mediated regeneration in inflamed mesothelial cells. Sci Rep 2023; 13:10426. [PMID: 37369758 PMCID: PMC10300029 DOI: 10.1038/s41598-023-37453-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 06/22/2023] [Indexed: 06/29/2023] Open
Abstract
Previously, we showed that after Freund's adjuvant-induced peritonitis, rat mesothelial cells regain their epithelial phenotype through mesenchymal-epithelial transition (MET) accompanied by autophagy. Since bone morphogenetic proteins (BMPs) are well-known MET-inducers, we were interested in the potential expression of BMPs and BMP-induced pathways. Although mesothelial cells expressed lower amounts of BMP7, its level in the peritoneal cavity and mesothelial synthesis of BMP4 were significantly increased during inflammation. BMPR1A and BMPR2 were also significantly expressed. Expression of transforming growth factor beta-activated kinase (TAK1) and c-Jun NH2-terminal kinases (JNK1-JNK2) were more intense than that of phosphorylated Mothers Against Decapentaplegic homolog 1/5 (p-SMAD1/5), confirming that the non-canonical pathway of BMPs prevailed in our model. JNK signaling through B-cell lymphoma-2 (Bcl-2) can contribute to Beclin-1 activation. We demonstrated that TAK1-JNK-Bcl-2 signaling was upregulated simultaneously with the autophagy-mediated regeneration. A further goal of our study was to prove the regenerative role of autophagy after inflammation. We used a specific inhibitor, bafilomycin A1 (BafA1), and found that BafA1 treatment decreased the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3B) and resulted in morphological signs of cell death in inflamed mesothelial cells indicating that if autophagy is arrested, regeneration turns into cell death and consequently, mesothelial cells die.
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Affiliation(s)
- Viktória Zsiros
- Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Tűzoltó u. 58., Budapest, 1094, Hungary.
| | - Nikolett Dóczi
- Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Tűzoltó u. 58., Budapest, 1094, Hungary
| | - Gábor Petővári
- Department of Pathology and Experimental Cancer Research, Semmelweis University Budapest, Üllői út 26., Budapest, 1085, Hungary
| | - Alexandra Pop
- Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Tűzoltó u. 58., Budapest, 1094, Hungary
| | - Zsófia Erdei
- Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Tűzoltó u. 58., Budapest, 1094, Hungary
| | - Anna Sebestyén
- Department of Pathology and Experimental Cancer Research, Semmelweis University Budapest, Üllői út 26., Budapest, 1085, Hungary
| | - Anna L Kiss
- Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Tűzoltó u. 58., Budapest, 1094, Hungary
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21
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Arafa KK, Ibrahim A, Mergawy R, El-Sherbiny IM, Febbraio F, Hassan RYA. Advances in Cancer Diagnosis: Bio-Electrochemical and Biophysical Characterizations of Cancer Cells. MICROMACHINES 2022; 13:mi13091401. [PMID: 36144024 PMCID: PMC9504238 DOI: 10.3390/mi13091401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 05/09/2023]
Abstract
Cancer is a worldwide leading cause of death, and it is projected that newly diagnosed cases globally will reach 27.5 million each year by 2040. Cancers (malignant tumors), unlike benign tumors are characterized by structural and functional dedifferentiation (anaplasia), breaching of the basement membrane, spreading to adjacent tissues (invasiveness), and the capability to spread to distant sites (metastasis). In the cancer biology research field, understanding and characterizing cancer metastasis as well as features of cell death (apoptosis) is considered a technically challenging subject of study and clinically is very critical and necessary. Therefore, in addition to the cytochemical methods traditionally used, novel biophysical and bioelectrochemical techniques (e.g., cyclic voltammetry and electrochemical impedance spectroscopy), atomic force microscopy, and electron microscopic methods are increasingly being deployed to better understand these processes. Implementing those methods at the preclinical level enables the rapid screening of new anticancer drugs with understanding of their central mechanism for cancer therapy. In this review, principles and basic concepts of new techniques suggested for metastasis, and apoptosis examinations for research purposes are introduced, along with examples of each technique. From our recommendations, the privilege of combining the bio-electrochemical and biosensing techniques with the conventional cytochemical methods either for research or for biomedical diagnosis should be emphasized.
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Affiliation(s)
- Kholoud K. Arafa
- Nanoscience Program, University of Science and Technology (UST), Zewail City of Science and Technology, Giza 12578, Egypt
| | - Alaa Ibrahim
- Nanoscience Program, University of Science and Technology (UST), Zewail City of Science and Technology, Giza 12578, Egypt
| | - Reem Mergawy
- Nanoscience Program, University of Science and Technology (UST), Zewail City of Science and Technology, Giza 12578, Egypt
| | - Ibrahim M. El-Sherbiny
- Nanoscience Program, University of Science and Technology (UST), Zewail City of Science and Technology, Giza 12578, Egypt
| | - Ferdinando Febbraio
- Institute of Biochemistry and Cell Biology, National Research Council (CNR), Via P. Castellino 111, 80131 Naples, Italy
| | - Rabeay Y. A. Hassan
- Nanoscience Program, University of Science and Technology (UST), Zewail City of Science and Technology, Giza 12578, Egypt
- Correspondence: ; Tel.: +20-1129216152
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22
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Jahanbani F, Maynard RD, Sing JC, Jahanbani S, Perrino JJ, Spacek DV, Davis RW, Snyder MP. Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study. PLoS One 2022; 17:e0272703. [PMID: 35943990 PMCID: PMC9362953 DOI: 10.1371/journal.pone.0272703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects-one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients' immune cells and suggest new insights into ME/CFS biology.
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Affiliation(s)
- Fereshteh Jahanbani
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
| | - Rajan D. Maynard
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
| | - Justin Cyril Sing
- Department of Molecular Genetics, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
| | - Shaghayegh Jahanbani
- Division of Immunology and Rheumatology, Stanford University School of Medicine, and VA Palo Alto Health Care System, Palo Alto, California, United States of America
| | - John J. Perrino
- Stanford Cell Sciences Imaging Facility (CSIF), Stanford University School of Medicine Stanford, Stanford, California, United States of America
| | - Damek V. Spacek
- Karius Incorporated, Redwood City, California, United States of America
| | - Ronald W. Davis
- ME/CFS Collaborative Research Center at Stanford, Stanford Genome Technology Center, Stanford University School of Medicine, Palo Alto, California, United States of America
| | - Michael P. Snyder
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
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23
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Ovidi E, Laghezza Masci V, Taddei AR, Torresi J, Tomassi W, Iannone M, Tiezzi A, Maggi F, Garzoli S. Hemp (Cannabis sativa L., Kompolti cv.) and Hop (Humulus lupulus L., Chinook cv.) Essential Oil and Hydrolate: HS-GC-MS Chemical Investigation and Apoptotic Activity Evaluation. Pharmaceuticals (Basel) 2022; 15:ph15080976. [PMID: 36015124 PMCID: PMC9413834 DOI: 10.3390/ph15080976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/23/2022] [Accepted: 08/02/2022] [Indexed: 12/02/2022] Open
Abstract
In this study, essential oils (EOs) and hydrolates (Hys) from Italian hemp (Cannabis sativa L. Kompolti cv.) and hop (Humulus Lupulus L., Chinook cv.) supply chains were chemically characterized and tested to investigate their apoptotic potential for the first time. Headspace–Gas Chromatography–Mass Spectrometry (HS-GC-MS) techniques were performed to describe their volatile chemical profile, highlighting a composition rich in terpene derivatives such as monoterpenes and sesquiterpenes among which β-myrcene, limonene, β-caryophyllene and α-humulene were the main constituents of EOs; in contrast, linalool, cis-p-menth-2,8-dien-1-ol, terpinen-4-ol, α-terpineol, caryophyllene oxide, and τ-cadinol were found in the Hys. The cytotoxicity activity on human leukemia cells (HL60), human neuroblastoma cells (SH-SY5Y), human metastatic adenocarcinoma breast cells (MCF7), human adenocarcinoma breast cells (MDA), and normal breast epithelial cell (MCF10A) for the EOs and Hys was studied by MTT assay and cytofluorimetric analysis and scanning and transmission electron microscopy were performed to define ultrastructural changes and the mechanism of cells death for HL 60 cells. An induction of the apoptotic mechanism was evidenced for hemp and hop EOs after treatment with the corresponding EC50 dose. In addition, TEM and SEM investigations revealed typical characteristics induced by the apoptotic pathway. Therefore, thanks to the integration of the applied methodologies with the used techniques, this work provides an overview on the metabolomic profile and the apoptotic potential of hemp and hop EOs and, for the first time, also of Hys. The findings of this preliminary study confirm that the EOs and Hys from Cannabis and Humulus species are sources of bioactive molecules with multiple biological effects yet to be explored.
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Affiliation(s)
- Elisa Ovidi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy
| | - Valentina Laghezza Masci
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy
| | | | - Jacopo Torresi
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, 62032 Camerino, Italy
| | - William Tomassi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy
| | - Matteo Iannone
- Circolo ARCI La Staffetta, Via Don Minzoni 29, 56011 Calci, Italy
| | - Antonio Tiezzi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy
| | - Filippo Maggi
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, 62032 Camerino, Italy
| | - Stefania Garzoli
- Department of Chemistry and Technologies of Drug, Sapienza University, 00185 Rome, Italy
- Correspondence:
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24
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Singh H, Singh T, Singh AP, Kaur S, Arora S, Singh B. Hepatoprotective effect of Physalis divaricata in paracetamol induced hepatotoxicity: In vitro, in silico and in vivo analysis. JOURNAL OF ETHNOPHARMACOLOGY 2022; 290:115024. [PMID: 35085744 DOI: 10.1016/j.jep.2022.115024] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 09/27/2021] [Accepted: 01/18/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Physalis divaricata D. Don. is an erect weed of family Solanaceae. The root extract of this plant is used by the indigenous communities of Sub-Himalayan region of Uttarakhand, India for the treatment of liver disorders. AIM OF THE STUDY To evaluate hepatoprotective potential of P. divaricata in paracetamol (PCM) induced hepatotoxicity in rats. MATERIALS AND METHODS The dried roots of P. divaricata were subjected to extraction using different solvents. The chloroform extract, methanol extract and bioactive aqueous fraction of methanol extract were evaluated for hepatoprotective effect. After initial in vitro screening, all extracts were screened for hepatoprotective potential in PCM (3 g/kg p.o) induced hepatotoxicity. Following PCM administration, extracts were administered orally for 7 days in increasing dose concentrations. All the animals were euthanized on eighth day, serum and liver tissues were collected and subjected to various biochemical and histopathological analysis. Aqueous fraction of methanol extract was further analyzed using LC- MS analysis. RESULTS Methanol extract and its bioactive aqueous fraction exhibited significant and better in vitro antioxidant and antiproliferative activity as compared to chloroform extract. PCM treatment caused hepatotoxicity as assessed by altered levels of various hepatic biomarkers (increase in the levels of ALT, AST, ALP, albumin, triglycerides, cholesterol, TBARS, and AOPPs as well as decrease in GSH and TrxR levels) along with histopathological changes (portal to portal bridging, necrosis, and inflammation). Methanolic extract (200, 400 and 800 mg/kg) and its aqueous fraction treatment (25, 50 and 100 mg/kg) significantly restored elevated hepatic biomarkers, oxidative stress, and protected normal hepato-architecture. LC-MS analysis of aqueous fraction showed presence of rutin and kaempferol. In silico analysis further showed the capability of rutin to make complex with TNF-α and block its interaction with the target site. CONCLUSION Aqueous fraction showed maximum hepatoprotective potential as conceived through in vitro and in vivo studies. Presence of rutin may explain hepatoprotective potential of P. divaricata.
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Affiliation(s)
- Hasandeep Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
| | - Tanveer Singh
- Department of Neuroscience and Experimental Therapeutics, Texas A&M University, Health Science Center, College of Medicine, Bryan, TX, 77807, USA.
| | - Amrit Pal Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
| | - Sarabjit Kaur
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
| | - Saroj Arora
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
| | - Balbir Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
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25
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Wang XR, Shao Y, Wang C, Liu YQ. Effects of heat stress on virus transmission and virus-mediated apoptosis in whitefly Bemisia tabaci. ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY 2022; 110:e21857. [PMID: 34859483 DOI: 10.1002/arch.21857] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/11/2021] [Accepted: 11/15/2021] [Indexed: 06/13/2023]
Abstract
Tomato yellow leaf curl virus (TYLCV), a plant DNA virus of the genus Begomovirus, is transmitted by whiteflies of the Bemisia tabaci species complex in a persistent manner. Our previous study indicated that activation of the apoptosis pathway in whiteflies could facilitate TYLCV accumulation and transmission. Considering that temperature change can influence the spread of insect-borne plant viruses, we focused on plant virus induced-apoptosis to investigate the underlying mechanism of temperature regulation on plant virus transmission via an insect vector. We found that heat stress (40°C) on whiteflies could facilitate TYLCV accumulation and increase transmission to tomato plants. Despite upregulation of caspase-1 and caspase-3 gene expression, heat stress failed to induce an increase in the activation of cleaved caspase-3 and DNA fragmentation in TYLCV-infected whiteflies. However, our data failed to determine the role of heat stress in apoptosis modulation of insect-plant virus interplay while still providing clues to understand insect vectors and their transmitted plant viruses.
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Affiliation(s)
- Xin-Ru Wang
- Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province; Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Entomology, University of Minnesota, St. Paul, Minnesota, USA
| | - Yue Shao
- Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province; Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, China
- The Plant Protection and Soil Fertilizer Management Station of Wenzhou, Wenzhou, Zhejiang, China
| | - Chao Wang
- Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province; Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yin-Quan Liu
- Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province; Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, China
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26
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Kabir MA, Kharel A, Malla S, Kreis ZJ, Nath P, Wolfe JN, Hassan M, Kaur D, Sari-Sarraf H, Tiwari AK, Ray A. Automated detection of apoptotic versus nonapoptotic cell death using label-free computational microscopy. JOURNAL OF BIOPHOTONICS 2022; 15:e202100310. [PMID: 34936215 DOI: 10.1002/jbio.202100310] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/09/2021] [Accepted: 12/20/2021] [Indexed: 06/14/2023]
Abstract
Identification of cell death mechanisms, particularly distinguishing between apoptotic versus nonapoptotic pathways, is of paramount importance for a wide range of applications related to cell signaling, interaction with pathogens, therapeutic processes, drug discovery, drug resistance, and even pathogenesis of diseases like cancers and neurogenerative disease among others. Here, we present a novel high-throughput method of identifying apoptotic versus necrotic versus other nonapoptotic cell death processes, based on lensless digital holography. This method relies on identification of the temporal changes in the morphological features of mammalian cells, which are unique to each cell death processes. Different cell death processes were induced by known cytotoxic agents. A deep learning-based approach was used to automatically classify the cell death mechanism (apoptotic vs necrotic vs nonapoptotic) with more than 93% accuracy. This label free approach can provide a low cost (<$250) alternative to some of the currently available high content imaging-based screening tools.
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Affiliation(s)
- Md Alamgir Kabir
- Department of Physics and Astronomy, University of Toledo, Toledo, OH, USA
| | - Ashish Kharel
- Department of Electrical and Computer Science, University of Toledo, Toledo, OH, USA
| | - Saloni Malla
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
| | | | - Peuli Nath
- Department of Physics and Astronomy, University of Toledo, Toledo, OH, USA
| | - Jared Neil Wolfe
- Department of Mechanical Engineering, University of Toledo, Toledo, OH, USA
| | - Marwa Hassan
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
| | - Devinder Kaur
- Department of Electrical and Computer Science, University of Toledo, Toledo, OH, USA
| | - Hamed Sari-Sarraf
- Department of Electrical & Computer Engineering, Texas Tech University, Lubbock, TX, USA
| | - Amit K Tiwari
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
- Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA
| | - Aniruddha Ray
- Department of Physics and Astronomy, University of Toledo, Toledo, OH, USA
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27
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Carneiro LS, Martinez LC, Oliveira AHD, Cossolin JFS, Resende MTCSD, Gonçalves WG, Medeiros-Santana L, Serrão JE. Acute oral exposure to imidacloprid induces apoptosis and autophagy in the midgut of honey bee Apis mellifera workers. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 815:152847. [PMID: 34995599 DOI: 10.1016/j.scitotenv.2021.152847] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/19/2021] [Accepted: 12/28/2021] [Indexed: 06/14/2023]
Abstract
The honey bee Apis mellifera is an important pollinator that increases the yield and quality of crops. In recent years, honey bee populations have declined in some parts of the world, which has been associated with several causes, including pesticides used in agriculture. Neonicotinoids are neurotoxic insecticides widely used in the world with systemic action mode contaminating nectar and pollen that may be consumed by bees. This study evaluated the side effects of imidacloprid in the midgut of A. mellifera after acute oral exposure. Toxicity, histopathology, cytotoxicity, and expression of autophagy-related gene atg1 were evaluated in honey bee workers orally exposed to imidacloprid. The estimated imidacloprid LC50 was 1.44 mg L-1. The midgut epithelium of bees fed on imidacloprid LC50 has the occurrence of cytoplasm vacuoles, enlarged intercellular spaces, disorganization of the striated border, and nuclear pyknosis, with an organ injury index that increases with time exposure. The midgut digestive cells of treated bees have apical protrusions, damaged mitochondria, and autophagosomes that were characterized for content with organelle debris and high expression of atg1. These features indicate the occurrence of high cell death in the midgut of workers exposed to imidacloprid, which may affect the digestibility the physiology of the insect.
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Affiliation(s)
- Lenise Silva Carneiro
- Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais 36570-900, Brazil
| | - Luis Carlos Martinez
- Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais 36570-900, Brazil
| | | | | | | | - Wagner Gonzanga Gonçalves
- Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais 36570-900, Brazil
| | - Luanda Medeiros-Santana
- Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Viçosa - campus Rio Paranaíba, Rio Paranaíba, Minas Gerais 38810-00, Brazil
| | - José Eduardo Serrão
- Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais 36570-900, Brazil.
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28
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Guma E, Bordeleau M, González Ibáñez F, Picard K, Snook E, Desrosiers-Grégoire G, Spring S, Lerch JP, Nieman BJ, Devenyi GA, Tremblay ME, Chakravarty MM. Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment. Proc Natl Acad Sci U S A 2022; 119:e2114545119. [PMID: 35286203 PMCID: PMC8944668 DOI: 10.1073/pnas.2114545119] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 02/01/2022] [Indexed: 12/23/2022] Open
Abstract
Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized; however, less is known about the effects of MIA exposure on embryo development. To address this gap, we performed high-resolution ex vivo MRI to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late-exposed offspring. We further examined the putative neuroanatomical underpinnings of MIA timing in the hippocampus using electron microscopy and identified differential effects due to MIA timing. An increase in apoptotic cell density was observed in the GD9-exposed offspring, while an increase in the density of neurons and glia with ultrastructural features reflective of increased neuroinflammation and oxidative stress was observed in GD17-exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA timing on the earliest stages of neurodevelopment.
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Affiliation(s)
- Elisa Guma
- Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada
- Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada
| | - Maude Bordeleau
- Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada
- Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, QC G1V 4G2, Canada
| | - Fernando González Ibáñez
- Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, QC G1V 4G2, Canada
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
| | - Katherine Picard
- Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, QC G1V 4G2, Canada
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
| | - Emily Snook
- Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada
- Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Gabriel Desrosiers-Grégoire
- Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada
- Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada
| | - Shoshana Spring
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
| | - Jason P. Lerch
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
- Department of Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford OX1 2JD, United Kingdom
| | - Brian J. Nieman
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada
- Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
- Imaging Program, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
| | - Gabriel A. Devenyi
- Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada
- Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada
- Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V8P 5C2, Canada
| | - Marie-Eve Tremblay
- Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, QC G1V 4G2, Canada
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
- Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V8P 5C2, Canada
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 0G4, Canada
| | - M. Mallar Chakravarty
- Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada
- Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada
- Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada
- Department of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, Canada
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Bumiller-Bini Hoch V, Schneider L, Pumpe AE, Lüders E, Hundt JE, Boldt ABW. Marked to Die-Cell Death Mechanisms for Keratinocyte Acantholysis in Pemphigus Diseases. Life (Basel) 2022; 12:life12030329. [PMID: 35330080 PMCID: PMC8948972 DOI: 10.3390/life12030329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/15/2022] [Accepted: 02/18/2022] [Indexed: 11/17/2022] Open
Abstract
Pemphigus is a group of blistering autoimmune diseases causing painful skin lesions, characterized by acantholysis and by the production of autoantibodies against, mainly, adhesion proteins. We reviewed the literature for molecules and/ or features involved in the 12 cell death pathways described by Nomenclature Committee on Cell Death, taking place in pemphigus patients, cell lines, or human skin organ cultures treated with sera or IgG from pemphigus patients or in pemphigus mouse models, and found 61 studies mentioning 97 molecules involved in cell death pathways. Among the molecules, most investigated were pleiotropic molecules such as TNF and CASP3, followed by FASL and CASP8, and then by FAS, BAX, BCL2, and TP53, all involved in more than one pathway but interpreted to function only within apoptosis. Most of these previous investigations focused only on apoptosis, but four recent studies, using TUNEL assays and/or electron microscopy, disqualified this pathway as a previous event of acantholysis. For PV, apoptolysis was suggested as a cell death mechanism based on pathogenic autoantibodies diversity, mitochondrial dysfunction, and p38 MAPK signaling. To answer those many questions that remain on cell death and pemphigus, we propose well-controlled, statistically relevant investigations on pemphigus and cell death pathways besides apoptosis, to overcome the challenges of understanding the etiopathology of pemphigus diseases.
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Affiliation(s)
- Valéria Bumiller-Bini Hoch
- Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba 81531-980, Brazil; (V.B.-B.H.); (L.S.)
- Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil
- Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany; (A.E.P.); (E.L.); (J.E.H.)
| | - Larissa Schneider
- Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba 81531-980, Brazil; (V.B.-B.H.); (L.S.)
| | - Anna Elisabeth Pumpe
- Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany; (A.E.P.); (E.L.); (J.E.H.)
| | - Emelie Lüders
- Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany; (A.E.P.); (E.L.); (J.E.H.)
| | - Jennifer Elisabeth Hundt
- Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany; (A.E.P.); (E.L.); (J.E.H.)
| | - Angelica Beate Winter Boldt
- Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba 81531-980, Brazil; (V.B.-B.H.); (L.S.)
- Correspondence:
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Cytotoxic and Antioxidant Effects of Phoenix dactylifera L. (Ajwa Date Extract) on Oral Squamous Cell Carcinoma Cell Line. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5792830. [PMID: 35233390 PMCID: PMC8882434 DOI: 10.1155/2022/5792830] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/15/2022] [Indexed: 02/06/2023]
Abstract
Aim The aim of the current study is to investigate the antioxidant and apoptotic potential of Ajwa date flesh (ADF) and Ajwa date pit (ADP) extract on human squamous cell carcinoma cell line (HSC-2). Method ADF and ADP were extracted with a solvent extraction method using hexane, acetone, and ethanol, which were then subjected to antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl (DPPH). HSC-2 cells were then treated with different concentrations of ADF and ADP extract for 24, 48, and 72 hours. MTT assay was performed to assess the antiproliferative effect, and Annexin V-FITC was used for the detection of cellular apoptosis. Results Acetone extracts of ADF and ADP had the highest radical scavenging and antioxidant activities followed by the ethanolic extracts, whereas ADP appeared to have significantly higher antioxidant effects than ADF. MTT assay demonstrated that acetone extracts of ADF and ADP were significantly cytotoxic against HSC-2 cells in a dose- and time-dependent manner. The half inhibitory concentration (IC50) of ADF was found to be 8.69 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 50 mg/ml. The IC50 for the ADP was found to be 0.97 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 5 mg/ml. Statistical analysis of the flow cytometry assay showed that the treatment with ADF and ADP extracts had a significant apoptotic effect which occurred in a dose-dependent manner. HSC-2 cells were seen in the late apoptotic stage with higher doses of ADF and ADP extract. ADP extract demonstrated higher apoptotic activity than ADF extract. In addition, combined treatment of ADF and ADP was also performed on HSC-2 cells which demonstrated higher apoptotic activity when compared to the single extract. Conclusion Ajwa date fruit has a promising cytotoxic effect by inhibiting the growth and proliferation of OSCC cells and inducing cell death by apoptosis.
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Sahyon HAE, Ramadan ENM, Althobaiti F, Mashaly MMA. Anti-proliferative effects of the combination of Sulfamethoxazole and Quercetin via caspase3 and NFkB gene regulation: an in vitro and in vivo study. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2022; 395:227-246. [PMID: 34994822 DOI: 10.1007/s00210-021-02174-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/27/2021] [Indexed: 01/30/2023]
Abstract
Combination therapy comprising natural polyphenols and anticancer drugs has been used to decrease the adverse effects and increase the effectiveness and antioxidant activities of the drugs. The antioxidant and anticancer effects of quercetin (Q), a nutritive polyphenol, have been observed both in vitro and in vivo. Likewise, the anticancer activity of sulfamethoxazole (S) has been demonstrated in vitro and in vivo. This study aimed to investigate the in vitro and in vivo anticancer effects of Q alone and in combination with S. The in vitro effects of S, Q, and S + Q on HCT-116, HepG2, MCF-7, and PC3 cell lines were examined. Additionally, the in vivo effects of these drugs were evaluated using Ehrlich ascites carcinoma (EAC) tumor-bearing mice. The in vitro data revealed the potent anticancer activity of S + Q through the induction of apoptosis and cell cycle arrest. The EAC-inoculated mice treated with S + Q presented with elevated SOD, GSH, CAT, and TAC levels and decreased malondialdehyde levels compared with the untreated EAC group, thus revealing the antioxidant and protective actions of S + Q against EAC cell invasion. Furthermore, the downregulation of NFkB and upregulation of the caspase3 gene in the EAC-inoculated mice treated with the S + Q indicated the induction of the apoptotic pathway and decrease in both cell proliferation and metastasis. In conclusion, the combination of S and Q might exert anticancer effects by inducing apoptosis and exhibiting selective toxicity against the cancer cells and thereby protecting the vital organs.
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Affiliation(s)
- Heba Abd Elghany Sahyon
- Chemistry Department, Faculty of Science, Kafrelsheikh University, Elgiesh Street , Kafrelsheikh, 33516, Egypt.
| | - Eman N M Ramadan
- Chemistry Department, Faculty of Science, Damietta University, Damietta, 34518, Egypt
| | - Fayez Althobaiti
- Department of Biotechnology, Collage of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
| | - Mohammad M A Mashaly
- Chemistry Department, Faculty of Science, Damietta University, Damietta, 34518, Egypt
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Wang XR, Cull B. Apoptosis and Autophagy: Current Understanding in Tick–Pathogen Interactions. Front Cell Infect Microbiol 2022; 12:784430. [PMID: 35155277 PMCID: PMC8829008 DOI: 10.3389/fcimb.2022.784430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 01/11/2022] [Indexed: 11/13/2022] Open
Abstract
Tick-borne diseases are a significant threat to human and animal health throughout the world. How tick-borne pathogens successfully infect and disseminate in both their vertebrate and invertebrate hosts is only partially understood. Pathogens have evolved several mechanisms to combat host defense systems, and to avoid and modulate host immunity during infection, therefore benefitting their survival and replication. In the host, pathogens trigger responses from innate and adaptive immune systems that recognize and eliminate invaders. Two important innate defenses against pathogens are the programmed cell death pathways of apoptosis and autophagy. This Mini Review surveys the current knowledge of apoptosis and autophagy pathways in tick-pathogen interactions, as well as the strategies evolved by pathogens for their benefit. We then assess the limitations to studying both pathways and discuss their participation in the network of the tick immune system, before highlighting future perspectives in this field. The knowledge gained would significantly enhance our understanding of the defense responses in vector ticks that regulate pathogen infection and burden, and form the foundation for future research to identify novel approaches to the control of tick-borne diseases.
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Affiliation(s)
- Xin-Ru Wang
- *Correspondence: Xin-Ru Wang, ; Benjamin Cull,
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Hadji H, Bouchemal K. Effect of micro- and nanoparticle shape on biological processes. J Control Release 2021; 342:93-110. [PMID: 34973308 DOI: 10.1016/j.jconrel.2021.12.032] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/15/2022]
Abstract
In the drug delivery field, there is beyond doubt that the shape of micro- and nanoparticles (M&NPs) critically affects their biological fate. Herein, following an introduction describing recent technological advances for designing nonspherical M&NPs, we highlight the role of particle shape in cell capture, subcellular distribution, intracellular drug delivery, and cytotoxicity. Then, we discuss theoretical approaches for understanding the effect of particle shape on internalization by the cell membrane. Subsequently, recent advances on shape-dependent behaviors of M&NPs in the systemic circulation are detailed. In particular, the interaction of M&NPs with blood proteins, biodistribution, and circulation under flow conditions are analyzed. Finally, the hurdles and future directions for developing nonspherical M&NPs are underscored.
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Affiliation(s)
- Hicheme Hadji
- Université Paris-Saclay, Institut Galien Paris Saclay, CNRS UMR 8612, 92296 Châtenay-Malabry, France
| | - Kawthar Bouchemal
- Université Paris-Saclay, Institut Galien Paris Saclay, CNRS UMR 8612, 92296 Châtenay-Malabry, France.
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Gährs M, Schrenk D. Suppression of apoptotic signaling in rat hepatocytes by non-dioxin-like polychlorinated biphenyls depends on the receptors CAR and PXR. Toxicology 2021; 464:153023. [PMID: 34743025 DOI: 10.1016/j.tox.2021.153023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 10/19/2021] [Accepted: 11/02/2021] [Indexed: 10/19/2022]
Abstract
Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) represent a sub-group of persistent organic pollutants found in food, environmental samples and human and animal tissues. Promotion of pre-neoplastic lesions in rodent liver has been suggested as an indicator for a possible increased risk of liver cancer in humans exposed to NDL-PCBs. In rodent hepatocytes, suppression of DNA damage-triggered apoptosis is a typical mode of action of liver tumor promoters. Here, we report that NDL-PCBs suppress apoptosis in rat hepatocytes treated in culture with an apoptogenic dose of UV light. Suppression became less pronounced when the constitutive androstane receptor (CAR) and/or the pregnane-X-receptor (PXR) where knocked-out using siRNAs, while knocking-out both receptors led to a full reconstitution of apoptosis. In contrast, suppression of apoptosis by the CAR or PXR activators phenobarbital or dexamethasone were CAR- or PXR-specific. Induction and suppression of apoptosis were paralleled by changes in caspase 3/7, 8 and 9 activities. Our findings indicate that NDL-PCBs can suppress UV-induced apoptosis in rat hepatocytes by activating CAR and PXR. It needs further investigation if these mechanisms of action are also of relevance for human liver.
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Affiliation(s)
- Maike Gährs
- Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany
| | - Dieter Schrenk
- Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
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35
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Hosseinzadeh S, Nazari H, Esmaeili E, Hatamie S. Polyethylene glycol triggers the anti-cancer impact of curcumin nanoparticles in sw-1736 thyroid cancer cells. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:112. [PMID: 34453618 PMCID: PMC8403115 DOI: 10.1007/s10856-021-06593-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 07/31/2021] [Indexed: 06/13/2023]
Abstract
Curcumin has been recognized as an effective anticancer agent. However, due to its hydrophobic property, the cell absorption is not satisfied. Herein, the curcumin nanoparticles were prepared in the presence of polyethylene glycol 6000 (PEG6000) to reduce its elimination by immune system. For first time, not only the curcumin was encapsulated within the niosome nanoparticles modified by PEG, there are no reports related to the anticancer property of curcumin against thyroid cancers. The nanoparticles was developed and its anticancer was studied on sw-1736 cancer cell line. The nanoparticles were examined by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Also, the release profile of curcumin, the IC50 concentration, the radical amount and the gene expression were evaluated. The optimized nanoparticles showed a diameter of 212 ± 31 nm by SEM and the encapsulation efficiency and loading capacity of 76% and 16.8% respectively. DLS confirmed the polydispersity index (PDI) of 0.596 and the release model was shown a sustained release with the delivery of 68% curcumin after 6 days. Also, the nanoparticles indicated the higher storage stability at 4 °C. After the cell treatment, the apoptotic bodies were appeared and IC50 was obtained as 0.159 mM. Moreover, the generated radicals by the treated cells was 86% after 72 h and the gene pattern indicated the bax/bcl2 ratio of 6.83 confirming the apoptosis effect of the nanoparticles. The results approved the nanoparticles could be suggested as an anticancer drug candidate for thyroid cancers. The encapsulated curcumin within the niosome nanoparticles modified with PEG, could be released and up-taken by the thyroid cancer cell line due to the same hydrophobic property of cell membrane and the niosome particles. The reaction between curcumin and cellular components generates radicals and activates the apoptotic pathway. The corresponding reaction finally makes cell death.
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Affiliation(s)
- Simzar Hosseinzadeh
- Medical nanotechnology and tissue engineering research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Tissue engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hojjatollah Nazari
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Shadie Hatamie
- Institute of NanoEngineering and MicroSystems National Tsing Hua University Hsinchu, 30013, Hsinchu, Taiwan, ROC
- Department of Power Mechanical Engineering National Tsing Hua University Hsinchu, 30013, Hsinchu, Taiwan, ROC
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Mitochondrion-Dependent Apoptosis Is Essential for Rickettsia parkeri Infection and Replication in Vector Cells. mSystems 2021; 6:6/2/e01209-20. [PMID: 33727398 PMCID: PMC8546998 DOI: 10.1128/msystems.01209-20] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Apoptosis is an innate immune response induced by infection in eukaryotes that contributes significantly to protection from pathogens. However, little is known about the role of apoptosis in the interactions of arthropod vectors with the rickettsiae that they transmit. Rickettsia spp. are vector-borne obligately intracellular bacteria and display different degrees of virulence in their eukaryotic hosts. In this study, we found that infection with Rickettsia parkeri (Rp) activated the apoptosis pathway in an Amblyomma americanum tick cell line (AAE2), as evidenced by the loss of phospholipid membrane asymmetry and DNA fragmentations. Additionally, infection with Rp also led to apoptosis activation in cell lines of different tick species. Interestingly, suppressing apoptosis decreased Rp infection and replication, while the activation of apoptosis increased Rp accumulation at the early stage of infection. Moreover, mitochondrion-dependent apoptosis was essential for Rp infection and replication in vector cells, and apoptosis induction required intracellular rickettsia replication. We further showed that Rp utilizes two different survival strategies to modulate apoptosis in the arthropod vectors and mammalian host cells. There was no direct correlation between apoptosis activation in vector cells and rickettsial pathogenicity. These novel findings indicate a possible mechanism whereby apoptosis facilitates infection and replication of a Rickettsia sp. in an arthropod vector. These results contribute to our understanding of how the vector's responses to pathogen infection affect pathogen replication and therefore transmission. IMPORTANCE Rickettsioses, infections caused by the genus Rickettsia, are among the oldest known infectious diseases. Ticks are essential arthropod vectors for rickettsiae, and knowledge about the interactions between ticks, their hosts, and pathogens is fundamental for identifying drivers of tick-borne rickettsioses. Despite the rapid development in apoptosis research with rickettsiae, little is known regarding the role of apoptosis in the interactions between Rickettsia spp., vertebrate hosts, and arthropod vectors. Here, we demonstrated that mitochondrion-dependent apoptosis is essential for rickettsial infection and replication in vector cells and that apoptosis induction requires intracellular rickettsial replication. However, rickettsial pathogenicity is not linked with apoptosis activation in tick cells. Our findings improve understanding of the apoptosis mechanism in arthropods exploited by rickettsiae and also the potential to discover specific targets for new vaccines and drugs to prevent or treat rickettsial infections.
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van Berkel AA, Santos TC, Shaweis H, van Weering JRT, Toonen RF, Verhage M. Loss of MUNC18-1 leads to retrograde transport defects in neurons. J Neurochem 2020; 157:450-466. [PMID: 33259669 PMCID: PMC8247427 DOI: 10.1111/jnc.15256] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/24/2020] [Accepted: 11/26/2020] [Indexed: 12/11/2022]
Abstract
Loss of the exocytic Sec1/MUNC18 protein MUNC18-1 or its target-SNARE partners SNAP25 and syntaxin-1 results in rapid, cell-autonomous and unexplained neurodegeneration, which is independent of their known role in synaptic vesicle exocytosis. cis-Golgi abnormalities are the earliest cellular phenotypes before degeneration occurs. Here, we investigated whether loss of MUNC18-1 causes defects in intracellular membrane transport pathways in primary murine neurons that may explain neurodegeneration. Electron, confocal and super resolution microscopy confirmed that loss of MUNC18-1 expression results in a smaller cis-Golgi. In addition, we now show that medial-Golgi and the trans-Golgi Network are also affected. However, stacking and cisternae ultrastructure of the Golgi were normal. Overall, ultrastructure of null mutant neurons was remarkably normal just hours before cell death occurred. By synchronizing protein trafficking by conditional cargo retention in the endoplasmic reticulum using selective hooks (RUSH) and immunocytochemistry, we show that anterograde Endoplasmic Reticulum-to-Golgi and Golgi exit of endogenous and exogenous proteins were normal. In contrast, loss of MUNC18-1 caused reduced retrograde Cholera Toxin B-subunit transport from the plasma membrane to the Golgi. In addition, MUNC18-1-deficiency resulted in abnormalities in retrograde TrkB trafficking in an antibody uptake assay. We conclude that MUNC18-1 deficient neurons have normal anterograde but reduced retrograde transport to the Golgi. The impairments in retrograde pathways suggest a role of MUNC18-1 in endosomal SNARE-dependent fusion and provide a plausible explanation for the observed Golgi abnormalities and cell death in MUNC18-1 deficient neurons.
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Affiliation(s)
- Annemiek A van Berkel
- Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), University Medical Center Amsterdam, Amsterdam, The Netherlands.,Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands
| | - Tatiana C Santos
- Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands
| | - Hesho Shaweis
- Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands
| | - Jan R T van Weering
- Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Ruud F Toonen
- Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands
| | - Matthijs Verhage
- Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), University Medical Center Amsterdam, Amsterdam, The Netherlands.,Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands
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Jackson K, Devaraj E, Lakshmi T, Rajeshkumar S, Dua K, Chellappan DK, Raghunandhakumar S. Cytotoxic potentials of silibinin assisted silver nanoparticles on human colorectal HT-29 cancer cells. Bioinformation 2020; 16:817-827. [PMID: 34803254 PMCID: PMC8573457 DOI: 10.6026/97320630016817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 09/26/2020] [Accepted: 09/26/2020] [Indexed: 12/16/2022] Open
Abstract
It is of interest to study the cytotoxicity of silibinin assisted silver nanoparticles in human colorectal (HT-29) cancer cells. Silver nanoparticles were synthesized using silibinin as a reducing agent. The synthesized silibinin assisted silver nanoparticles ( SSNPs) were characterized and analyzed using a transmission electron microscope and spectrophotometer. The SSNPs synthesized in this study are spherical and their size ranges from 10 to 80 nm. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/mL) of SSNPs and cytotoxicity was evaluated. The apoptosis was using flow cytometry. p53 protein expression using western blot. SSNPs are induced a decrease in viability and increased concentration-dependent cytotoxicity in HT-29 cells. SSNPs treatment also caused apoptosis-related morphological changes. SSNPs treatments at 8 and 16 ng/ml showed a prominent apoptotic change i.e., 70.3% and 83.6% respectively, and decreased viability of HT-29 cells 20% and 11.2% respectively as compared to control cells. SSNPs treatments induced p53 expression in HT-29 cells. Data shows that SSNPs have the potential to induce apoptosis in colorectal cancer cells. This provides insights for the further evaluation of SSNPs in fighting colon cancer.
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Affiliation(s)
- Kiren Jackson
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India 600 077
| | - Ezhilarasan Devaraj
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India 600 077
| | - Thangavelu Lakshmi
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India 600 077
| | - Shanmugam Rajeshkumar
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India 600 077
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
| | - Subramanian Raghunandhakumar
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India 600 077
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Dutta D, Palmer XL, Ortega-Rodas J, Balraj V, Dastider IG, Chandra S. Biomechanical and Biophysical Properties of Breast Cancer Cells Under Varying Glycemic Regimens. Breast Cancer (Auckl) 2020; 14:1178223420972362. [PMID: 33239879 PMCID: PMC7672722 DOI: 10.1177/1178223420972362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 10/12/2020] [Indexed: 01/27/2023] Open
Abstract
Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, MDA-MB-231), and human normal mammary epithelial cells (MCF-10A), under different levels of glycemic stress. These were used to study both benign and malignant breast tissue behaviors. Benign cells (MCF-10A) recorded higher Young's modulus values than malignant cells (MCF-7 and MDA-231) under normoglycemic conditions, which agrees with the current literature. Moreover, exposure to high glucose (for 48 hours) decreased Young's modulus in both benign and malignant cells, to the effect that the cancer cells showed a complete loss in elasticity with high glucose. This provides a possible insight into a link between glycemic stress and cytoskeletal strength. This work suggests that reducing glycemic stress in cancer patients and those at risk can prove beneficial in restoring normal cytoskeletal structure.
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Affiliation(s)
- Diganta Dutta
- Department of Physics and Astronomy, University of Nebraska at Kearney, Kearney, NE, USA
| | - Xavier-Lewis Palmer
- Department of Biomedical Engineering, Old Dominion University, Norfolk, VA, USA
| | - Jose Ortega-Rodas
- Department of Biology, University of Nebraska at Kearney, Kearney, NE, USA
| | | | | | - Surabhi Chandra
- Department of Biology, University of Nebraska at Kearney, Kearney, NE, USA
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Liu G, Xu X, Jiang L, Ji H, Zhu F, Jin B, Han J, Dong X, Yang F, Li B. Targeted Antitumor Mechanism of C-PC/CMC-CD55sp Nanospheres in HeLa Cervical Cancer Cells. Front Pharmacol 2020; 11:906. [PMID: 32636744 PMCID: PMC7319041 DOI: 10.3389/fphar.2020.00906] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/03/2020] [Indexed: 12/20/2022] Open
Abstract
In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-β, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.
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Affiliation(s)
- Guoxiang Liu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xiaohui Xu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Liangqian Jiang
- Department of Medical Genetics, Linyi People's Hospital, Linyi, China
| | - Huanhuan Ji
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Feng Zhu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Bingnan Jin
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Jingjing Han
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xiaolei Dong
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Fanghao Yang
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Bing Li
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China.,Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Martínez MA, Lopez-Torres B, Rodríguez JL, Martínez M, Maximiliano JE, Martínez-Larrañaga MR, Anadón A, Ares I. Toxicologic evidence of developmental neurotoxicity of Type II pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells. Food Chem Toxicol 2020; 137:111173. [PMID: 32028016 DOI: 10.1016/j.fct.2020.111173] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 01/28/2020] [Accepted: 01/29/2020] [Indexed: 11/28/2022]
Abstract
We attempted to identify cellular mechanisms as an approach to screen chemicals for the potential to cause developmental neurotoxicity. We examine, in SH-SY5Y cells, whether apoptosis and oxidative stress via reactive oxygen species (ROS) generation, caspase 3/7 activation, gene expression (Bax, Bcl-2, Casp-3, BNIP3, p53 and Nrf2) alterations and necrosis by release of cytosolic adenylate kinase (AK), underlie direct effects of the pyrethroids cyfluthrin and alpha-cypermethrin. We also determined transcriptional alterations of genes (TUBB3, NEFL, NEFH, GAP43, CAMK2A, CAMK2B, WNT3A, WNT5A, WNT7A, SYN1 and PIK3C3) linked to neuronal development and maturation. Our results indicate that cyfluthrin and alpha-cypermethrin have the ability to elicit concentration-dependent increases in AK release, cellular ROS production, caspase 3/7 activity and gene expression of apoptosis and oxidative stress mediators. Both pyrethroids caused changes in mRNA expression of key target genes linked to neuronal development. These changes might reflect in a subsequent neuronal dysfunction. Our study shows that SH-SY5Y cell line is a valuable in vitro model for predicting development neurotoxicity. Our research provides evidence that cyfluthrin and alpha-cypermethrin have the potential to act as developmental neurotoxic compounds. Additional information is needed to improve the utility of this in vitro model and/or better understand its predictive capability.
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Affiliation(s)
- María-Aránzazu Martínez
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
| | - Bernardo Lopez-Torres
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
| | - José-Luis Rodríguez
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
| | - Marta Martínez
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain.
| | - Jorge-Enrique Maximiliano
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
| | - María-Rosa Martínez-Larrañaga
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
| | - Arturo Anadón
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain.
| | - Irma Ares
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain
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Carneiro LS, Martínez LC, Gonçalves WG, Santana LM, Serrão JE. The fungicide iprodione affects midgut cells of non-target honey bee Apis mellifera workers. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 189:109991. [PMID: 31780208 DOI: 10.1016/j.ecoenv.2019.109991] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 11/07/2019] [Accepted: 11/20/2019] [Indexed: 06/10/2023]
Abstract
The honey bee Apis mellifera is an important pollinator of agricultural crops and natural forests. Honey bee populations have declined over the years, as a result of diseases, pesticides, and management problems. Fungicides are the main pesticides found in pollen grains, which are the major source of protein for bees. The objective of this study was to evaluate the cytotoxic effects of the fungicide iprodione on midgut cells of adult A. mellifera workers. Bees were fed on iprodione (LD50, determined by the manufacturer) for 12 or 24 h, and the midgut was examined using light and transmission electron microscopies. The expression level of the autophagy gene atg1 was assessed in midgut digestive cells. Cells of treated bees had signs of apoptosis: cytoplasmic vacuolization, apical cell protrusions, nuclear fragmentation, and chromatin condensation. Ultrastructural analysis revealed some cells undergoing autophagy and necrosis. Expression of atg1 was similar between treated and control bees, which can be explained by the facts that digestive cells had autolysosomes, whereas ATG-1 is found in the initial phases of autophagy. Iprodione acts by inhibiting the synthesis of glutathione, leading to the generation of reactive oxygen species, which in turn can induce different types of cell death. The results indicate that iprodione must be used with caution because it has side effects on non-target organisms, such as pollinator bees.
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Affiliation(s)
- Lenise Silva Carneiro
- Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Luis Carlos Martínez
- Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Wagner Gonzaga Gonçalves
- Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Luanda Medeiros Santana
- Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - José Eduardo Serrão
- Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil.
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Laghezza Masci V, Ovidi E, Taddei AR, Turchetti G, Tiezzi A, Giacomello P, Garzoli S. Apoptotic Effects on HL60 Human Leukaemia Cells Induced by Lavandin Essential Oil Treatment. Molecules 2020; 25:E538. [PMID: 31991893 PMCID: PMC7036901 DOI: 10.3390/molecules25030538] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/17/2020] [Accepted: 01/23/2020] [Indexed: 12/20/2022] Open
Abstract
Recent scientific investigations have reported a number of essential oils to interfere with intracellular signalling pathways and to induce apoptosis in different cancer cell types. In this paper, Lavandin Essential Oil (LEO), a natural sterile hybrid obtained by cross-breeding L. angustifolia × L. latifolia, was tested on human leukaemia cells (HL60). Based on the MTT results, the reduced cell viability of HL60 cells was further investigated to determine whether cell death was related to the apoptotic process. HL60 cells treated for 24 h with LEO were processed by flow cytometry, and the presence of Annexin V was measured. The activation of caspases-3 was evaluated by western blot and immunofluorescence techniques. Treated cells were also examined by scanning and transmission electron microscopy to establish the possible occurrence of morphological alterations during the apoptotic process. LEO main compounds, such as linalool, linalyl acetate, 1,8-cineole, and terpinen-4-ol, were also investigated by MTT and flow cytometry analysis. The set of obtained results showed that LEO treatments induced apoptosis in a dose-dependent, but not time-dependent, manner on HL60 cells, while among LEO main compounds, both terpinen-4-ol and linalyl acetate were able to induce apoptosis.
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Affiliation(s)
- Valentina Laghezza Masci
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy; (V.L.M.); (E.O.); (G.T.); (A.T.)
| | - Elisa Ovidi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy; (V.L.M.); (E.O.); (G.T.); (A.T.)
| | | | - Giovanni Turchetti
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy; (V.L.M.); (E.O.); (G.T.); (A.T.)
| | - Antonio Tiezzi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy; (V.L.M.); (E.O.); (G.T.); (A.T.)
| | - Pierluigi Giacomello
- Department of Drug Chemistry and Technology, Sapienza University, 00185 Rome, Italy;
| | - Stefania Garzoli
- Department of Drug Chemistry and Technology, Sapienza University, 00185 Rome, Italy;
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Musso F, Pronsato L, Milanesi L, Vasconsuelo A, Faraoni MB. Non-polar extracts of Nicotiana glauca (Solanaceae) induce apoptosis in human rhabdomyosarcoma cells. RODRIGUÉSIA 2020. [DOI: 10.1590/2175-7860202071047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue tumour in children and adolescents. It originates in normal skeletal muscle from myogenic cells that have failed to fully differentiate, and it usually has a poor prognosis. Current RMS therapy has many adverse effects. Hence, new treatments are needed. Various pharmacological properties, such as analgesic, antineoplastic, antimicrobial, and antiparasitic properties, have been demonstrated in species of the Solanaceae family. We performed ethanolic extraction from leaves of Nicotiana glauca (Solanaceae), and the extract was successively partitioned with n-hexane, chloroform, and ethyl acetate. We evaluated the effects of extracts on RMS cells, and we found that the extracts trigger apoptosis. By bio-guided fractionation assays, we identified the apoptotic agents. Morphological assessment after apoptotic cell induction of cultured cells, mitochondrial and nuclear morphology by Mitotracker, and 4,6-diamidino-2-phenylindole (DAPI) staining, respectively, were analysed in fluorescent microscopy. The capacity of the cells to migrate or proliferate was analysed by the Petit assay, followed by methylene blue staining. NMR and GC-MS spectrometry were used to identify palmitic acid and scopoletin as the phytochemicals responsible for the observed effects. These results indicate that these compounds are apoptotic inducers and they could be useful as chemotherapeutic agents against muscle tumours.
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45
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Tovar MA, Parkhurst A, Matuczinski E, Balenger S, Giancarlo LC. Synthesis of a superparamagnetic iron oxide based nano-complex for targeted cell death of glioblastoma cells. NANOTECHNOLOGY 2019; 30:465101. [PMID: 31323657 DOI: 10.1088/1361-6528/ab33d4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
In the last ten years, there has been little advancement in the treatment of the aggressive brain cancer Glioblastoma Multiforme (GBM). This research describes the synthesis of a superparamagnetic iron oxide (SPION)-based nanotheraputic complex for use in targeting and killing aggressive mesenchymal GBM cells. The average sizes and magnetic properties of the synthesized SPIONs are tailored via a novel time-controlled approach to a previously described electrochemical reaction. Through this synthetic method, the optimal particle size where maximal thermal energy is released upon stimulation with an external magnetic field was determined to be 21 nm. The nano-complex was further modified to selectively target GBM cells by adding a heterobifunctional poly(ethylene) glycol polymer crosslinked to TWEAK (a GBM targeting peptide). Preliminary investigation with FITC Annexin V/propidium iodide fluorescent probes and transmission electron microscopy revealed biochemical and morphological evidence of both SPION internalization and cytotoxic effects over the course of three hours. Thus, these nano-complexes hold promise as a potential treatment agent for an otherwise untreatable disease.
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Affiliation(s)
- Matthew A Tovar
- Department of Chemistry, University of Mary Washington, Fredericksburg, VA, United States of America
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46
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Zhang Q, Chen W, Lv X, Weng Q, Chen M, Cui R, Liang G, Ji J. Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress. Front Pharmacol 2019; 10:1180. [PMID: 31680962 PMCID: PMC6802400 DOI: 10.3389/fphar.2019.01180] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 09/13/2019] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related deaths globally. Despite advances in diagnosis and treatment, the incidence and mortality of HCC continue to rise. Piperlongumine (PL), an alkaloid isolated from the fruit of the long pepper, is known to selectively kill tumor tissues while sparing their normal counterparts. However, the killing effects of PL on HCC and the underlying mechanism of PL are not clear. We report that PL may interact with thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, and induce reactive oxygen species (ROS)-mediated apoptosis in HCC cells. Our results suggest that PL induces a lethal endoplasmic reticulum (ER) stress response in HCC cells by targeting TrxR1 and increasing intracellular ROS levels. Notably, PL treatment reduces TrxR1 activity and tumor cell burden in vivo. Additionally, TrxR1 is significantly upregulated in existing HCC databases and available HCC clinical specimens. Taken together, these results suggest PL as a novel anticancer candidate for the treatment of HCC. More importantly, this study reveals that TrxR1 might be an effective target in treating HCC.
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Affiliation(s)
- Qianqian Zhang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Weiqian Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Xiuling Lv
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Qiaoyou Weng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Ri Cui
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Guang Liang
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
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47
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Donmez HG, Beksac MS. Comparison of cytological and immunocytochemical methods for detecting apoptotic epithelial cells in cervicovaginal smears. Diagn Cytopathol 2019; 47:1277-1282. [PMID: 31576675 DOI: 10.1002/dc.24316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/28/2019] [Accepted: 09/06/2019] [Indexed: 11/08/2022]
Abstract
BACKGROUND Several methods have been applied to detect death cells in tissue, cell culture, and fluid samples. We aimed to compare the cytological and immunocytochemical methods for detecting apoptotic cells in cervicovaginal smears. METHODS Cervicovaginal smears were taken from 102 women for various gynecological complaints. The slides were stained using the Papanicolaou (Pap)-staining method for cytological evaluation. Cleaved caspase 3 (CC3) antibody was used to detect apoptosis by immunocytochemically, and H-Score was used for the evaluation. In Pap-stained smears, apoptosis was detected and evaluated using our new scoring system by the examination of morphological changes of epithelial cells such as apoptotic bodies, blebbing, karyopyknosis, karyorrhexis, and karyolysis. We used Kappa analysis to understand whether there is an agreement between cytological and immunocytochemical methods for detecting apoptotic cells. RESULTS Cytological and immunocytochemical methods showed similarities at a moderate level (κ = 0.482, P < .001). The cytological and immunocytochemical scores were also similar to each other at a fair level (κ = 0.373, P < .001). Pap smears had a sensitivity of 64.40% (95% CI: 50.12-76.01), specificity of 86.04% (95% CI: 72.65-94.83), positive likelihood ratio of 4.62, negative likelihood ratio of 0.41, positive predictive value of 86.36%, negative predictive value of 63.79%, and overall probability of 73.53% compared to immunocytochemical staining. CONCLUSIONS Our results demonstrate that Pap smear and cytological scores alone were not good enough to identify apoptosis compared to the immunocytochemical studies. However, because of its high specificity, it may still be an adequate method to detect apoptotic cells.
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Affiliation(s)
- Hanife Guler Donmez
- Department of Biology, Faculty of Science, Hacettepe University, Ankara, Turkey
| | - Mehmet Sinan Beksac
- Department of Gynecology and Obstetrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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48
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Mishra PK, Adameova A, Hill JA, Baines CP, Kang PM, Downey JM, Narula J, Takahashi M, Abbate A, Piristine HC, Kar S, Su S, Higa JK, Kawasaki NK, Matsui T. Guidelines for evaluating myocardial cell death. Am J Physiol Heart Circ Physiol 2019; 317:H891-H922. [PMID: 31418596 DOI: 10.1152/ajpheart.00259.2019] [Citation(s) in RCA: 167] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cell death is a fundamental process in cardiac pathologies. Recent studies have revealed multiple forms of cell death, and several of them have been demonstrated to underlie adverse cardiac remodeling and heart failure. With the expansion in the area of myocardial cell death and increasing concerns over rigor and reproducibility, it is important and timely to set a guideline for the best practices of evaluating myocardial cell death. There are six major forms of regulated cell death observed in cardiac pathologies, namely apoptosis, necroptosis, mitochondrial-mediated necrosis, pyroptosis, ferroptosis, and autophagic cell death. In this article, we describe the best methods to identify, measure, and evaluate these modes of myocardial cell death. In addition, we discuss the limitations of currently practiced myocardial cell death mechanisms.
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Affiliation(s)
- Paras K Mishra
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Adriana Adameova
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University of Bratislava, Bratislava, Slovakia
| | - Joseph A Hill
- Departments of Medicine (Cardiology) and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Christopher P Baines
- Department of Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri
| | - Peter M Kang
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - James M Downey
- Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, Alabama
| | - Jagat Narula
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Masafumi Takahashi
- Division of Inflammation Research, Center of Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Antonio Abbate
- Virginia Commonwealth University, Pauley Heart Center, Richmond, Virginia
| | - Hande C Piristine
- Department of Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, Texas
| | - Sumit Kar
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Shi Su
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Jason K Higa
- Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii
| | - Nicholas K Kawasaki
- Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii
| | - Takashi Matsui
- Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii
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49
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Medina Cruz D, Tien-Street W, Zhang B, Huang X, Vernet Crua A, Nieto-Argüello A, Cholula-Díaz JL, Martínez L, Huttel Y, Ujué González M, García-Martín JM, Webster TJ. Citric Juice-mediated Synthesis of Tellurium Nanoparticles with Antimicrobial and Anticancer Properties. GREEN CHEMISTRY : AN INTERNATIONAL JOURNAL AND GREEN CHEMISTRY RESOURCE : GC 2019; 21:1982-1988. [PMID: 31156349 PMCID: PMC6542685 DOI: 10.1039/c9gc00131j] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Bacterial infections and cancer are two of the most significant concerns that the current healthcare system should tackle nowadays. Green nanotechnology is presented as a feasible solution that is able to produce materials with significant anticancer and antibacterial activity, while overcoming the main limitations of traditional synthesis. In the present work, orange, lemon and lime extracts were used as both reducing and capping agents for the green synthesis of tellurium nanoparticles (TeNPs) using a microwave-assisted reaction. TeNPs showed a uniform size distribution, and rod- and cubic-shapes, and were extensively characterized in terms of morphology, structure and composition using TEM, SEM, XPS, XRD, FTIR and EDX analysis. TeNPs showed an important antibacterial activity against both Gram-negative and -positive bacteria in a range concentrations from 5 to 50 μg/mL over a 24-hour time period. Besides, nanoparticles showed anticancer effect towards human melanoma cells over 48 hours at concentrations up to 50 μg/mL. Moreover, the Te nanostructures showed no significant cytotoxic effect towards human dermal fibroblast at concentrations up to 50 μg/mL. Therefore, we present an environmentally-friendly and cost-effective synthesis of TeNPs using only fruit juices and showing enhanced and desirable biomedical properties towards both infectious diseases and cancer.
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Affiliation(s)
- David Medina Cruz
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - William Tien-Street
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| | - Bohan Zhang
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - Xinjing Huang
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - Ada Vernet Crua
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - Alfonso Nieto-Argüello
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501, Monterrey, NL 64849, Mexico
| | - Jorge L. Cholula-Díaz
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501, Monterrey, NL 64849, Mexico
| | - Lidia Martínez
- Materials Science Factory. Instituto de Ciencia de Materiales de Madrid, ICMM-CSIC, Sor Juana Inés de la Cruz 3, 28049 Madrid, Spain
| | - Yves Huttel
- Materials Science Factory. Instituto de Ciencia de Materiales de Madrid, ICMM-CSIC, Sor Juana Inés de la Cruz 3, 28049 Madrid, Spain
| | - María Ujué González
- Instituto de Micro y Nanotecnología, IMN-CNM, CSIC (CEI UAM+CSIC), Isaac Newton 8, 28760 Tres Cantos, Spain
| | - José Miguel García-Martín
- Instituto de Micro y Nanotecnología, IMN-CNM, CSIC (CEI UAM+CSIC), Isaac Newton 8, 28760 Tres Cantos, Spain
| | - Thomas J. Webster
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
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50
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Vernet Crua A, Medina D, Zhang B, González MU, Huttel Y, García-Martín JM, Cholula-Díaz JL, Webster TJ. Comparison of cytocompatibility and anticancer properties of traditional and green chemistry-synthesized tellurium nanowires. Int J Nanomedicine 2019; 14:3155-3176. [PMID: 31118629 PMCID: PMC6501707 DOI: 10.2147/ijn.s175640] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Traditional physicochemical approaches for the synthesis of compounds, drugs, and nanostructures developed as potential solutions for antimicrobial resistance or against cancer treatment are, for the most part, facile and straightforward. Nevertheless, these approaches have several limitations, such as the use of toxic chemicals and production of toxic by-products with limited biocompatibility. Therefore, new methods are needed to address these limitations, and green chemistry offers a suitable and novel answer, with the safe and environmentally friendly design, manufacturing, and use of minimally toxic chemicals. Green chemistry approaches are especially useful for the generation of metallic nanoparticles or nanometric structures that can effectively and efficiently address health care concerns. Objective Here, tellurium (Te) nanowires were synthesized using a novel green chemistry approach, and their structures and cytocompatibility were evaluated. Method An easy and straightforward hydrothermal method was employed, and the Te nanowires were characterized using transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and optical microscopy for morphology, size, and chemistry. Cytotoxicity tests were performed with human dermal fibroblasts and human melanoma cells (to assess anticancer properties). The results showed that a treatment with Te nanowires at concentrations between 5 and 100 μg/mL improved the proliferation of healthy cells and decreased cancerous cell growth over a 5-day period. Most importantly, the green chemistry -synthesized Te nanowires outperformed those produced by traditional synthetic chemical methods. Conclusion This study suggests that green chemistry approaches for producing Te nanostructures may not only reduce adverse environmental effects resulting from traditional synthetic chemistry methods, but also be more effective in numerous health care applications.
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Affiliation(s)
- Ada Vernet Crua
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA, .,Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA, .,Universitat Rovira I Virgili, Tarragona, Spain
| | - David Medina
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA, .,Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA,
| | - Bohan Zhang
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA, .,Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA,
| | - María Ujué González
- Instituto de Micro y Nanotechnologia, IMN-CNM, CSIC (CEI UAM+CSIC), Tres Cantos, Spain
| | - Yves Huttel
- Materials Science Factory, Instituto de Ciencias de Materiales, ICMN-CSIC, Madrid, Spain
| | | | - Jorge L Cholula-Díaz
- School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, NL, Mexico
| | - Thomas J Webster
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA, .,Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA,
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