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Nan A, Dumitrascu V, Flangea C, Dumitrescu G, Puscasiu D, Vlad T, Popescu R, Vlad C. From Chemical Composition to Antiproliferative Effects Through In Vitro Studies: Honey, an Ancient and Modern Hot Topic Remedy. Nutrients 2025; 17:1595. [PMID: 40362904 PMCID: PMC12074252 DOI: 10.3390/nu17091595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2025] [Revised: 04/30/2025] [Accepted: 05/05/2025] [Indexed: 05/15/2025] Open
Abstract
Honey is a natural product which has been used throughout time as a food, spice, and medicine. Its therapeutic use has its origins in direct empirical observations of various beneficial actions in terms of its anti-infectious, anti-inflammatory, and wound-healing effects, to which an antiproliferative effect is added. In the context of malignant transformation, reductions in chronic inflammation, antioxidant action, cell cycle arrest, and apoptosis activation contribute to this antiproliferative effect, achievements attributed mainly to the polyphenols in its composition. A multitude of in vitro studies performed on malignant cell cultures try to elucidate the real mechanism(s) that can scientifically explain this action. In addition, its use as an adjuvant in association with cytostatic therapy demonstrates a promising effect in enhancing its cytotoxic effect, but also in reducing some adverse effects. Highlighting these actions allows for further perspectives to be opened regarding the use of honey for therapeutic and also prophylactic purposes, as a food supplement. Future studies will support the identification of real antiproliferative effects in patients with malignant tumors in terms of actions on the human body as a whole, moving from cell cultures to complex implications.
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Affiliation(s)
- Alexandru Nan
- Doctoral School “Engineering of Vegetable and Animal Resources”, University of Life Sciences “King Mihai I” from Timişoara, Calea Aradului 119, 300645 Timisoara, Romania;
| | - Victor Dumitrascu
- Department of Biochemistry and Pharmacology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (V.D.); (C.V.)
| | - Corina Flangea
- Department of Biochemistry and Pharmacology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (V.D.); (C.V.)
| | - Gabi Dumitrescu
- Faculty of Bioengineering of Animal Resources, University of Life Sciences “King Mihai I” from Timisoara, Calea Aradului 119, 300645 Timisoara, Romania
- ANAPATMOL Research Center, “Victor Babes” University of Medicine and Pharmacy, E. Murgu 2, 300041 Timisoara, Romania; (D.P.); (T.V.); (R.P.)
| | - Daniela Puscasiu
- ANAPATMOL Research Center, “Victor Babes” University of Medicine and Pharmacy, E. Murgu 2, 300041 Timisoara, Romania; (D.P.); (T.V.); (R.P.)
- Department of Cell and Molecular Biology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Tania Vlad
- ANAPATMOL Research Center, “Victor Babes” University of Medicine and Pharmacy, E. Murgu 2, 300041 Timisoara, Romania; (D.P.); (T.V.); (R.P.)
- Department of Cell and Molecular Biology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Roxana Popescu
- ANAPATMOL Research Center, “Victor Babes” University of Medicine and Pharmacy, E. Murgu 2, 300041 Timisoara, Romania; (D.P.); (T.V.); (R.P.)
- Department of Cell and Molecular Biology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Cristian Vlad
- Department of Biochemistry and Pharmacology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (V.D.); (C.V.)
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Browne E, Kavanagh S, Devery S. The In Vitro Antioxidant and Immunomodulatory Effects of the Irish Monofloral Ivy and Heather Honey Varieties. Int J Mol Sci 2025; 26:3625. [PMID: 40332151 PMCID: PMC12027192 DOI: 10.3390/ijms26083625] [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: 03/18/2025] [Revised: 04/07/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
Honey has long been valued for its medicinal properties, yet the therapeutic potential of Irish monofloral honey remains largely unexplored. This study investigates the antioxidant and immunomodulatory effects of Irish ivy (Hedera helix) and heather (Calluna vulgaris) honey samples on PMA-differentiated THP-1 macrophages, a well-characterised immune model. Antioxidant capacity was assessed through free radical scavenging assays, DPPH and ORAC, while qPCR analysis examined the key inflammatory markers. Both the heather and ivy honey varieties demonstrated antioxidant activity, with heather honey exhibiting the highest total phenolic content (TPC), and ivy honey stimulating Nrf2 activation. Manuka honey showed the strongest radical scavenging capacity, as reflected in its higher ORAC and DPPH values. These findings suggest that the different honey varieties may exert antioxidant effects through distinct mechanisms. Exposure to honey reduced oxidative stress and upregulated the expression of a key antioxidant transcription regulator (Nrf2) and an associated downstream antioxidant defence enzyme, superoxide dismutase (SOD). Additionally, both the honey types exhibited immunomodulatory effects, upregulating pro-inflammatory cytokines, such as TNF-α and IL-1β, while increasing the expression of the anti-inflammatory cytokine IL-10. These findings suggest potential bioactive properties that warrant further investigation. Given the growing interest in alternative treatments for inflammation-related conditions, further research is warranted to determine whether the observed in vitro effects translate into clinically relevant outcomes. This study expands the current understanding of Irish monofloral honey, reinforcing its potential as a functional bioactive compound with relevance in antioxidant therapies, immune modulation, and wound healing.
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Affiliation(s)
- Emma Browne
- Bioscience Research Institute, Technological University of the Shannon, Athlone, Co., N37HD68 Westmeath, Ireland
| | - Siobhán Kavanagh
- Department of Pharmaceutical Sciences and Biotechnology, Technological University of the Shannon, Athlone, Co., N37HD68 Westmeath, Ireland
| | - Sinead Devery
- Department of Pharmaceutical Sciences and Biotechnology, Technological University of the Shannon, Athlone, Co., N37HD68 Westmeath, Ireland
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El-Sayed SE, Abdelaziz NA, El-Housseiny GS, Aboshanab KM. In vitro and preclinical evaluation of the antifungal activity of 6-methoxy-1 H-indole-2-carboxylic acid produced by Bacillus toyonensis strain OQ071612 formulated as nanosponge hydrogel. Microb Cell Fact 2025; 24:77. [PMID: 40169999 PMCID: PMC11959791 DOI: 10.1186/s12934-025-02688-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 03/04/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND In a previous study, 6-methoxy-1 H-indole-2-carboxylic acid (MICA) was isolated from the culture broth of Bacillus toyonensis strain OQ071612 soil isolate in our laboratory, and it demonstrated promising antifungal activities. The current study was designed to create a nanosponge (NS)-hydrogel (HG)-containing MICA followed by in vitro and preclinical evaluation for potential clinical use in the topical treatment of mycotic infections. RESULTS The enhanced NS formula was created using the Box Behnken Design (BBD), with independent process parameters including polyvinyl alcohol percentage (w/v%), homogenization time, speed and polymer: linker ratio. Dependent parameters were particle size (PS), polydispersity index (PDI), and entrapment efficiency percent (EE%). A hydrogel was formulated from the NS. In vitro drug release data indicated that the hydrogel best matched Higuchi's kinetic release model. The formulated NS-HG was stable and when compared to fluconazole, it exhibited increased antimycotic activity against C. albicans. An in vivo investigation revealed that MICA-NS-HG enhanced survival rates, wound gap repair, wound reduction, and inflammation inhibition. Masson's trichrome staining and histological analyses revealed increased collagen deposition and improved healing. Moreover, MICA hydrogel exhibited 1.5-fold greater permeability through rat skin compared to the control, 1% isoconazole. CONCLUSION The NS-HG formulation is a viable vehicle for better and more effective topical release of MICA. These findings represent a significant advancement in the formulation of MICA derived from naturally occurring soil bacteria.
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Affiliation(s)
- Sayed E El-Sayed
- Department of Microbiology and Immunology, Faculty of Pharmacy, Sixth of October City, Ahram Canadian University, 6 October city, Giza, 12451, Egypt
| | - Neveen A Abdelaziz
- Department of Microbiology and Immunology, Faculty of Pharmacy, Sixth of October City, Ahram Canadian University, 6 October city, Giza, 12451, Egypt
| | - Ghadir S El-Housseiny
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
| | - Khaled M Aboshanab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
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Balavigneswaran CK, Sundaram MK, Ramya V, Prakash Shyam K, Saravanakumar I, Kadalmani B, Ramkumar S, Selvaraj S, Thangavel P, Muthuvijayan V. Polysaccharide-Based Self-Healing Hydrogel for pH-Induced Smart Release of Lauric Acid to Accelerate Wound Healing. ACS APPLIED BIO MATERIALS 2025; 8:1343-1361. [PMID: 39903677 DOI: 10.1021/acsabm.4c01668] [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] [Indexed: 02/06/2025]
Abstract
It is highly desirable yet significantly challenging to fabricate an injectable, self-healing, controlled-release wound dressing that is responsive to the alkaline pH of the wounds. Herein, we propose a facile approach to prepare pH-responsive chitosan-oxidized carboxymethyl cellulose (CS-o-CMC) hydrogel constructs in which gelation was achieved via electrostatic and Schiff base formation. Importantly, the Schiff base was formed in acidic medium and the final pH of pregel solution was intrinsically raised to 7.0-7.4 due to the cross-linking by β-glycerol phosphate. The self-healing behavior of the hydrogel was an enthalpy-driven process and efficient in alkaline compared to acidic pH. The pH responsiveness offered a controlled release of lauric acid (LA) from CS-o-CMC/LA hydrogel and regulated the M2 polarization. Overall, reduction in inflammation led to rapid vascularization, reepithelialization, and significantly accelerated wound healing in rats. Our findings demonstrate a promising strategy for developing injectable, immunomodulatory wound dressings tailored to the challenging environment of wounds.
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Affiliation(s)
- Chelladurai Karthikeyan Balavigneswaran
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Manoj Kumar Sundaram
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Venkatesan Ramya
- Cancer Biology and Reproductive Endocrinology Laboratory, Department of Animal Science, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India
| | - Karuppiah Prakash Shyam
- Research and Development Division, V.V.D. and Sons Private Limited, Thoothukudi 628003, Tamil Nadu, India
| | - Iniyan Saravanakumar
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Balamuthu Kadalmani
- Cancer Biology and Reproductive Endocrinology Laboratory, Department of Animal Science, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India
| | - Sharanya Ramkumar
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Sowmya Selvaraj
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Ponrasu Thangavel
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
| | - Vignesh Muthuvijayan
- Tissue Engineering and Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
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Fan M, Zhu Y, Qian L, Hu C, Ding H. Association between preoperative inflammatory status via CALLY index and postoperative pneumonia occurrence in resectable esophageal squamous cell carcinoma patients: a retrospective cohort study. Front Oncol 2025; 15:1486983. [PMID: 40034601 PMCID: PMC11872739 DOI: 10.3389/fonc.2025.1486983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 01/29/2025] [Indexed: 03/05/2025] Open
Abstract
Background Postoperative pneumonia significantly affects recovery and prognosis in patients with esophageal squamous cell carcinoma. The CALLY index, derived from preoperative hematological parameters, may serve as a predictive marker for such complications. Objectives To assess the association between preoperative inflammatory status via the CALLY index and the occurrence of postoperative pneumonia in patients with resectable ESCC. Methods A retrospective cohort study was conducted from January 2020 to December 2022 at The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University. A total of 215 patients who met inclusion criteria were analyzed. Clinical data, including CALLY indices calculated preoperatively, were collected. Propensity score matching was applied to minimize confounding biases. The predictive value of the CALLY index was assessed using receiver operating characteristic analysis, and logistic regression was used to identify factors associated with postoperative pneumonia. Results ROC curve analysis demonstrated the CALLY index had an area under the curve of 0.764 for predicting postoperative pneumonia, with a cutoff value of 1.97 achieving 67.69% sensitivity and 84.67% specificity. In multivariate analysis, a lower CALLY index was significantly associated with increased pneumonia risk, independent of other factors (adjusted OR = 0.66, p < 0.001). High CALLY index scores correlated with a decreased likelihood of postoperative pneumonia, reinforcing its utility as a non-invasive prognostic marker. Conclusions The CALLY index is a robust, independent predictor of postoperative pneumonia in patients with resectable ESCC. Preoperative assessment of this index could enhance risk stratification and guide proactive management strategies to improve postoperative outcomes.
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Affiliation(s)
| | | | | | - Chuanxian Hu
- Department of Cardiothoracic Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
| | - Hui Ding
- Department of Cardiothoracic Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
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Li J, Liu H, Jia Y, Tuniyazi X, Liao X, Zhao J, Du Y, Fang Z, Lü G. SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice. Biochem Biophys Res Commun 2025; 749:151365. [PMID: 39855045 DOI: 10.1016/j.bbrc.2025.151365] [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: 12/25/2024] [Accepted: 01/19/2025] [Indexed: 01/27/2025]
Abstract
Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.
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Affiliation(s)
- Jing Li
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Hui Liu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Yutong Jia
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Xiayidanmu Tuniyazi
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Xia Liao
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Jinlong Zhao
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Yun Du
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Ziyi Fang
- College of Life Sciences and Technology, Xinjiang University, Urumqi, 830054, Xinjiang, China
| | - Guodong Lü
- College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
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Karami E, Parvizi MR, Izadi MR, Shirazi EJ. The Effect of Honey Supplementation on Skeletal Muscle-Related Inflammatory Markers Among Military Graduates After Overtraining. Health Sci Rep 2025; 8:e70428. [PMID: 39957976 PMCID: PMC11825975 DOI: 10.1002/hsr2.70428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 12/11/2024] [Accepted: 01/15/2025] [Indexed: 02/18/2025] Open
Abstract
Aims and Objectives Honey possesses specific anti-inflammatory properties. We evaluated the effects of oral honey supplementation on skeletal muscle-related inflammatory markers among military graduates after overtraining. Methods This randomized double-blind controlled trial was conducted on 42 overtrained military graduates who were randomly assigned to receive either honey supplementation (5 mL of 12% honey solution twice daily for 6 weeks) or a placebo for 6 weeks. In our study, we utilized Milk Vetch Sahand honey as the intervention. Serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), aldolase A, and creatine kinase (CK) were evaluated using the enzyme-linked immunosorbent assay method before and after the intervention. Results A total of 21 male participants with a mean age of 20.75 years were included in each group. No significant differences were found between the groups in the pre-intervention assessment of inflammatory biomarkers. However, in the post-intervention assessment, participants who received honey exhibited significantly smaller increases in CRP (p < 0.001), TNF-α (p = 0.001), aldolase A (p < 0.001), and CK levels (p < 0.001) compared to the controls. The mean changes in these biomarkers were notably lower in the honey group indicating a potential anti-inflammatory effect of honey. Conclusion This study demonstrates that honey supplementation significantly reduces inflammatory biomarkers such as TNF-α, CRP, aldolase A, and CK in military graduates experiencing overtraining, underscoring its potential to alleviate inflammation associated with intense physical training. To confirm and extend these findings, further research with larger sample sizes and longer follow-up periods is recommended.
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Affiliation(s)
- Esmail Karami
- Cognitive Neuroscience Research Center, AJA University of Medical SciencesTehranIran
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah, University of Medical SciencesTehranIran
| | | | - Mohammad Reza Izadi
- Department of Physical Education and Sports SciencesImam Hossein Comprehensive UniversityTehranIran
| | - Emad Jowhari Shirazi
- General Practitioner, Student Research CommitteeAJA University of Medical SciencesTehranIran
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Liu Z, Yoon CS, Lee H, Kim E, Yim JH, Kim TK, Oh H, Lee DS. The neuroprotective and anti-neuroinflammatory effects of ramalin synthetic derivatives in BV2 and HT22 cells. Biochem Pharmacol 2025; 231:116654. [PMID: 39581531 DOI: 10.1016/j.bcp.2024.116654] [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: 07/05/2024] [Revised: 11/19/2024] [Accepted: 11/21/2024] [Indexed: 11/26/2024]
Abstract
Ramalin, a strong antioxidant isolated from Antarctic lichens, has been shown to have potential therapeutic effects in the treatment of Alzheimer's disease. However, this compound is readily degraded in aqueous solutions, which restricts its development as a therapeutic agent. With a view toward addressing this problem, in this study, we modified the structure of ramalin to obtain more stable compounds and attempted to identify a derivative with the strongest neuroprotective properties. We synthesized a total of 20 ramalin derivatives, among which, RA-2 N was demonstrated to have the best neuroprotective effects, not only inhibiting inflammation in BV2 cells but also inhibiting inflammation-induced HT22 cell apoptosis in BV2-HT22 co-culture models. Moreover, we established that these effects were associated with an inhibition of the nuclear translocation of nuclear factor kappa-B (NF-κB). Our findings in this study revealed that the synthesis of ramalin derivatives is an effective approach for stabilizing this compound for therapeutic purposes. Given its modified structure, the RA-2 N derivative can inhibit inflammation and protect nerve cells, and thus indicate its potential application as a drug for treating neurodegenerative diseases.
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Affiliation(s)
- Zhiming Liu
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China.
| | - Chi-Su Yoon
- Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, South Korea.
| | - Hwan Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, South Korea.
| | - Eunae Kim
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, South Korea.
| | - Joung Han Yim
- Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, South Korea.
| | - Tai Kyoung Kim
- Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, South Korea.
| | - Hyuncheol Oh
- Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, South Korea.
| | - Dong-Sung Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, South Korea.
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El-Sayed SE, Abdelaziz NA, El-Housseiny GS, Aboshanab KM. Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis. Appl Microbiol Biotechnol 2024; 108:100. [PMID: 38217256 PMCID: PMC10786974 DOI: 10.1007/s00253-023-12819-3] [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: 08/04/2023] [Revised: 12/06/2023] [Accepted: 12/18/2023] [Indexed: 01/15/2024]
Abstract
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi's kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson's trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats' skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria. KEY POINTS: • Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized. • The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole. • Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.
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Affiliation(s)
- Sayed E El-Sayed
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Sixth of October City, Giza, 12451, Egypt
| | - Neveen A Abdelaziz
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Sixth of October City, Giza, 12451, Egypt
| | - Ghadir S El-Housseiny
- Department of Microbiology and Immunology, Faculty of Pharmacy, Organization of African Unity St, Ain Shams University, Abbassia, 11566, Cairo, Egypt
| | - Khaled M Aboshanab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Organization of African Unity St, Ain Shams University, Abbassia, 11566, Cairo, Egypt.
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Bangash AA, Alvi SS, Bangash MA, Ahsan H, Khan S, Shareef R, Villanueva G, Bansal D, Ahmad M, Kim DJ, Chauhan SC, Hafeez BB. Honey Targets Ribosome Biogenesis Components to Suppress the Growth of Human Pancreatic Cancer Cells. Cancers (Basel) 2024; 16:3431. [PMID: 39410048 PMCID: PMC11475701 DOI: 10.3390/cancers16193431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/02/2024] [Accepted: 10/08/2024] [Indexed: 10/20/2024] Open
Abstract
Pancreatic cancer (PanCa) is one of the deadliest cancers, with limited therapeutic response. Various molecular oncogenic events, including dysregulation of ribosome biogenesis, are linked to the induction, progression, and metastasis of PanCa. Thus, the discovery of new therapies suppressing these oncogenic events and ribosome biogenesis could be a novel therapeutic approach for the prevention and treatment of PanCa. The current study was designed to investigate the anti-cancer effect of honey against PanCa. Our results indicated that honey markedly inhibited the growth and invasive characteristics of pancreatic cancer cells by suppressing the mRNA expression and protein levels of key components of ribosome biogenesis, including RNA Pol-I subunits (RPA194 and RPA135) along with its transcriptional regulators, i.e., UBTF and c-Myc. Honey also induced nucleolar stress in PanCa cells by reducing the expression of various nucleolar proteins (NCL, FBL, and NPM). Honey-mediated regulation on ribosome biogenesis components and nucleolar organization-associated proteins significantly arrested the cell cycle in the G2M phase and induced apoptosis in PanCa cells. These results, for the first time, demonstrated that honey, being a natural remedy, has the potential to induce apoptosis and inhibit the growth and metastatic phenotypes of PanCa by targeting ribosome biogenesis.
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Affiliation(s)
- Aun Ali Bangash
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Sahir Sultan Alvi
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Muhammad Ali Bangash
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Haider Ahsan
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Shiza Khan
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Rida Shareef
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Georgina Villanueva
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Divyam Bansal
- Department of Kinesiology, Rice University, Houston, TX 77251, USA;
| | - Mudassier Ahmad
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Dae Joon Kim
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Subhash C. Chauhan
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Bilal Bin Hafeez
- South Texas Center of Excellence for Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; (A.A.B.); (M.A.B.); (H.A.); (S.K.); (R.S.); (G.V.); (M.A.); (D.J.K.); (S.C.C.)
- Department of Medicine and Oncology ISU, Division of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
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Dong L, Choi BR, Jeong HB, Lee H, Liu Z, Yoon D, Lee HE, Lee DS, Lee DY. Effects of Leaf Extracts from Genetic Resource of Capsicum spp. on Neuroprotection and Anti-Neuroinflammation in HT22 and in BV2 Cells. PLANTS (BASEL, SWITZERLAND) 2024; 13:2820. [PMID: 39409690 PMCID: PMC11478504 DOI: 10.3390/plants13192820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/05/2024] [Accepted: 10/07/2024] [Indexed: 10/20/2024]
Abstract
To develop functional varieties of Capsicum spp. leaves, 40 genetic resources were collected and extracted with 30% aqueous-fermented ethanol. We investigated the protective effects of extracts from 40 genetic resources of Capsicum spp. on glutamate-induced HT22 and LPS-induced BV2 cells. The results showed that the five extracts exhibited cell-protective activities. We also investigated the anti-inflammatory effects of these five extracts on LPS-induced BV2 cell neuroinflammation and found that 23OM18 exhibited superior anti-inflammatory effects. We further investigated the protective activity and anti-inflammatory mechanisms of 23OM18 in these two cell models. In addition, the profiles of 16 metabolites were compared between the representative accessions and among the five genetic resources using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). The results showed that 23OM18 protected HT22 cells by inhibiting reactive oxygen species generation and regulating the MAPK-JNK signaling pathway, thereby reducing LPS-induced BV2 cell neuroinflammation by regulating the NF-κB and MAPK signaling pathways. Based on these results, 23OM18 has the potential to be developed as a functional food for the treatment of neurodegenerative diseases.
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Affiliation(s)
- Linsha Dong
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; (L.D.); (H.L.); (Z.L.)
| | - Bo-Ram Choi
- Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea; (B.-R.C.); (D.Y.)
| | - Hyo Bong Jeong
- Department of Horticultural Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Wanju 55365, Republic of Korea; (H.B.J.); (H.E.L.)
| | - Hwan Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; (L.D.); (H.L.); (Z.L.)
| | - Zhiming Liu
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; (L.D.); (H.L.); (Z.L.)
| | - Dahye Yoon
- Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea; (B.-R.C.); (D.Y.)
| | - Hye Eun Lee
- Department of Horticultural Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Wanju 55365, Republic of Korea; (H.B.J.); (H.E.L.)
| | - Dong-Sung Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; (L.D.); (H.L.); (Z.L.)
| | - Dae Young Lee
- BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
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12
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Gu D, Xia Y, Ding Z, Qian J, Gu X, Bai H, Jiang M, Yao D. Inflammation in the Peripheral Nervous System after Injury. Biomedicines 2024; 12:1256. [PMID: 38927464 PMCID: PMC11201765 DOI: 10.3390/biomedicines12061256] [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: 04/28/2024] [Revised: 06/01/2024] [Accepted: 06/03/2024] [Indexed: 06/28/2024] Open
Abstract
Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways. Previously, inflammation was thought to be detrimental to the body, but further research has shown that appropriate inflammation promotes nerve regeneration, axon regeneration, and myelin formation. On the contrary, excessive inflammation can cause nerve tissue damage and pathological changes, and even lead to neurological diseases. Therefore, after nerve injury, various cells in the body interact with cytokines and chemokines to promote peripheral nerve repair and regeneration by inhibiting the negative effects of inflammation and harnessing the positive effects of inflammation in specific ways and at specific times. Understanding the interaction between neuroinflammation and nerve regeneration provides several therapeutic ideas to improve the inflammatory microenvironment and promote nerve regeneration.
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Affiliation(s)
- Dandan Gu
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Yiming Xia
- Medical School, Nantong University, Nantong 226001, China
| | - Zihan Ding
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Jiaxi Qian
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Xi Gu
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Huiyuan Bai
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Maorong Jiang
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
| | - Dengbing Yao
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China (H.B.)
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13
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Zhao P, Hou Y, Yan T, Kang J, Tian Y, Li J, Zeng C, Geng F, Liao Q. Synthesis and biological evaluation of chrysin derivatives containing α-lipoic acid for the treatment of inflammatory bowel disease. Front Chem 2024; 12:1406051. [PMID: 38860236 PMCID: PMC11163049 DOI: 10.3389/fchem.2024.1406051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 05/07/2024] [Indexed: 06/12/2024] Open
Abstract
This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 μM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.
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Affiliation(s)
- Pengyu Zhao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yusen Hou
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Tingting Yan
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, China
| | - Jie Kang
- Yunnan Shengke Pharmaceutical Co., Ltd., Kunming, China
| | - Ye Tian
- Guizhou Yunfeng Pharmaceutical Co., Ltd., Xingyi, China
| | - Jiaxin Li
- Sichuan Engineering Research Center for Medicinal Animals, Chengdu, China
| | - Chenjuan Zeng
- Guizhou Yunfeng Pharmaceutical Co., Ltd., Xingyi, China
| | - Funeng Geng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, China
| | - Qi Liao
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, China
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Fratianni F, Amato G, Ombra MN, De Feo V, Nazzaro F, De Giulio B. Chemical Characterization and Biological Properties of Leguminous Honey. Antioxidants (Basel) 2024; 13:482. [PMID: 38671929 PMCID: PMC11047671 DOI: 10.3390/antiox13040482] [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: 03/25/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 04/28/2024] Open
Abstract
Honey can beneficially act against different human diseases, helping our body to improve its health. The aim of the present study was first to increase knowledge of some biochemical characteristics (amount and composition of polyphenols and volatile organic compounds, vitamin C content) of five Italian legume honeys (alfalfa, astragalus, carob, indigo, and sainfoin). Furthermore, we evaluated their potential health properties by studying their antioxidant and in vitro anti-inflammatory activities and in vitro inhibitory effects on three enzymes involved in neurodegenerative diseases (acetylcholinesterase, butyrylcholinesterase, and tyrosinase). Alfalfa honey showed the highest total polyphenol content (TPC) (408 μg g-1 of product). Indigo honey showed the lowest TPC (110 μg g-1 of product). The antioxidant activity was noteworthy, especially in the case of sainfoin honey (IC50 = 6.08 mg), which also exhibited excellent inhibitory action against butyrylcholinesterase (74%). Finally, the correlation between the biochemical and functional results allowed us to identify classes of molecules, or even single molecules, present in these five honeys, which are capable of influencing the properties indicated above.
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Affiliation(s)
- Florinda Fratianni
- Institute of Food Science, CNR-ISA, Via Roma 64, 83100 Avellino, Italy; (F.F.); (M.N.O.); (V.D.F.); (B.D.G.)
| | - Giuseppe Amato
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy;
| | - Maria Neve Ombra
- Institute of Food Science, CNR-ISA, Via Roma 64, 83100 Avellino, Italy; (F.F.); (M.N.O.); (V.D.F.); (B.D.G.)
| | - Vincenzo De Feo
- Institute of Food Science, CNR-ISA, Via Roma 64, 83100 Avellino, Italy; (F.F.); (M.N.O.); (V.D.F.); (B.D.G.)
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy;
| | - Filomena Nazzaro
- Institute of Food Science, CNR-ISA, Via Roma 64, 83100 Avellino, Italy; (F.F.); (M.N.O.); (V.D.F.); (B.D.G.)
| | - Beatrice De Giulio
- Institute of Food Science, CNR-ISA, Via Roma 64, 83100 Avellino, Italy; (F.F.); (M.N.O.); (V.D.F.); (B.D.G.)
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Zhou L, Liu F, You J, Zhou B, Guo W, Qu W, Ren X, Gao G. A Novel Self-Pumping Janus Dressing for Promoting Wound Immunomodulation and Diabetic Wound Healing. Adv Healthc Mater 2024; 13:e2303460. [PMID: 37957786 DOI: 10.1002/adhm.202303460] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Indexed: 11/15/2023]
Abstract
Self-pumping dressings become one of the optimal solutions for the controlled management of chronic diabetic wound exudate and wound healing. However, present self-pumping dressings are not only prone to breakage of the loose hydrophobic layer but also have cumbersome and complicated preparation steps, which hinder the application of self-pumping dressings in diabetic wound treatment. Herein, a novel self-pumping structure of superabsorbent Janus dressing is designed to improve the strength of the hydrophobic layer and promote diabetic wound healing. The Janus dressing consists of a hydrophobic layer with a drainage agent (drainage layer) and a fluffy 3D nanofiber cotton (absorbent layer). Regardless of the thickness of the drainage layer, the drainage agent in the drainage layer provides the fluid to penetrate the drainage layer to the absorbent layer for unidirectional fluid draining. In design proof, the superabsorbent Janus dressing provides unidirectional drainage of inflammatory exudate and regulation of macrophage polarization, resulting in faster diabetic wound healing than single-layer dressings. Thus, the Janus dressing demonstrates important clinical implications to offer a novel design and preparation strategy for accelerating diabetic wound healing.
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Affiliation(s)
- Lubin Zhou
- Polymeric and Soft Materials Laboratory, Advanced Institute of Materials Science, School of Chemical Engineering, Changchun University of Technology, Changchun, 130012, P. R. China
| | - Fan Liu
- Polymeric and Soft Materials Laboratory, Advanced Institute of Materials Science, School of Chemical Engineering, Changchun University of Technology, Changchun, 130012, P. R. China
| | - Junyuan You
- Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, P. R. China
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130041, P. R. China
| | - Bo Zhou
- Polymeric and Soft Materials Laboratory, Advanced Institute of Materials Science, School of Chemical Engineering, Changchun University of Technology, Changchun, 130012, P. R. China
| | - Wenlai Guo
- Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, P. R. China
| | - Wenrui Qu
- Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, P. R. China
| | - Xiuyan Ren
- Polymeric and Soft Materials Laboratory, Advanced Institute of Materials Science, School of Chemical Engineering, Changchun University of Technology, Changchun, 130012, P. R. China
| | - Guanghui Gao
- Polymeric and Soft Materials Laboratory, Advanced Institute of Materials Science, School of Chemical Engineering, Changchun University of Technology, Changchun, 130012, P. R. China
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16
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Li S, Xiao H, Liu M, Wang Q, Sun C, Yao J, Cao N, Zhang H, Zhang G, Xiao X. Network pharmacology and experimental verification to explore the anti-superficial thrombophlebitis mechanism of Mailuo shutong pill. JOURNAL OF ETHNOPHARMACOLOGY 2024; 322:117668. [PMID: 38159829 DOI: 10.1016/j.jep.2023.117668] [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: 09/24/2023] [Revised: 12/13/2023] [Accepted: 12/25/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Mailuo shutong pill (MLST) has been widely used in clinical treatment of superficial thrombotic phlebitis (STP). Nevertheless, the major active components of MLST and the mechanism of synergistic action have not been reported. AIM OF THE STUDY The present study aimed to evaluate the improving effects and the underlying mechanism of MLST on mannitol-induced STP in rabbits. MATERIAL AND METHODS In this study, Ultrahigh-performance liquid chromatography electrospray ionization quadrupole-exactive orbitrap mass spectrometry (UHPLC-ESI-Q-Exactive-Orbitrap-MS) was used to analyze and identify the chemical composition of MLST and the prototype components absorbed into the blood. Then, according to the prototype components in serum, the targets and mechanisms of MLST were explored by applying network pharmacology. The rabbit model of STP was established by injecting 20% mannitol into bilateral auricular vein. The pathological changes of rabbit ear tissues, inflammatory factors, coagulation function and hemorheology were detected. In addition, molecular docking verified the interaction between the main active ingredient and the key target. Finally, the PI3K/AKT pathway and its regulated downstream pathways were verified by Western blot. RESULTS A total of 96 MLST components and 53 prototypical components absorbed into the blood were successfully identified. Based on network pharmacology, PI3K/AKT pathway and 10 chemical components closely related to this pathway were obtained. Hematoxylin-eosin (HE) staining results indicated that MLST effectively improved of the pathological damage of ear tissues. MLST decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and C-reactive protein (CRP). The expression of platelets (PLT) and fibrinogen concentration (FIB) was decreased, while prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. In addition, the plasma viscosity and whole blood viscosity in the MLST groups were significantly decreased. The more important discovery was that the expressions of P-PI3K, VEGF, P-AKT, P-IκB-α, P-NF-κB, NLRP3, ASC, Cleaved IL-1β and Cleaved Caspase-1 were effectively reversed after treatment with MLST. CONCLUSIONS This study comprehensively analyzed and characterized the chemical composition of MLST and the prototypical components absorbed into the blood. This study strongly confirmed the pharmacodynamic effect of MLST on STP. More importantly, this pharmacodynamic effect was achieved through inhibition of the PI3K/AKT pathway and its regulated NF-κB and NLRP3 pathways.
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Affiliation(s)
- Shirong Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - He Xiao
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
| | - Mingfei Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Qingguo Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Chenghong Sun
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
| | - Jingchun Yao
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
| | - Ningning Cao
- Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300250, China.
| | - Haifang Zhang
- Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Guimin Zhang
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
| | - Xuefeng Xiao
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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17
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Badders J, Coblens O, Ranasinghe V, Shabani S. Medical Honey in Head and Neck Cancer. Cureus 2024; 16:e52822. [PMID: 38406013 PMCID: PMC10884620 DOI: 10.7759/cureus.52822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2024] [Indexed: 02/27/2024] Open
Abstract
Medical honey has been recognized for its medicinal properties for thousands of years, and several medical honey products have entered the market over the last two decades. In vitro studies have shown that honey has antimicrobial properties, protects against bacterial growth, and improves wound healing. However, these products are not widely used for wound treatment in head and neck surgery. Additionally, honey has been utilized in those undergoing radiotherapy for head and neck cancer (HNC) to treat radiation-induced mucositis. This literature review aims to describe and assess the utility of medical honey for patients undergoing treatment for HNC and thus review publications on medical honey for treating postoperative wounds and preventing radiation-induced mucositis. Ovid (Medicine), PubMed (Medline), and Google Scholar were searched using keywords related to medical honey and HNC. All abstracts retrieved in the search were screened for content relevance. Three randomized controlled trials on wound healing were reviewed and assigned a score using the revised Cochrane risk of bias tool for methodological quality. Three meta-analyses assessing radiation-induced mucositis were reviewed and evaluated. Using medical honey on postoperative wounds was associated with shorter hospital stays, faster healing of palatal graft defects, and reduced pigmentation of thyroidectomy scars. Medical honey had no impact on bacterial culture rates or other aesthetic measures. For patients undergoing radiation for HNC, orally ingested honey was associated with less weight loss and delayed the onset of severe radiation-induced mucositis. However, results across different meta-analyses were mixed. Minimal evidence supporting the use of honey in postoperative wounds for patients with HNC exists. However, the studies reviewed here, combined with in-vitro studies and studies in other anatomical regions, show honey may offer some wound healing benefits. More robust studies are needed to confirm the potential benefits of medical honey in the postoperative wounds of HNC patients. While radiation-induced mucositis continues to be a debilitating adverse effect of HNC treatment, the literature reviewed supports honey as a safe complementary therapy in preventing radiation-induced mucositis.
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Affiliation(s)
- Joel Badders
- School of Medicine, University of Texas Medical Branch, Galveston, USA
| | - Orly Coblens
- Otolaryngology, University of Texas Medical Branch, Galveston, USA
| | - Viran Ranasinghe
- Otolaryngology, University of Texas Medical Branch, Galveston, USA
| | - Sepehr Shabani
- Otolaryngology, University of Texas Medical Branch, Galveston, USA
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Magoshi IB, Nekhumbe AW, Ibrahim MA, Serem JC, Bester MJ. Gastrointestinal Effects on the Antioxidant and Immunomodulatory Properties of South African Fynbos Honey. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2023; 2023:2553197. [PMID: 38045104 PMCID: PMC10691895 DOI: 10.1155/2023/2553197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 10/20/2023] [Accepted: 11/02/2023] [Indexed: 12/05/2023]
Abstract
The Fynbos biome, Western Cape Province, South Africa, produces a unique honey from Apis mellifera capensis. The bioactivity of Fynbos (FB1-FB6) honeys and Manuka, unique manuka factor 15+ (MAN UMF15+) honey subjected to simulated in vitro digestion, was compared. The effect of each phase of digestion on the antioxidant properties and nitric oxide- (NO-) associated immunomodulatory effects was determined. The total phenolic content of MAN (UMF15+) was higher than that of FB honeys, and following digestion, the percentage bioaccessibility (BA) was 68.6% and 87.1 ± 27.0%, respectively. With the Trolox equivalent antioxidant capacity assay, the activity of FB1 and FB6 was similar to MAN (UMF15+) but reduced for FB2, FB3, FB4, and FB5 with a %BA of 77.9% for MAN (UMF15+) and 78.2 ± 13.4% for FB. The oxygen radical absorbance capacity of MAN (UMF15+) and FB honeys was similar and unaltered with digestion. In a cellular environment, using colon adenocarcinoma (Caco-2) cells, both undigested and the gastric digested honey reduced 2,2'-azobis-(2-amidinopropane) dihydrochloride- (AAPH-) mediated peroxyl radical formation. In contrast, following gastroduodenal digestion, the formation of reactive oxygen species (ROS) was increased. In murine macrophage (RAW 264.7) cells, all honeys induced different levels of NO which was significantly increased with digestion for MAN (UMF15+) and FB1. In LPS/IFN-γ stimulated RAW 264.7 macrophages, only undigested MAN (UMF15+) effectively reduced NO levels, and with digestion, NO scavenging activity of MAN (UMF15+) was reduced but increased for FB5 and FB6. In a noncellular environment, MAN (UMF15+), FB1, FB2, and FB6 scavenged NO, and with digestion, this activity was maintained. This study has identified that undigested and gastric-digested FB honey has antioxidant properties with strong potential anticancer effects following gastroduodenal digestion, related to ROS formation. MAN (UMF15+) had anti-inflammatory effects which were lost postdigestion, and in contrast, FB5 and FB6 had anti-inflammatory effects postdigestion.
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Affiliation(s)
| | | | | | - June Cheptoo Serem
- Department of Anatomy, University of Pretoria, Pretoria 002, South Africa
| | - Megan Jean Bester
- Department of Anatomy, University of Pretoria, Pretoria 002, South Africa
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Pan HY, Wang XW, He QX, Lu YD, Zhang WY, Jin JW, Lin B. Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis. World J Gastrointest Oncol 2023; 15:1988-1997. [DOI: 10.4251/wjgo.v15.i11.1988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/19/2023] [Accepted: 09/27/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial.
AIM To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage.
METHODS The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg’s test for publication bias was performed using Stata 13.0 software.
RESULTS Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg’s test revealed no significant publication bias.
CONCLUSION The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage.
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Affiliation(s)
- Hai-Yan Pan
- Department of Emergency Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Xiao-Wei Wang
- Department of Cardiopulmonary Rehabilitation, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Qiong-Xiao He
- Department of Emergency Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Yi-Dan Lu
- Department of Ultrasound, Zhejiang Cancer Hospital, Hangzhou 310005, Zhejiang Province, China
| | - Wan-Yi Zhang
- Department of Emergency Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Jian-Wei Jin
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Bin Lin
- Department of Emergency Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
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20
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Sun C, Peng S, Lv Z, Guo T, Zhang L. Research of STEAP3 interaction with Rab7A and RACK1 to modulate the MAPK and JAK/STAT signaling in Osteoarthritis. Int Immunopharmacol 2023; 124:111034. [PMID: 37820423 DOI: 10.1016/j.intimp.2023.111034] [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: 06/28/2023] [Revised: 10/03/2023] [Accepted: 10/04/2023] [Indexed: 10/13/2023]
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. The molecular mechanisms underlying OA progression remain incompletely understood. In this study, we investigated the role of STEAP3 (Six Transmembrane Epithelial Antigen of the Prostate 3) in the development of OA. Our results demonstrated that STEAP3 was upregulated in OA cartilage tissues and contributes to the progression of the disease. To elucidate the mechanism, we employed transcriptomic and interaction proteomics analysis, and identified dysregulated genes and pathways associated with STEAP3 overexpression. Specifically, we found that STEAP3 interacted with Rab7A, a protein involved in intracellular trafficking and autophagy, and suppressed its activity. In addition, STEAP3 interacted with activated C kinase 1 (RACK1) and enhanced its activity. Furthermore, our data indicated that the suppression of Rab7A activity by STEAP3 promoted the activation of receptor tyrosine kinases (RTKs) and the promoting effects of RACK1 by STEAP3, both of which in turn activated the MAPK and JAK/STAT signaling pathways. In conclusion, our findings highlighted the role of STEAP3 in promoting OA progression. By inhibiting Rab7A activity and promoting RACK1 activity, STEAP3 enhanced inflammation through the activation of RTKs and subsequent activation of the MAPK and JAK/STAT signaling pathways. Targeting STEAP3 may provide a potential therapeutic strategy for the treatment of OA by modulating these interconnected pathways.
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Affiliation(s)
- Chang Sun
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Song Peng
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Zhongyang Lv
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Ting Guo
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Lei Zhang
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
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Sun KX, Xu RQ, Rong H, Pang HY, Xiang TX. Prognostic significance of the Gustave Roussy immune (GRIm) score in cancer patients: a meta-analysis. Ann Med 2023; 55:2236640. [PMID: 37851510 PMCID: PMC10586078 DOI: 10.1080/07853890.2023.2236640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/07/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients. METHODS Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis. RESULTS Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73-2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22-1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results. CONCLUSION Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.
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Affiliation(s)
- Ke-Xin Sun
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ru-Qin Xu
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huan Rong
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Hua-Yang Pang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Ting-Xiu Xiang
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
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Duncan JBW, Basu S, Vivekanand P. Honey gold nanoparticles attenuate the secretion of IL-6 by LPS-activated macrophages. PLoS One 2023; 18:e0291076. [PMID: 37682929 PMCID: PMC10490926 DOI: 10.1371/journal.pone.0291076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine that coordinates host immune responses to infection. Though essential to the acute phase response, prolonged IL-6-mediated recruitment of mononuclear cells has been implicated in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. Accordingly, identifying novel therapeutics that diminish circulating IL-6 levels could benefit individuals suffering from chronic inflammation. In immunocompetent hosts, bacterial lipopolysaccharide (LPS) recognition by toll-like receptor 4 (TLR4) activates the transcription factor NF-κB, driving macrophage production of IL-6. Interestingly, both citrate-stabilized and 'green' synthesized gold nanoparticles (AuNPs) have been shown to modulate the cytokine responses of LPS-activated macrophages. Here we demonstrate that AuNPs, synthesized with commercial and locally sourced honey, downregulate LPS-induced macrophage secretion of IL-6. Compared to LPS-only controls, inhibition of IL-6 levels was observed for all three types of honey AuNPs. The effect was likely driven by honey AuNP-mediated perturbation of the TLR4/NF-κB signaling pathway, as evidenced by a reduction in the phosphorylation of IκB. Further investigation into the anti-inflammatory properties of honey AuNPs may yield novel therapeutics for the treatment of chronic inflammation.
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Affiliation(s)
- John Benjamin W. Duncan
- Department of Biology, Susquehanna University, Selinsgrove, Pennsylvania, United States of America
| | - Swarna Basu
- Department of Chemistry, Susquehanna University, Selinsgrove, Pennsylvania, United States of America
| | - Pavithra Vivekanand
- Department of Biology, Susquehanna University, Selinsgrove, Pennsylvania, United States of America
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23
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Yee N, Kim H, Kim E, Cha YH, Ma L, Cho NE, Kim D, Kim CY, Kim SH, Ryoo Z, Yi J, Kim MO. Effects of Sangju Honey on Oral Squamous Carcinoma Cells. J Cancer Prev 2022; 27:239-246. [PMID: 36713940 PMCID: PMC9836912 DOI: 10.15430/jcp.2022.27.4.239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/27/2022] [Accepted: 12/27/2022] [Indexed: 01/11/2023] Open
Abstract
Since ancient times, honey has been used in traditional medicine owing to its pharmacological effects. It possesses anticancer properties. However, the therapeutic implications of Sangju honey in cancer remains unknown. Therefore, we aimed to demonstrate the potential anticancer effects of Sangju honey on human oral squamous cell carcinoma (OSCC), particularly focusing on epithelial-mesenchymal transition (EMT) and apoptotic and mitogen-activated protein kinase (MAPK) signaling pathways. Ca9-22 and YD-10B human OSCC cells were treated with 0.25% or 0.5% Sangju honey, and the cell viability was examined using the Cell Counting Kit-8 assay. Cell morphology studies were conducted to observe morphological changes, and the wound-healing assay was performed to evaluate the proliferation of honey-treated OSCC cells. Western blot analysis was conducted to investigate protein expression related to EMT and apoptotic and MAPK signaling pathways. Sangju honey reduced cell viability, induced morphological changes, and significantly suppressed the proliferation and migration of Ca9-22 and YD-10B cells. The expression of E-cadherin and N-cadherin was increased and decreased, respectively, in both OSCC cell lines. Moreover, Sangju honey stimulated apoptosis by increasing the expression of p21, p53, cleaved caspase 3, and caspase 9. Furthermore, it downregulated the expression of phospho (p)-extracellular signal-regulated kinases 1 and 2, p-c-Jun amino-terminal kinase, and p-p38 in Ca9-22 and YD-10B cells. Sangju honey inhibits Ca9-22 and YD-10B cell proliferation by regulating EMT, inducing apoptosis, and suppressing the MAPK signaling pathway. Thus, it is a potential anticancer agent for human OSCC.
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Affiliation(s)
- Nangwon Yee
- Department of Animal Biotechnology, Kyungpook National University, Sangju, Korea
| | - Hyeonjin Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Eungyung Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Yong Ho Cha
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Lei Ma
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Na Eun Cho
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Dongwook Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Chae Yeon Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea
| | - Sung-Hyun Kim
- Department of Bio-Medical Analysis, Korea Polytechnic College, Nonsan, Korea
| | - Zaeyoung Ryoo
- School of Life Science, Kyungpook National University, Daegu, Korea,Zaeyoung Ryoo, E-mail: , https://orcid.org/0000-0001-6993-3624
| | - Junkoo Yi
- Gyeongsangbukdo Livestock Institute Research, Yeongju, Korea,Junkoo Yi, E-mail: , https://orcid.org/0000-0003-2593-6529
| | - Myoung Ok Kim
- Department of Animal Biotechnology, Kyungpook National University, Sangju, Korea,Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea,Correspondence to Myoung Ok Kim, E-mail: , https://orcid.org/0000-0001-6650-7734
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Zhong Y, Chen Y, Pan Z, Tang K, Zhong G, Guo J, Cui T, Li T, Duan S, Yang X, Gao Y, Wang Q, Zhang D. Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress. Front Pharmacol 2022; 13:1027731. [PMID: 36278209 PMCID: PMC9585238 DOI: 10.3389/fphar.2022.1027731] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/21/2022] [Indexed: 11/13/2022] Open
Abstract
Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.
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Affiliation(s)
- Yadi Zhong
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yingjian Chen
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhisen Pan
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kaijia Tang
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guangcheng Zhong
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jingyi Guo
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tianqi Cui
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tianyao Li
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Siwei Duan
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoying Yang
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China
| | - Yong Gao
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qi Wang
- Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Dong Zhang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
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Zheng X, Zhao Y, Naumovski N, Zhao W, Yang G, Xue X, Wu L, Granato D, Peng W, Wang K. Systems Biology Approaches for Understanding Metabolic Differences Using 'Multi-Omics' Profiling of Metabolites in Mice Fed with Honey and Mixed Sugars. Nutrients 2022; 14:3445. [PMID: 36014951 PMCID: PMC9412287 DOI: 10.3390/nu14163445] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 12/17/2022] Open
Abstract
Honey is proposed to be the oldest natural sweetener and it is a standard component of several dietary patterns. Recent evidence suggests that replacing sugars, such as fructose, with honey has potential health benefits. In this study, we determined the effects of honey supplementation in mice on cardiometabolic and inflammatory markers and changes in gut microbiota and metabolomic profiles. We compared mice fed a honey diet (1 or 2 g/kg) with those fed an analog diet (mixed fructose, glucose, and sucrose (FSG) solutions) at exact dosages for one month. We found the same blood glucose fluctuating trends for honey- and FGS-fed mice. The honey diets resulted in less weight gain and fewer ballooned hepatocytes. Additionally, honey diets decreased the total serum cholesterol and TNF-α and increased the antioxidant enzyme activity. Each diet type was associated with distinct gut microbiota and metabolomics profiles. Systems biology analysis revealed that Lactococcus spp., Lachnospiraceae spp., and oleamide had the strongest correlations with lipid metabolic networks. Although in an animal model, this study provides a good understanding of the potential benefits of choosing honey rather than mixed sugars in regular dietary patterns.
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Affiliation(s)
- Xing Zheng
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Yazhou Zhao
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Nenad Naumovski
- University of Canberra Health Research Institute (UCHRI), University of Canberra, Locked Bag 1, Bruce, Canberra, ACT 2601, Australia
| | - Wen Zhao
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Guan Yang
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Kowloon, Hong Kong 999077, China
| | - Xiaofeng Xue
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Liming Wu
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Daniel Granato
- Department of Biological Sciences, School of Natural Sciences, Faculty of Science and Engineering, University of Limerick, V94 T9PX Limerick, Ireland
| | - Wenjun Peng
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Kai Wang
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
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Ahmed ASAA, Eltregy S, Kandil MI. Honey dressing: a missed way for orthopaedic wound care. INTERNATIONAL ORTHOPAEDICS 2022; 46:2483-2491. [PMID: 35971015 PMCID: PMC9556393 DOI: 10.1007/s00264-022-05540-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/04/2022] [Indexed: 01/16/2023]
Abstract
Purpose Orthopaedic-related wounds are critical situations calling for care to avoid deep infections and its consequences. The purpose of this study was to evaluate the efficacy of using honey for care of orthopaedic-related wounds with limited resources. Patients and methods This prospective study included 50 cases with an average age of 38.18 (range 17–63) years with 38 males and 12 females. The most frequent wound location was the leg (41 patients; 82%), then the foot (six patients; 12%), and the ankle in three patients (6%). The aetiologies were open fractures (34 cases; 68%), infected tibial non-unions (nine cases; 18%), and post-operative infections (seven cases; 14%). Exposed tendon was present in three cases. Bone exposure was present in two cases. Deep infection was present in 29 cases (58%). Besides treating the primary cause, a ribbon of gauze soaked with honey was applied to the wounds after thorough saline washing. Results Wound sizes were variable. All cases showed improvement in all parameters with complete wound healing and full coverage of bone and tendons. Recurrence of deep infection occurred in three cases and treated by debridement. One case needed sequestrectomy of a small exposed tibial cortical fragment. Exposed tendon cases showed superficial necrosis which was treated by simple debridement. Initial mild itching occurred in five patients with spontaneous resolution. Conclusion With treating the underlying aetiology and optimising the patient’s general condition, honey was an effective, simple, and affordable method of wound care in different orthopaedic conditions even with exposed bone or tendons.
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Affiliation(s)
- Abdel-Salam Abdel-Aleem Ahmed
- Department of Orthopaedic Surgery, Benha Faculty of Medicine, Benha University, Farid Nada Street, Kalyubia, Benha, Post Office 13518 Egypt
| | - Sherif Eltregy
- Department of Orthopaedic Surgery, Benha Faculty of Medicine, Benha University, Farid Nada Street, Kalyubia, Benha, Post Office 13518 Egypt
| | - Mahmoud Ibrahim Kandil
- Department of Orthopaedic Surgery, Benha Faculty of Medicine, Benha University, Farid Nada Street, Kalyubia, Benha, Post Office 13518 Egypt
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Wang XS, Peng MJ, He CT. The antihypertensive effects of Eucommia ulmoides leaf water/ethanol extracts are chlorogenic acid dependent. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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28
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Ellagic acid (EA), a tannin was isolated from Eucalyptus citriodora leaves and its anti-inflammatory activity. Med Chem Res 2021. [DOI: 10.1007/s00044-021-02806-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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