Lumbar disc degeneration due to annulus fibrosus (AF) defects poses a significant challenge in clinical treatment Current treatments exhibit limited repair efficacy and a high recurrence rate. To address this, we devised a novel approach of crosslinking stabilization strategy. We integrated fibrinogen, thrombin, genipin, and human bone marrow-derived mesenchymal stem cells (hBMSCs) hydrogel (FTGB) with acellular scaffold and fascia (FTGB@S@F) to remediate AF defects. FTIR analysis confirmed stable chemical crosslinking within the FTGB hydrogel. FTGB hydrogel demonstrated superior biocompatibility compared to the FB hydrogel, with significantly higher cell viability (97.60 ± 2.02 % vs 81.43 ± 4.50 %, P < 0.01) and enhanced proliferation and migration, as shown in DAPI, Edu and phalloidin staining. Atomic force microscopy (AFM) revealed that FTGB@S has a dense reticular structure, enhancing material performance with higher elastic modulus than FB@S. MTS testing showed that FTGB@S@F outperformed other groups in resisting cyclic axial load (25.53 ± 1.17 MPa) and maintaining disc height (0.57 ± 0.12 mm), with stable axial compression resistance and minimal deformation. It also exhibited the lowest rupture ROM (1.45 ± 0.17 mm) and a rupture modulus close to the Intact control, demonstrating its potential to restore AF mechanical function. MRI imaging revealed that the FTGB@S@F group preserved an intact AF structure with high signal intensity, a significantly larger NP area (223.64 ± 73.32 mm2 vs 137.30 ± 75.31 mm2, P < 0.05), and higher disc height (102.5 ± 73.32 % vs 88.50 ± 12.86 %, P < 0.05). Histology confirmed superior AF repair and reduced NP degeneration in the FTGB@S@F group compared to the Un-repair and FB@S@F groups. Transcriptomic analysis identified upregulation of PIGR and downregulation of COL4A3, linked to the PI3K-Akt pathway. Immunohistochemical and qPCR analyses showed enhanced expression of COL1, Aggrecan, and RhoA, indicating effective regeneration.

Reproductive disorders, including preeclampsia (PE), endometriosis, premature ovarian failure (POF), and polycystic ovary syndrome (PCOS), present substantial challenges to women's reproductive health. Exosomes (EXOs) are cell-derived vesicles containing molecules that influence target cells' gene expression and cellular behavior. Among their cargo, microRNAs (miRNAs)-short, non-coding RNAs typically 19-25 nucleotides in length-play a crucial role in post-transcriptional gene regulation and have been extensively studied for their therapeutic potential. miRNAs are considered therapeutic targets because they regulate key cellular pathways such as proliferation, apoptosis, angiogenesis, and tissue repair. This review examines the role of exosomal miRNAs from sources such as mesenchymal stem cells (MSCs), plasma, and amniotic fluid in female reproductive disorders, including PE, POF, PCOS, and endometriosis. We discuss their biological origins, mechanisms of miRNA sorting and packaging, and their therapeutic applications in modulating disease progression. By categorizing miRNAs according to their beneficial or detrimental effects in specific conditions, we aim to simplify the understanding of their roles in female infertility.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Intervertebral disc degeneration is the leading cause of low back pain, imposing significant burdens on patients, societies, and economies. Advancements in regenerative medicine have spotlighted extracellular vesicles as promising nanoparticles for intervertebral disc degeneration treatment. Extracellular vesicles retain the potential of cell therapy and serve as carriers to deliver their cargo to target cells, thereby regulating cell activity. This review summarizes the biogenesis and molecular composition of extracellular vesicles and explores their therapeutic roles in intervertebral disc degeneration treatment through various mechanisms. These mechanisms include mitigating cell loss and senescence, delaying extracellular matrix degeneration, and modulating the inflammatory microenvironment. Additionally, it highlights recent efforts in engineering extracellular vesicles to enhance their targeting and therapeutic efficacy. The integration of extracellular vesicle-based acellular therapy is anticipated to drive significant advancements in disc regenerative medicine.

Existing clinical treatment strategies often fail to effectively address the challenges associated with regenerating degenerated intervertebral discs. As a new regenerative medicine strategy, the extracellular vesicle strategy avoids the risks associated with cell transplantation and shows great promise in treating intervertebral disc degeneration by carrying therapeutic cargo. This review comprehensively examines the latest research, underlying mechanisms, and therapeutic potential of extracellular vesicles, offering a promising new strategy for intervertebral disc degeneration treatment.

Intervertebral disc degeneration (IDD) causes a variety of symptoms such as low back pain, disc herniation, and spinal stenosis, which can lead to high social and economic costs. Alpinetin has an anti-inflammatory potential, but its effect on IDD is unclear. Herein, we investigated the effect of alpinetin on IDD. To mimic an in vitro model of IDD, nucleus pulposus cells (NPCs) were exposed to interleukin 1β (IL-1β). The viability of NPCs was assessed by CCK-8 assay. The expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), aggrecan, collagen-2, and matrix metalloproteinase-3 (MMP-3) was examined by qRT-PCR and western blotting. The protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated protein X (Bax), and cleaved caspase-3 were scrutinized by western blotting. The flow cytometry assay was performed to assess apoptosis of NPCs. The contents of inflammatory factors were examined by ELISA kits. Results showed that alpinetin repressed IL-1β-tempted activation of the TLR4/MyD88 pathway and apoptosis in NPCs. Alpinetin alleviated IL-1β-tempted inflammatory responses and oxidative stress in NPCs. Moreover, alpinetin lessened IL-1β-tempted extracellular matrix (ECM) degeneration in NPCs by enhancing the expression of aggrecan and collagen-2 and reducing the expression of MMP-3. The effects of alpinetin on IL-1β-exposed NPCs were neutralized by TLR4 upregulation. In conclusion, alpinetin repressed IL-1β-tempted apoptosis, inflammatory responses, oxidative stress, and ECM degradation in NPCs through the inactivation of the TLR4/MyD88 pathway.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Skeletal diseases impose a considerable burden on society. The clinical and tissue-engineering therapies applied to alleviate such diseases frequently result in complications and are inadequately effective. Research has shifted from conventional therapies based on mesenchymal stem cells (MSCs) to exosomes derived from MSCs. Exosomes are natural nanocarriers of endogenous DNA, RNA, proteins, and lipids and have a low immune clearance rate and good barrier penetration and allow targeted delivery of therapeutics. MSC-derived exosomes (MSC-exosomes) have the characteristics of both MSCs and exosomes, and so they can have both immunosuppressive and tissue-regenerative effects. Despite advances in our knowledge of MSC-exosomes, their regulatory mechanisms and functionalities are unclear. Here we review the therapeutic potential of MSC-exosomes for skeletal diseases.

Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD. On the one hand, Se-Met promoted the production of EVs by enhancing the autophagy activity of MSCs. On the other hand, Se-Met pretreated MSC-derived EVs (Se-EVs) exhibited an enhanced protective effects on alleviating nucleus pulposus cells (NPCs) senescence and attenuating IDD compared with EVs isolated from control MSCs (C-EVs) in vitro and in vivo. Moreover, we performed a miRNA microarray sequencing analysis on EVs to explore the potential mechanism of the protective effects of EVs. The result indicated that miR-125a-5p is markedly enriched in Se-EVs compared to C-EVs. Further in vitro and in vivo experiments revealed that knockdown of miR-125a-5p in Se-EVs (miRKD-Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miROE-Se-EVs) boosted the protective effects. In conclusion, Se-Met facilitated the MSC-derived EVs production and increased miR-125a-5p delivery in Se-EVs, thereby improving the protective effects of MSC-derived EVs on alleviating NPCs senescence and attenuating IDD.

Bone repair in elderly patients poses a huge challenge due to the age-related progressive decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Bioactive scaffolds have been applied in bone regeneration due to their various biological functions. In this study, we aimed to fabricate functionalized bioactive scaffolds through loading osteoinductive extracellular vesicles (OI-EVs) based on mesoporous bioactive glass (MBG) scaffolds (1010 particles/scaffold) and to investigate its effects on osteogenesis and senescence of BMSCs. The results suggested that OI-EVs upregulate the proliferative and osteogenic capacities of senescent BMSCs. More importantly, The results showed that loading OI-EVs into MBG scaffolds achieved better bone regeneration. Furthermore, OI-EVs and BMSCs RNAs bioinformatics analysis indicated that OI-EVs play roles through transporting pivotal lncRNA acting as a "sponge" to compete with Mob3a for miR-1843a-5p to promote YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. Collectively, these results suggested that the OI-EVs lncRNA ceRNA regulatory networks might be the key point for senescent osteogenesis. More importantly, the study indicated the feasibility of loading OI-EVs into scaffolds and provided novel insights into biomaterial design for facilitating bone regeneration in the treatment of senescent bone defects. STATEMENT OF SIGNIFICANCE: Constructing OI-EVs/MBG delivering system and verification of its bone regeneration enhancement in senescent defect repair. Aging bone repair poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of BMSCs. OI-EVs/MBG delivering system were expected as promising treatment for senescent bone repair, which could provide an effective strategy for bone regeneration in elderly patients. Clarification of potential OI-EVs lncRNA ceRNA regulatory mechanism in senescent bone regeneration OI-EVs play important roles through transferring lncRNA-ENSRNOG00000056625 sponging miR-1843a-5p that targeted Mob3a to activate YAP translocation into nucleus, ultimately alleviate senescence, promote proliferation and osteogenic differentiation in O-BMSCs, which provides theoretical basis for EVs-mediated therapy in future clinical works.

Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.

Intervertebral disc (ID) degeneration (IDD) is one of the main causes of chronic low back pain, and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID. The environment in which the ID is located is harsh, with almost no vascular distribution within the disc, and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate. The stability of its internal environment also plays an important role in preventing IDD. The main feature of disc degeneration is a decrease in the number of cells. Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner. The main purpose is to promote their regeneration. The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix. The treatment of disc degeneration with stem cells has achieved good efficacy, and the current challenge is how to improve this efficacy. Here, we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles, enhancement of therapeutic effects when stem cells are mixed with related substances, and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions. We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.

Triple-negative breast cancer (TNBC) represents a challenging and aggressive form of breast cancer associated with limited treatment options and poor prognosis. Although chemotherapy is a primary therapeutic approach, drug resistance often hinders treatment success. However, the expanding knowledge of TNBC subtypes and molecular biology has paved the way for targeted therapies. Notably, exosomes (extracellular vesicles) have emerged as crucial carriers of tumorigenic factors involved in oncogenesis and drug resistance, facilitating cell-to-cell communication and offering potential as self-delivery systems. Among the cargo carried by exosomes, microRNAs (miRNAs) have gained attention due to their ability to mediate epigenetic changes in recipient cells upon transfer. Research has confirmed dysregulation of exosomal miRNAs in breast cancer cells compared to healthy cells, establishing them as promising biomarkers for cancer diagnosis and prognosis. In this comprehensive review, we summarize the latest research findings that underscore the diagnostic and prognostic significance of exosomal miRNAs in TNBC treatment. Furthermore, we explore contemporary therapeutic approaches utilizing these exosomal miRNAs for the benefit of TNBC patients, shedding light on potential breakthroughs in TNBC management.

Nucleus pulposus stem cells (NPSCs) senescence plays a critical role in the progression of intervertebral disc degeneration (IDD). Stem cell-derived extracellular vesicles (EV) alleviate cellular senescence. Whereas, the underlying mechanism remains unclear. Low stability largely limited the administration of EV in vivo. RGD, an arginine-glycine-aspartic acid tripeptide, strongly binds integrins expressed on the EV membranes, allowing RGD to anchor EV and prolong their bioavailability. An RGD-complexed nucleus pulposus matrix hydrogel (RGD-DNP) is developed to enhance the therapeutic effects of small EV (sEV). RGD-DNP prolonged sEV retention in vitro and ex vivo. sEV-RGD-DNP promoted NPSCs migration, decreased the number of SA-β-gal-positive cells, alleviated cell cycle arrest, and reduced p16, p21, and p53 activation. Small RNA-seq showed that miR-3594-5p is enriched in sEV, and targets the homeodomain-interacting protein kinase 2 (HIPK2)/p53 pathway. The HIPK2 knockdown rescues the impaired therapeutic effects of sEV with downregulated miR-3594-5p. RGD-DNP conjugate with lower amounts of sEV achieved similar disc regeneration with free sEV of higher concentrations in DNP. In conclusion, sEV-RGD-DNP increases sEV bioavailability and relieves NPSCs senescence by targeting the HIPK2/p53 pathway, thereby alleviating IDD. This work achieves better regenerative effects with fewer sEV and consolidates the theoretical basis for sEV application for IDD treatment.

To explore the repair effect of tissue engineering for annulus fibrosus (AF) injury in stress-stimulation environment.

Non-adhesive fibrinogen (Fib) representing the repair with non-stress stimulation and adhesive hydrogel of fibrinogen, thrombin and genipin mixture (Fib-T-G) representing the repair with stress stimulation were prepared to repair the AF lesion. The relationship between adhesion and stress stimulation was studied in rheological measurements, tension tests and atomic force microscopy (AFM) experiments. The repair effect of stress stimulation was studied in designed acellular AF scaffold models with fissures and defects. The models were repaired by the two different hydrogels, then implanted subcutaneously and cultured for 21 ​d in rats. Histology and qPCR of COL1A1, COL2A1, aggrecan, RhoA, and ROCK of the tissue engineering of the interface were evaluated afterward. Moreover, the repair effect was also studied in an AF fissure model in caudal disc of rats by the two different hydrogels. Discs were harvested after 21 ​d, and the disc degeneration score and AF healing quality were evaluated by histology.

In interfacial stress experiment, Fib-T-G hydrogel showed greater viscosity than Fib hydrogel (24.67 ​± ​1.007 vs 459333 ​± ​169205 ​mPa ​s). Representative force-displacement and sample modulus for each group demonstrate that Fib-T-G group significantly increased the interfacial stress level and enhanced the modulus of samples, compared with Fib group (P ​< ​0.01). The Fib-T-G group could better bond the interface to resist the loading strain force with the broken point at 1.11 ​± ​0.10 ​N compared to the Fib group at 0.12 ​± ​0.08 ​N ​(P ​< ​0.01). Focusing on the interfacial healing in acellular AF scaffold model, compared with Fib ​+ ​MSCs group, the fissure and defect were connected closely in Fib-T-G ​+ ​MSCs group (P ​< ​0.01). Relative higher gene expression of COL2A1 and RhoA in Fib-T-G ​+ ​MSCs group than Fib ​+ ​MSCs group in AF fissure and AF defect model (P ​< ​0.05). The immunohistochemistry staining showed more positive staining of COL2A1 and RhoA in Fib-T-G ​+ ​MSCs group than in Fib ​+ ​MSCs group in both AF fissure and AF defect models. The degree of disc degeneration was more severe in Fib ​+ ​MSCs group than Fib-T-G ​+ ​MSCs group in vivo experiment (11.80 ​± ​1.11 vs 7.00 ​± ​1.76, P ​< ​0.01). The dorsal AF defect in Fib-T-G ​+ ​MSCs group (0.02 ​± ​0.01 ​mm²) was significantly smaller than that (0.13 ​± ​0.05 ​mm²) in Fib ​+ ​MSCs group (P ​< ​0.05). Immunohistochemical staining showed more positive staining of COL2A1 and Aggrecan in Fib-T-G ​+ ​MSCs group than in Fib ​+ ​MSCs group.

Genipin crosslinked hydrogel can bond the interface of AF lesions and transfer strain force. Stress stimulation maintained by adhesive hydrogel promotes AF healing.

We believe the effect of stress stimulation could be concluded through this study and provides more ideals in mechanical effects for further research, which is a key technique for repairing intervertebral disc in clinic. The adhesive hydrogel of Fib-T-G+MSCs has low toxicity and helps bond the interface of AF lesion and transfer strain force, having great potential in the repair of AF lesion.

Stabilization of bone structure and function involves multiple cell-to-cell and molecular interactions, in which the regulatory functions of post-translational modifications such as ubiquitination and deubiquitination shouldn't be underestimated. As the largest family of deubiquitinating enzymes, the ubiquitin-specific proteases (USPs) participate in the development of bone homeostasis and bone-related diseases through multiple classical osteogenic and osteolytic signaling pathways, such as BMP/TGF-β pathway, NF-κB/p65 pathway, EGFR-MAPK pathway and Wnt/β-catenin pathway. Meanwhile, USPs may also broadly regulate regulate hormone expression level, cell proliferation and differentiation, and may further influence bone homeostasis from gene fusion and nuclear translocation of transcription factors. The number of patients with bone-related diseases is currently enormous, making exploration of their pathogenesis and targeted therapy a hot topic. Pathological increases in the levels of inflammatory mediators such as IL-1β and TNF-α lead to inflammatory bone diseases such as osteoarthritis, rheumatoid arthritis and periodontitis. While impaired body metabolism greatly increases the probability of osteoporosis. Abnormal physiological activity of bone-associated cells results in a variety of bone tumors. The regulatory role of USPs in bone-related disease has received particular attention from academics in recent studies. In this review, we focuse on the roles and mechanisms of USPs in bone homeostasis and bone-related diseases, with the expectation of informing targeted therapies in the clinic.

Here, we reported the biosynthesis of silver nanoparticles (AgNPs) using Urtica dioica (nettle) leaf extract as green reducing and capping agents and investigate their anticancer and antibacterial, activity. The Nettle-mediated biosynthesized AgNPs was characterized by UV-Vis a spectrophotometer. Their size, shape and elemental analysis were determined with the using of SEM and TEM. The crystal structure was determined by XRD and the biomolecules responsible for the reduction of Ag⁺ were determined using FTIR analysis. Nettle-mediated biosynthesis AgNPs indicated strong antibacterial activity against pathogenic microorganisms. Again, the antioxidant activity of AgNPs is quite high when compared to ascorbic acid. Anticancer effect of AgNPs, IC₅₀ dose was determined by XTT analysis using MCF-7 cell line and the IC₅₀ value was found to be 0.243 ± 0.014 μg/mL (% w/v).

This study aimed to evaluate the potential of mesenchymal stem cell-derived exosomes loaded with curcumin (Curc-Exos) as an effective therapeutic strategy for rheumatoid arthritis through modulation of proliferation and inflammatory response in HIG-82 synovial cells. For this purpose, Exos were isolated and characterized with BCA protein assay, DLS, FE-SEM, and TEM. The Curc was embedded by mixing it with Exos in a 1:4 ratio. It was found that the Curc stability has improved after loading on Exos compared to the free Curc. Besides, the in vitro studies using LPS-stimulated HIG-82 synovial cells indicated the efficiency of Curc-Exos in enhancing cytotoxicity and apoptosis compared to the free Curc treatment. It was also revealed that Curc-Exos significantly could reduce the expression levels of anti-apoptotic proteins IAP1 and IAP2 and inflammatory mediators including IL-6, TNF-α, MMP1, and PGE2. This preliminary study confirmed the suitability of Curc-Exos in counteracting the proliferation and inflammatory response of rheumatoid arthritis synovial fibroblasts in vitro.

The great potential of zinc oxide nanoparticles (ZnO NPs) for biomedical applications is attributed to their physicochemical properties. In this work, pure and Ag and Ce dual-doped ZnO NPs were synthesized through a facile and green route to examine their cytotoxicity in breast cancer and normal cells. The initial preparation of dual-doped nanoparticles was completed by the usage of taranjabin. The synthesis of Ag and Ce dual-doped ZnO NPs was started with preparing the Ce:Ag ratios of 1:1, 1:2, and 1:4. The cytotoxicity effects of synthesized nanoparticles against breast normal cells (MCF-10A) and breast cancer cells (MDA-MB-231) were examined. The hexagonal structure of synthesized nanoparticles was observed through the results of X-ray diffraction (XRD). Scanning electron microscopy (SEM) images exhibited the spherical shape and smooth surfaces of prepared particles along with the homogeneous distribution of Ag and Ce in ZnO with high-quality lattice fringes without any distortions. According to the cytotoxic results, the effects of Ag/Ce dual-doped ZnO NPs on breast cancer (MDA-MB-231) cells were significantly more than of pure ZnO NPs, while dual-doped and pure nanoparticles remained indifferent towards breast normal (MCF-10A) cells. In addition, we investigated the antimicrobial activity against harmful bacteria.

The most common infection among young women that increases the risk of developing cervical cancer (CC) is human papillomavirus (HPV). In this study, we are going to assess whether HPV16 DNA concentration helps indicate cervical cancer progression ,As well as for age groups and their relationship to cervical cancer.

Present study included 93 adult females suffering from cervical cancer during the period from 2017 to 2020. Molecular detection of HPV was done using amplification of the L2 gene (minor capsid protein).

Present results showed that 60 (65%) of the patients from 93 cervical cancer cases were infected by HPV16 while only 5 (8%) of healthy patients from the control group were positive for HPV16. So, the current study revealed high HPV16 load in cervical cancer ranged from 1.09 × 10² IU/ml to 5.07 × 10³ IU/ml with a mean ± SD of viral load was 1043.25 ± 8.50 IU/ml while in healthy individuals very low viral load ranging from 88 IU/ml to 101 IU/ml and mean ± SD of viral load was 91.25 ± 2.90 IU/ml was reported.

HPV16 viral load is significantly associated with cervical carcinoma among women in Dhi-Qar Province.

Hyperthermia is an additional treatment method to radiation therapy/chemotherapy, which increases the survival rate of patients without side effects. Nowadays, Auroshell nanoparticles have attracted much attention due to their precise control over heat use for medical purposes. In this research, iron/gold Auroshell nanoparticles were synthesised using green nanotechnology approach. Auroshell gold@hematite nanoparticles were synthesised and characterised with rosemary extract in one step and the green synthesised nanoparticles were characterised by X-ray powder diffraction, SEM, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy analysis. Cytotoxicity of Auroshell iron@gold nanoparticles against normal HUVEC cells and glioblastoma cancer cells was evaluated by 2,5-diphenyl-2H-tetrazolium bromide method, water bath hyperthermia, and combined method of water bath hyperthermia and nano-therapy. Auroshell gold@hematite nanoparticles with minimal toxicity are safe against normal cells. The gold shell around the magnetic core of magnetite caused the environmental and cellular biocompatibility of these Auroshell nanoparticles. These magnetic nanoparticles with targeted control and transfer to the tumour tissue led to uniform heating of malignant tumours as the most efficient therapeutic agent.

Neurodegenerative diseases (NDDs) are conditions that cause neuron structure and/or function to deteriorate over time. Genetic alterations may be responsible for several NDDs. However, a multitude of physiological systems can trigger neurodegeneration. Several NDDs, such as Huntington's, Parkinson's, and Alzheimer's, are assigned to oxidative stress (OS). Low concentrations of reactive oxygen and nitrogen species are crucial for maintaining normal brain activities, as their increasing concentrations can promote neural apoptosis. OS-mediated neurodegeneration has been linked to several factors, including notable dysfunction of mitochondria, excitotoxicity, and Ca2+ stress. However, synthetic drugs are commonly utilized to treat most NDDs, and these treatments have been known to have side effects during treatment. According to providing empirical evidence, studies have discovered many occurring natural components in plants used to treat NDDs. Polyphenols are often safer and have lesser side effects. As, epigallocatechin-3-gallate, resveratrol, curcumin, quercetin, celastrol, berberine, genistein, and luteolin have p-values less than 0.05, so they are typically considered to be statistically significant. These polyphenols could be a choice of interest as therapeutics for NDDs. This review highlighted to discusses the putative effectiveness of polyphenols against the most prevalent NDDs.

Extracellular vesicles (EVs) produced by various immune cells, including B and T cells, macrophages, dendritic cells (DCs), natural killer (NK) cells, and mast cells, mediate intercellular communication and have attracted much attention owing to the novel delivery system of molecules in vivo. DCs are among the most active exosome-secreting cells of the immune system. EVs produced by cancer cells contain cancer antigens; therefore, the development of vaccine therapy that does not require the identification of cancer antigens using cancer-cell-derived EVs may have significant clinical implications. In this review, we summarise the molecular mechanisms underlying EV-based immune responses and their therapeutic effects on tumour vaccination.

The immunotherapeutic approaches based on checkpoint inhibitors, tumor vaccination, immune cell-based therapy, and cytokines were developed to engage the patient's immune system against cancer and better survival of them. While potent, however, preclinical and clinical data have identified that abnormalities in the tumor microenvironment (TME) can affect the efficacy of immunotherapies in some cancers. It is therefore imperative to develop new therapeutic interventions that will enable to overcome tumor-supportive TME and restrain anti-tumor immunity in patients that acquire resistance to current immunotherapies. Therefore, recognition of the essential nature of the tolerogenic TME may lead to a shift from the immune-suppressive TME to an immune-stimulating phenotype. Here, we review the composition of the TME and its effect on tumor immunoediting and then present how targeted monotherapy or combination therapies can be employed for reprogramming educated TME to improve current immunotherapies outcomes or elucidate potential therapeutic targets.

In this research, silver-doped zinc oxide (SdZnO) nanoparticles (NPs) were synthesized in an environmental-friendly manner. The synthesized NPs were identified by UV-vis spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Finally, the antimicrobial activity of synthesized ZnO and SdZnO NPs was performed. It was observed that by doping silver, the size of ZnO NPs was changed. By adding silver to ZnO NPs, the antimicrobial effect of ZnO NPs was improved. Antibacterial test against gram-positive bacterium Streptococcus mutants showed that SdZnO NPs with a low density of silver had higher antibacterial activity than ZnO NPs; Therefore, SdZnO NPs can be used as a new antibacterial agent in medical applications.

Intervertebral disc degeneration (IDD) is highly ubiquitous in the aged population and is an essential factor for low back pain and spinal disability. Because of the association between IDD and senescence, we investigated the ability of the anti-aging drug Klotho to inhibit age-dependent advancement of nucleus pulposus cell (NPC) degeneration. The results indicated that 400 pM exogenous Klotho significantly ameliorated extracellular matrix degradation and angiogenesis. Moreover, we demonstrated that the suppression of angiogenesis and extracellular matrix catabolism was related to inhibition of the Ras-related C3 botulinum toxin substrate 1 (Rac1)/PAK1 axis and matrix metalloproteinase 2 protein expression by exogenous Klotho cotreatment with a Rac1 inhibitor, gene overexpression in NPCs, and stimulation of human umbilical vein endothelial cells with conditioned medium from NPCs. The treatment also preserved the NPC phenotype, viability, and matrix content. In conclusion, these results suggest that the new anti-aging drug Klotho is a potential treatment strategy to mitigate IDD, and thus, provides an innovative understanding of the molecular mechanism of IDD. DATA AVAILABILITY: All data supporting the findings of this study are available from the corresponding authors upon reasonable request.

Low back pain (LBP) is one of the most common musculoskeletal symptoms and severely affects patient quality of life. The majority of people may suffer from LBP during their life-span, which leading to huge economic burdens to family and society. According to the series of the previous studies, intervertebral disc degeneration (IDD) is considered as the major contributor resulting in LBP. Furthermore, non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate diverse cellular processes, which have been found to play pivotal roles in the development of IDD. However, the potential mechanisms of action for ncRNAs in the processes of IDD are still completely unrevealed. Therefore, it is challenging to consider ncRNAs to be used as the potential therapeutic targets for IDD. In this paper, we reviewed the current research progress and findings on ncRNAs in IDD: i). ncRNAs mainly participate in the process of IDD through regulating apoptosis of nucleus pulposus (NP) cells, metabolism of extracellular matrix (ECM) and inflammatory response; ii). the roles of miRNAs/lncRNAs/circRNAs are cross-talk in IDD development, which is similar to the network and can modulate each other; iii). ncRNAs have been attempted to combat the degenerative processes and may be promising as an efficient bio-therapeutic strategy in the future. Hence, this review systematically summarizes the principal pathomechanisms of IDD and shed light on the therapeutic potentials of ncRNAs in IDD.