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An abstract of the article "Effects of Methanol Extract of Soy on the Apoptosis of Hippocampal Cells in Ovariectomized Rats" by Nasirzadeh and colleagues is presented.

Introduction: Nephrotoxicity is an important side-effect of treatment with Methotrexate (MTX). Pentoxifylline (PTX) is an anti-inflammatory and anti-oxidant agent. We hypothesized that pentoxifylline may affords renal protection by downregulating TNF-α as well as by improving cellular anti-oxidant activity. Materials and Methods: Forty five male Wistar rats were assigned to 3 groups of 15 animals each: Group 1: control group (0.9% saline). Group 2: MTX; injected with 20 mg/kg MTX intraperitoneally (i.p.). Group 3: MTX+PTX injected i.p. MTX (20 mg/kg) + PTX (50 mg/kg) i.p. PTX was administered since 3 days before MTX administration and continued for 6 days. After 6 days rats were anesthetized and serum sampled and renal tissue removed for biochemical and histological evaluation. Results: Data showed that glutathione peroxidase (GPx), superoxide dismutase (SOD) activities were lower in PTX+MTX group comparing to MTX group significantly (p<0.05). Renal tissue injury index and percent of TUNEL positive cells, renal tissue malondialdehyde (MDA) levels, serum BUN (Blood Urea Nitrogen), creatinine (Cr) and TNF-α levels were higher in MTX group comparing to MTX+PTX group significantly (p<0.05). Conclusions: In this study, the increased level of tissue MDA and serum TNF-alpha; level together may be suggested that the underlying mechanism is related to direct toxicity of MTX rather than blockage in folate synthesis in kidneys. PTX administration also attenuated renal tissue injury and number of apoptic cells and suppressed the elevation of BUN and Cr levels. However, further studies are essential to elucidate the exact mechanisms of MTX-induced renal toxicity, and protection and the effect of PTX. [ABSTRACT FROM AUTHOR]

Introduction: Despite the known benefits of omega-3 fatty acids on health, there is little knowledge of its effect on fertility. Omega-3 fatty acids can modify gene and protein expression through altering the function of transcription factors controlling gene expression. Cumulus expansion, is a critical process for normal oocyte development, ovulation, and fertilization, this event needs to the synthesis of Progesterone receptors. The aim of this study was to determine if Omega-3 can affect on the expression of PGR in Cumulus cells. Materials and Methods: 30 female mice were kept in standard condition. Female mice were super ovulated with 10 unit hMG and 48 hours later 10 unit HCG as IP injection, for the collection of cumulus- oocyte complexes (COCs) mice were killed 36 hours later by cervical dislocation and COCs were collected from 6-8 weeks old bulb/c female mice oviduct by flashing method. COCs were cultured in 20cc universal medium supplemented with 20 omega-3 and overlaid with mineral oil and incubated for 4-6 hrs at 5% CO2 and 37°C. Surrounding cumulus cells were removed mechanically by using 20 hyaluronidase. The cumulus cells was stored at- 80°C until real-time PCR. PCR was performed by using a master mix containing CYBR green. The expansion level of mRNA PGR was evaluated by real-time PCR. Results: The result showed that the level of expansion of PGR in experimental group comparing with control was significantly increased. Conclusion: The result indicates that omega-3 could improve Cumulus expansion through increasing the amount of expansion of PGR. [ABSTRACT FROM AUTHOR]

Introduction: Formation of oocyte or follicular nests is an early stage of follicular development that is not hormone dependent. Mechanisms regulating the development of primordial follicles and their transition to primary follicles are not well established. The aim of this study is to investigate if maternal treatment with tamoxifen has any effect on fetal follicular differentiation and development. Materials/Methods: This is an experimental work, in which 30 adult female and 15 adult male mice are used. The female mice are divided into two groups of control and experimental. Two female mice at their oestrous cycle were put with one male mouse in a cage for mating. Observation of vaginal plaque was considered as the first day of pregnancy and the mice on day 13 of pregnancy received 100 µg tamoxifen as an ip injection. After delivery, 2-, 3-, 6- and 7-day-old newborns were killed and their ovaries were fixed and prepared for light microscope studies. In the sections, the number of follicular nests, primordial and primary follicles were counted and compared with control values using t test. Results: Microscopy and morphometry revealed that on days 2 and 3, the follicular nests appeared as clusters of somatic or pre-granulosa cells surrounding the oocytes. The number of follicular nests was significantly (P < 0.001) reduced in the experimental group in comparison to the control group (20 ± 1.49 versus 28.8 ± 1.25). In the 6- and 7-day-old infants, the number of follicles was also significantly (P < 0.01) lower than those in the control group 50.85 ± 3.07 versus 62.88 ± 3.33. Conclusion: It is concluded that tamoxifen suppresses follicular differentiation and development at the early stages of folliculogenesis. [ABSTRACT FROM AUTHOR]

Introduction: GSH is the main intracellular antioxidant and its level is important for protecting cell from oxidafive stress. BSO inhibits GSH synthesis and cause oxidative stress. The study is designed to investigate the effect of BSO induced oxidative stress on testicular histology, semen parameters and sperm fertility. Materials and Methods: The adult male mice were divided into two groups of control and experiment. In the experimental group the mice received 2mmol /kg BSO for 35 days as IP injection. All mice were sacrificed at the end of the study and their testes were prepared for histological studies. For determination of semen parameters, sperms were collected from cauda epididymis and analyzed under light microscope. For evaluation of fertility the oocytes were obtained from superovulated mice by tubal flashing and inseminated with sperms. Embryo formation was considered as fertility success and compared in between groups. Results: Semen Analysis revealed that in experimental group the percent of sperms with progressive motility was less than the control group and the percent of sperms with abnormal morphology was higher than in control group (p<0.05). Histomorphometric studies showed that the percent of Tubal Differentiation Index (TDI) and spermatogenic Index (SI) in experimental group were reduced (p<0.01). Microscopic studies revealed that experimental group had undergone vacuolar degeneration and nuclear condensation of spermatogenic cells. Sperm fertility, based on embryo formation, was decreased in experimental group. Conclusion: A morphological change of mice testes in Bso-induced oxidafive stress is accompanied by decreasing of TDI and SI values and fertility rate. [ABSTRACT FROM AUTHOR]

Objective. The aim of the present study was to evaluate the effect of electromagnetic field (EMF) exposure during developmental period on parameters of oxidative stress and histopathology of testis and testosterone level in adult rat F1 generation. Methods and study design. In treatment group pregnant rats were exposed to 3mT EMF, 50Hz for 21 days. The sham group contained pregnant rats under same condition, but out off the EM field. Pregnant rats in room were used as control group. After delivery, the blood samples of mothers for biochemical analyses of total antioxydant capacity (TAC) and malondialdehide (MDA) were provided. The male pups were kept until maturity, then their TAC, MDA and testosterone levels were analyzed, also their tests were removed for investigation of histopathology changes with light microscopy. Results. Biochemical analysis showed that TAC and MDA was significantly increased in pregnant rats in the treatment group when compared with the control group (p<0.05). In adult male of F1 generation MDA was significantly increased in treatment group, but TAC and the testosterone level was significantly decreased in the treatment group as compared with the control group (p<0.05). Microscopic results revealed that in experimental group seminiferous epithelium contained many small irregular empty spaces as the sign of cellular sloughing, spermatogenic cells appeared to be disrupted. The nuclei of spermatogonia cells were heterochromatic, also dense of germinal epithelium and the number of spermatozoa was decreased. Conclusion. The results of this study suggest that pregnant rats exposure in EMF led to oxidative stress in adult male of F1 generation and showed adverse effect on testosterone and spermatogenesis in adulthood which may produce subfertility. [ABSTRACT FROM AUTHOR]

Introduction: Male factors, mainly spermatogenesis disorder, are responsible for 20-30% of infertility occurs in different societies. One of the known causes of spermatogenesis disorder is chemotherapy in patients with cancer. Anticancer drugs affect all of the actively dividing cells in the body including spermatogenic germ cells and thus induces oligospermia or azospermia. These side effects of chemotherapic agents may last from 10 years up to the end of the life. Aim: The aim of the present study is to investigate the preventive effect of GnRH antagonist, as a suppressor of spermatogonial proliferation, on spermatogenesis disorder produced by an anticancer drug. Methods: In the present study 45 adult male mice aging 6-8 weeks were used. The mice were divided into 3 equal groups as; control, experimental-1 receiving thiotepa and experimental-2 receiving thiotepa + GnRH antagonist (cetrorelix). Thiotepa was injected as ip for 5 days at 2.5 mg/kg doses. In experimental 2 group, cetrorelix was injected along with thiotepa treatment. Since spermatogenic cycle in mice is 35 days, mice in all groups were sacrificed 35 days after thiotepa injection. Half of the testicular specimens were fixed in 10% formaldehyde for histological and histochemical studies (proliferation and apoptosis). Proliferation was assessed by Ki-67 kit and apoptosis determined by TUNEL technique. The other half of the specimens were fixed in 2% glutaraldehyde and prepared for EM studies. The thin sections were studied with LEO 906 TEM. Results: Electron microscopic study showed the presence of apoptotic features as apoptotic bodies in spermatogonia and leydig cells and pre-apoptotic features as nuclear condensation and vacuolization in sertoli cells. The apoptotic features were frequent in experimental-1 group, the group that received thiotepa, but rare in control and experimental-2 groups. Comparison of the result of the histochemical studies showed that the mean number of proliferative cells in control group were 10.01±0.29, in experimental-1 group were 4.58±0.55 and in experimental-2 group were 9.35±0.73. Statistical analysis of the data showed a significant difference between control and experimental-1 group (P < 0.05) but not between control and experimental-2 group (P > 0.05). Conclusion: According to the results it is concluded that administration of GnRH antagonist, along with cancer treatment, could prevent the detrimental effect of anticancer drugs on spermatogenesis. [ABSTRACT FROM AUTHOR]

Purpose: We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors in vitro ., Methods: PAMAM G5 dendrimers were crosslinked with a hypoxic azo linker, attached to a mPEG to form a detachable corona on the dendrimer surface (PAP NPs). NPs were characterized by Zeta sizer, transmission electron microscope (TEM), Fourier transforms infrared (FTIR) and drug release kinetics. The anti-cancer performance of PAPs was evaluated by numerous tests in 2D and 3D cultured MDA-MB-231 breast cancer cells., Results: MTT assay showed a significant difference between PAP and PAMAMG5 in terms of biocompatibility, and the effect of PAP@DOX was significantly greater than free DOX in hypoxic conditions. The results of DAPI and Annexin V-FITC/PI cell staining also confirmed uniform drug penetration as validated by induction of 90% cell apoptosis in spheroids and a high level of PAP@DOX-induced ROS generation under hypoxia conditions. Mechanistically, PAP@DOX significantly reduced the expression of mTOR, and Notch1, while the expression of Bax and Caspase3 was considerably unregulated, compared to the controls. Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells., Conclusion: Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors., Competing Interests: None to declare., (©2024 The Author (s).)

There is presently no disease-modifying therapy for Alzheimer's Disease (AD), which is the most prevalent cause of dementia., Objective: This study aspires to estimate the efficacy and safety of cell-based treatments in AD., Methods: Observing the Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search was accomplished in PubMed, Medical Literature Analysis and Retrieval System Online (Medline, via Ovid), Embase; Cochrane, and Cumulative Index of Nursing and Allied Health Literature - CINAHL (via EBSCO) databases up to June 2023. The relevant clinical studies in which cell-based therapies were utilized to manage AD were included. The risk of bias was evaluated using the JBI checklists, based on the study designs., Results: Out of 1,014 screened records, a total of five studies with 70 individuals (including 59 patients receiving stem cells and 11 placebo controls) were included. In all these studies, despite the discrepancy in the origin of stem cells, cell density, and transplant site, safety goals were obtained. The intracerebroventricular injection of adipose-derived stromal vascular fraction (ADSVF) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), the intravenous injection of Lomecel-B, and the bilateral hippocampi and right precuneus injection of UC-MSCs are not linked to any significant safety concerns, according to the five included studies. Studies also revealed improvements in biomarkers and clinical outcomes as a secondary outcome. Three studies had no control groups and there are concerns regarding the similarity of the groups in others. Also, there is considerable risk of bias regarding the outcome assessment scales., Conclusion: Cell-based therapies are well tolerated by AD patients, which emphasizes the need for further, carefully planned randomized studies to reach evidence-based clinical recommendations in this respect., Competing Interests: Disclosure: The authors report no conflicts of interest.

Neurological disorders are a diverse group of conditions that can significantly impact individuals' quality of life. The maintenance of neural microenvironment homeostasis is essential for optimal physiological cellular processes. Perturbations in this delicate balance underlie various pathological manifestations observed across various neurological disorders. Current treatments for neurological disorders face substantial challenges, primarily due to the formidable blood-brain barrier and the intricate nature of neural tissue structures. These obstacles have resulted in a paucity of effective therapies and inefficiencies in patient care. Exosomes, nanoscale vesicles that contain a complex repertoire of biomolecules, are identifiable in various bodily fluids. They hold substantial promise in numerous therapeutic interventions due to their unique attributes, including targeted drug delivery mechanisms and the ability to cross the BBB, thereby enhancing their therapeutic potential. In this review, we investigate the therapeutic potential of exosomes across a range of neurological disorders, including neurodegenerative disorders, traumatic brain injury, peripheral nerve injury, brain tumors, and stroke. Through both in vitro and in vivo studies, our findings underscore the beneficial influence of exosomes in enhancing the neural microenvironment following neurological diseases, offering promise for improved neural recovery and management in these conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To examine the potential of intra-articular administration of mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue to mitigate synovial inflammation in a rat model of temporomandibular joint (TMJ) osteoarthritis (OA)., Methods: In this experimental study, 40 rats were divided into 4 groups: (1) Control group; (2) Untreated TMJ-OA group; (3) TMJ-OA group treated with bone marrow-derived MSCs; (4) TMJ-OA group treated with adipose tissue-derived MSCs. The TMJ-OA model was established by inducing synovial inflammation through the intra-articular administration of complete Freund's adjuvant (CFA). After 8 weeks of TMJ-OA establishment, the animals were sacrificed and each mandibular condyle was extracted for histological evaluation., Results: The untreated TMJ-OA group had significantly higher synovial inflammation, as indicated microscopically by higher grades of synovial membrane hyperplasia and adhesion, vascular vasodilation, and fibrin deposition than the control group (p < 0.001). Both TMJ-OA groups treated with MSCs had lower grades of synovial inflammation and less severe synovitis than the untreated TMJ-OA group (p < 0.001). The TMJ-OA group treated with adipose tissue-derived MSCs showed lower grades of synovial membrane hyperplasia and higher grades of fibrin deposition than the that treated with bone marrow-derived MSCs (p < 0.001). Other indicators of synovial inflammation and synovitis severity were comparable between the two treatment groups., Conclusions: Administration of CFA to the TMJ-OA rat model augmented synovial inflammation. Intra-articular administration of MSCs derived from either bone marrow or adipose tissue attenuated the microscopic manifestations of this inflammation, indicating the therapeutic potential of this treatment for TMJ-OA., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024. Published by Elsevier B.V.)

The study examines the induction of apoptosis in colon cancer stem cells (CCSCs) within a 3D culture setting, employing an innovative cold atmospheric plasma (CAP) transmission method known as two-stage transferred cold atmospheric plasma (TS-TCAP). TS-TCAP is a partially or fully ionized non-thermal gaseous mixture that comprises photons, charged and neutral particles, and free radicals, which has gained traction in biomedical applications such as cancer therapy. TS-TCAP impacts CCSCs via a continuous, two-step transport process, facilitating the efficient delivery of reactive oxygen and nitrogen species (RONS). The key cellular factors of CCSCs impacted by TS-TCAP treatment, encompassing the secretion and expression levels of IL-6 and IL-8, apoptotic cell count, and expression of BAX, BCL-2, and KI-67 proteins, were evaluated using qrt-ELISA, Annexin V, and qrt-PCR procedures, respectively. The outcomes of CCSCs treatment with TS-TCAP reveal a notable rise in the number of apoptotic cells ( P <0.0001), diminished secretion, and gene expression of IL-6 and IL-8 ( P <0.0001), accompanied by favorable alterations in BCL-2 and BAX gene expression ( P <0.0001). Additionally, a notable decrease in KI-67 expression was observed, correlating with a reduction in CCSCs proliferation ( P <0.0001). As well, this study underscores the anti-cancer potential of TS-TCAP, showcasing its efficacy in reducing CCSCs survival rates. However, further pre-clinical and clinical trials are necessary to evaluate CAP's efficacy, safety, and potential synergistic effects with other therapies thoroughly. Overall, TS-TCAP presents a promising alternative for CCSCs treatment, pending further investigation and refinement., Competing Interests: The authors declare no conflict of interest., (©2024 The Authors.)

Background: To investigate the effect of plasma-derived extracellular vesicles (EVs) or conventional medium in fertilization and early embryo development rate in mice., Methods and Results: MII oocytes (matured in vivo or in vitro conditions) were obtained from female mice. The extracellular vesicles were isolated by ultracentrifugation of plasma and were analyzed and measured for size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM). By western blotting analysis, the EVs proteins markers such as CD82 protein and heat shock protein 90 (HSP90) were investigated. Incorporating DiI-labeled EVs within the oocyte cytoplasm was visible at 23 h in oocyte cytoplasm. Also, the effective proteins in the early reproductive process were determined in isolated EVs by western blotting. These EVs had a positive effect on the fertilization rate (P < 0.05). The early embryo development (8 cell, morula and blastocyst stages) was higher in groups supplemented with EVs (P < 0.01)., Conclusion: Our findings showed that supplementing in vitro maturation media with EVs derived- plasma was beneficial for mice's embryo development., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study., Methods and Results: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002)., Conclusions: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit + cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit + cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit + cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000 C-kit + cells, and (4) Diabetic + C-kit - cells (D + C-kit neg), intravenously injected C-kit - cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit + cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit + group compared to the diabetic group. These findings suggest that C-kit + cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stem cell-based therapy has been proposed as a novel therapeutic strategy for diabetic nephropathy. This study was designed to evaluate the effect of systemic administration of rat bone marrow-derived c-kit positive (c-kit + ) cells on diabetic nephropathy in male rats, focusing on PI3K/AKT/GSK-3β pathway and apoptosis as a possible therapeutic mechanism. Twenty-eight animals were randomly classified into four groups: Control group (C), diabetic group (D), diabetic group, intravenously received 50 μl phosphate-buffered saline (PBS) containing 3 × 10 5  c-kit - cells (D + ckit - ); and diabetic group, intravenously received 50 μl PBS containing 3 × 10 5 c-Kit positive cells (D + ckit + ). Control and diabetic groups intravenously received 50 μl PBS. C-kit + cell therapy could reduce renal fibrosis, which was associated with attenuation of inflammation as indicated by decreased TNF-α and IL-6 levels in the kidney tissue. In addition, c-kit + cells restored the expression levels of PI3K, pAKT, and GSK-3β proteins. Furthermore, renal apoptosis was decreased following c-kit + cell therapy, evidenced by the lower apoptotic index in parallel with the increased Bcl-2 and decreased Bax and Caspase-3 levels. Our results showed that in contrast to c-kit - cells, the administration of c-kit + cells ameliorate diabetic nephropathy and suggested that c-kit + cells could be an alternative cell source for attenuating diabetic nephropathy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Burn wounds are the most destructive and complicated type of skin or underlying soft tissue injury that are exacerbated by a prolonged inflammatory response. Several cell-based therapeutic systems through the culturing of potent stem cells on modified scaffolds have been developed to direct the burn healing challenges. In this context, a new regenerative platform based on boron (B) enriched-acellular sheep small intestine submucosa (AOSIS) scaffold was designed and used as a carrier for mesenchymal stem cells derived from Wharton's jelly (WJMSCs) aiming to promote the tissue healing in burn-induced rat models. hWJMSCs have been extracted from human extra-embryonic umbilical cord tissue. Thereafter, 96 third-degree burned Wistar male rats were divided into 4 groups. The animals that did not receive any treatment were considered as group A (control). Then, group B was treated just by AOSIS scaffold, group C was received cell-seeded AOSIS scaffold (hWJMSCs-AOSIS), and group D was covered by boron enriched-cell-AOSIS scaffold (B/hWJMSCs-AOSIS). Inflammatory factors, histopathological parameters, and the expression levels of epitheliogenic and angiogenic proteins were assessed on 5, 14 and 21 d post-wounding. Application of the B/hWJMSCs-AOSIS on full-thickness skin-burned wounds significantly reduced the volume of neutrophils and lymphocytes at day 21 post-burning, whilst the number of fibroblasts and blood vessels enhanced at this time. In addition, molecular and histological analysis of wounds over time further verified that the addition of boron promoted wound healing, with decreased inflammatory factors, stimulated vascularization, accelerated re-epithelialization, and enhanced expression levels of epitheliogenic genes. In addition, the boron incorporation amplified wound closure via increasing collagen deposition and fibroblast volume and activity. Therefore, this newly fabricated hWJMSCs/B-loaded scaffold can be used as a promising system to accelerate burn wound reconstruction through inflammatory regulation and angiogenesis stimulation., (© 2024 IOP Publishing Ltd.)

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is a major reproductive endocrine disorder affecting different facets of a woman's life, comprising reproduction, metabolism, and mental health. Recently, several research groups have brought attention to the therapeutic capacity of mesenchymal stem cells (MSCs) for the treatment of female reproductive disorders. It is highlighted that the treatment with bone marrow mesenchymal stem cells (BMMSCs) considerably diminishes the levels of some inflammatory markers as well as essential genes for ovarian production of androgens, which are considerably higher in theca cells of PCOS women than in those of healthy cases. In addition, studies show that BMMSCs improve in vitro maturation (IVM) of germinal vesicles (GVs) and the number of antral follicles while lessening the number of primary and preantral follicles in mice with PCOS compared to healthy controls. Regarding adipose- derived mesenchymal stem cells (AdMSCs), these cells restore the ovarian structure, enhance the number of oocytes and corpora luteum, and diminish the number of aberrant cystic follicles in PCOS rats. Some research also indicates that umbilical cord mesenchymal stem cells (UC-MSCs) alleviate the inflammation of granulosa cells in women with PCOS. Therefore, due to the limited research on MSC therapy in PCOS, in this review, we summarize the current knowledge on the therapeutic potential of three types of MSCs: BMMSCs, AdMSCs, UC-MSCs and their secretome in the treatment of PCOS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Recently, the demand for organ transplantation has promptly increased due to the enhanced incidence of body organ failure, the increasing efficiency of transplantation, and the improvement in post-transplant outcomes. However, due to a lack of suitable organs for transplantation to fulfill current demand, significant organ shortage problems have emerged. Developing efficient technologies in combination with tissue engineering (TE) has opened new ways of producing engineered tissue substitutes. The use of natural nanoparticles (NPs) such as nanocellulose (NC) and nano-lignin should be used as suitable candidates in TE due to their desirable properties. Many studies have used these components to form scaffolds and three-dimensional (3D) cultures of cells derived from different tissues for tissue repair. Interestingly, these natural NPs can afford scaffolds a degree of control over their characteristics, such as modifying their mechanical strength and distributing bioactive compounds in a controlled manner. These bionanomaterials are produced from various sources and are highly compatible with human-derived cells as they are derived from natural components. In this review, we discuss some new studies in this field. This review summarizes the scaffolds based on NC, counting nanocrystalline cellulose and nanofibrillated cellulose. Also, the efficient approaches that can extract cellulose with high purity and increased safety are discussed. We concentrate on the most recent research on the use of NC-based scaffolds for the restoration, enhancement, or replacement of injured organs and tissues, such as cartilage, skin, arteries, brain, and bone. Finally, we suggest the experiments and promises of NC-based TE scaffolds., Competing Interests: Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Purpose: Exosomes are natural nanoparticles that participate in intercellular communication through molecular transport. Recently, due to their membrane vesicular structure and surface proteins, exosomes have been used extensively in the research field of drug delivery. Osteoporosis is an inflammation in which the cellular balance of bone tissue is disturbed that reduces bone density and making bone prone to abnormal fractures with small amount of force. Utilizing estrogen is one of the main therapeutic strategies for osteoporosis. Despite the positive effects of estrogen on bone tissue, changes in the natural estrogen levels of the body can cause a number of diseases such as different types of cancer. Therefore, designing a therapeutic system which controls more accurate tissue targeting of estrogen seems to be a rational and promising practical approach., Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes were loaded by estradiol using two different methods of drug loading, namely incubation and sonication methods and then the survival effects of the drug loaded exosomes on BMMSCs was investigated., Results: Examination of size, shape, and surface factors of exosomes in different states (pure exosomes and drug-loaded exosomes) showed that the round morphology of exosomes was preserved in all conditions. However, the particles size increased significantly when loaded by sonication method. The increased survival of BMMSCs was noted with estradiol-loaded exosomes when compared to the control group., Conclusion: The results suggest that estradiol-loaded exosomes have potential to be used as nano-drug carriers in the treatment of osteoporosis., Competing Interests: The authors declare that they have no conflict of interest., (©2023 The Authors.)

Skeletal problems are an increasing issue due to the increase in the global aging population. Different statistics reports show that today, the global population is aging that results in skeletal problems, increased health system costs, and even higher mortality associated with skeletal problems. Common treatments such as surgery and bone grafts are not always effective and in some cases, they can even cause secondary problems such as infections or improper repair. Cell therapy is a method that can be utilized along with common treatments independently. Mesenchymal stem cells (MSCs) are a very important and efficient source in terms of different diseases, especially bone problems. These cells are present in different tissues such as bone marrow, adipose tissue, umbilical cord, placenta, dental pulp, peripheral blood, amniotic fluid and others. Among the types of MSCs, bone marrow mesenchymal stem cells (BMMSCs) are the most widely used source of these cells, which have appeared to be very effective and promising in terms of skeletal diseases, especially compared to the other sources of MSCs. This study focuses on the specific potential and content of BMMSCs from which the specific capacity of these cells originates, and compares their osteogenic potential with other types of MSCs, and also the future directions in the application of BMMSCs as a source for cell therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)