A systematic review of clinical efficacy and safety of cell-based therapies in Alzheimer's disease.

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.

Atualmente, não há terapia modificadora da doença para a doença de Alzheimer (DA), que é a causa mais prevalente de demência. Objetivo: Este estudo teve como objetivo estimar a eficácia e segurança dos tratamentos baseados em células na DA. Métodos: Observando os métodos do JBI e a declaração PRISMA, uma busca sistemática foi realizada nas bases de dados PubMed, Medical Literature Analysis and Retrieval System Online ­ Medline (via Ovid), Embase, Cochrane e CINAHL (via EBSCO) até junho de 2023. Foram incluídos os estudos clínicos relevantes nos quais terapias baseadas em células foram utilizadas para gerenciar a DA. O risco de viés foi avaliado utilizando os checklists do JBI, com base nos desenhos dos estudos. Resultados: Dos 1.014 registros examinados, foi incluído um total de cinco estudos com 70 indivíduos (incluindo 59 pacientes que receberam células-tronco e 11 controles de placebo). Em todos esses estudos, apesar da discrepância na origem das células-tronco, densidade celular e local de transplante, os objetivos de segurança foram alcançados. A injeção intracerebroventricular de ADSVF e UC-MSCs, a injeção intravenosa de Lomecel-B e a injeção bilateral dos hipocampos e precuneus direito de UC-MSCs não estão relacionadas a quaisquer preocupações significativas de segurança, de acordo com os cinco estudos incluídos. Os estudos também revelaram melhorias nos biomarcadores e resultados clínicos como um desfecho secundário. Três estudos não tinham grupos de controle e há preocupações quanto à semelhança dos grupos em outros. Além disso, há um risco considerável de viés em relação às escalas de avaliação de desfechos. Conclusão: As terapias baseadas em células são bem toleradas por pacientes com DA, o que enfatiza a necessidade de mais estudos randomizados cuidadosamente planejados para alcançar recomendações clínicas baseadas em evidências.

A Two-Stage Transferred Cold Atmospheric Plasma as a Unique Therapeutic Strategy for Targeting Colon Cancer Stem Cells.

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.

Therapeutic Effects of Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue in a Rat Model of Temporomandibular Osteoarthritis.

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.

Beyond boundaries: The therapeutic potential of exosomes in neural microenvironments in neurological disorders.

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.

The effectiveness of ruxolitinib and cyclophosphamide combination on T helper 17 and regulatory T cells in rat experimental membranous glomerulonephritis.

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.

Plasma-derived extracellular vesicles improve mice embryo development.

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.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

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.

Bone Marrow-Derived C-Kit+ Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats.

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.

The effect of Wharton's jelly-derived stem cells seeded/boron-loaded acellular scaffolds on the healing of full-thickness burn wounds in the rat model.

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.

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

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.

Bone marrow-derived c-kit positive stem cell administration protects against diabetes-induced nephropathy in a rat model by reversing PI3K/AKT/GSK-3ß pathway and inhibiting cell apoptosis.

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-3ß 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 × 105 c-kit- cells (D + ckit-); and diabetic group, intravenously received 50 µl PBS containing 3 × 105 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-3ß 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.

17ß-Estradiol-Loaded Exosomes for Targeted Drug Delivery in Osteoporosis: A Comparative Study of Two Loading Methods.

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.

An overview to nanocellulose clinical application: Biocompatibility and opportunities in disease treatment.

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.

The Effect of Low-Frequency Pulsed Electromagnetic Fields on the Differentiation of Permanent Dental Pulp Stem Cells into Odontoblasts.

Introduction: Exposure to pulsed electromagnetic field (PEMF) has been revealed to affect the differentiation and proliferation of human mesenchymal stem cells derived from dental pulp multipotent stromal stem cells (DP-MSCs). This study aimed to investigate the differentiation effect of electromagnetic fields (EMFs) on the DP-MSC. Materials and Methods: PEMF was produced by a system comprising a multi-meter autotransformer, solenoid coils, and teslameter. This study included 10 groups of DP-MSCs which underwent different electromagnetic radiation time and beam intensity. Three samples tested for each group. The effect of PEMF with the intensity of 0.5 and 1 mT (mili Tesla) and 50 Hz on the proliferation rate of DP-MSC was evaluated at 20 and 40 minutes per day for seven days. MTT assay was applied to determine the growth and proliferation of DP-MSC. Gene expression of DMP1 for differentiation of DPSCs to odontoblasts was confirmed by Real Time PCR., ANOVA statistical analysis and Kruskal-Wallis test were used to analyze the data. Results: The survival in all exposure groups was significantly higher than that in control except in the group of 40 minutes, 1 mT (P<0.05). In 20 minutes, 0.5 mT exposure, the survival intensity is significantly more than others (P<0.05). In general, the intensity of survival was recorded, 20, 0.5 mT≥20, 1 mT≥40, 0.5 mT≥40, 1 mT respectively. Therefore, according to the obtained results, ELF-EMF increases the survival of cells except for one case (40 minutes, 1 mT), even though the effective underlying mechanisms in this process are still unclear. Conclusions: The results obtained promise that in the future, by placing an important part of the pulp next to the electromagnetic field, the lost part of the pulp can be reconstructed and the dentin barrier can be created.

Alleviative Effects of Adipose Tissue-derived Stem Cells and α-NETA on Metabolic, Biochemical, and Endocrine Parameters in a Letrozole-induced Rat Model of PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS), the most prevalent reproductive disorder, is accompanied by hyperandrogenism (HA), ovulatory dysfunction (OD), and insulin resistance (IR). A number of reports indicate that adipokines play a vital role in the pathophysiology of PCOS. One of these adipokines is chemerin, which is engaged in metabolic disorders, especially obesity, diabetes, and PCOS. Based on the data, the circulating levels of chemerin and the expression of chemokine-like receptor-1 (CMKLR1) in white adipose tissue (WAT) of women with PCOS are significantly higher than in healthy ones. Currently, several scholars have emphasized the therapeutic capacities of stem cells, notably mesenchymal stem cells (MSCs), for the treatment of PCOS. OBJECTIVE: In this study, for the first time, the impacts of 2-(α-naphthoyl) ethyltrimethylammonium iodide (α- NETA), an antagonist of CMKLR1, adipose-derived stem cells (ADSCs), and their combinations on metabolic and endocrine aberrancies were assessed in the WAT and ovarian tissues of the letrozole (LET)-induced PCOS rats. METHODS: In the current study, 30 Wistar rats were randomly divided into five groups: control (n = 6), LET-induced PCOS (1.5 mg/kg p.o., n = 6), LET + ADSCs (106 ADSCs i.v., n = 6), LET + α-NETA (10 mg/kg p.o., n = 6), and LET + ADSCs + α-NETA (n = 6). The blood samples and adipose and ovarian tissues were obtained to evaluate the effects of ADSCs and α-NETA on hormonal and metabolic parameters in the PCOS rats. RESULTS: Our findings showed that the administration of α-NETA, ADSCs, and the combination of both favorably restored the irregular estrus cycle and considerably modulated the endocrine parameters in PCOS rats. In addition, these therapeutic factors remarkably regulated steroidogenic and adipogenic gene expressions, as well as the genes related to glucose metabolism and brown adipose tissue (BAT) markers in these animals. CONCLUSION: These findings indicate that the combination of ADSCs and α-NETA can successfully ameliorate metabolic and endocrine dysfunction in LET-induced PCOS rats, and this strategy could be a new therapeutic choice for patients with PCOS.

Kaempferol: A Dietary Flavonol in Alleviating Obesity.

Obesity is considered as a chronic and high-prevalence disease on a global scale which affects all genders and ages. Although various drugs have been confirmed for the treatment of obesity, these medications have been shown to have a number of adverse effects on health. It is highlighted that natural products have an alleviative role in a broad spectrum of diseases, in particular obesity, and diabetes. Kaempferol (KMP), a plant- derived flavonol, is considerably engaged in the suppression of oxidative stress, radical scavenging, opposing cellular toxicity, and induction of the production and release of growth factors. This flavonol combats obesity by suppressing adipogenesis, regulating lipid and glucose metabolism, changing gut microbiota, and activating autophagy. Also, studies have shown that KMP exerts its anti-obesity actions by decreasing the accumulation of lipids and triglycerides (TGs), increasing fatty acid oxidation, and regulating multiple metabolic genes in the adipocytes. Considering that KMP may be a potential candidate for combating obesity, this paper summarizes the possible therapeutic roles of KMP in the treatment and prevention of this disease.

Effect of autologous conditioned serum (ACS) on histological characteristics and expression of soft tissue IL-1ß gene after horizontal ridge augmentation surgery.

Background: Horizontal ridge augmentation surgeries are common procedures in periodontics. Histological changes in soft tissues affect the success of surgery in many ways. Autologous conditioned serum (ACS) increases interleukin-1 receptor antagonist (IL-1Ra) and causes inflammation modulation. Therefore, the present study aimed to investigate the effect of ACS on histological changes and gene expression of soft tissues after horizontal ridge augmentation surgeries. Methods: This double-blind split-mouth clinical trial was performed on patients needing implants with horizontal ridge augmentation (n=21). The control and intervention groups were considered split-mouth in two areas of the patients' oral soft tissues. A collagen membrane impregnated with ACS was used on the test side, and only a collagen membrane was used on the control side. After four months, histological changes in soft tissues, such as the amount of connective tissue collagen, fibroblast and inflammatory cell counts, and expression of the IL-1ß gene, were evaluated. Results: The fibroblast counts in the ACS group were significantly higher than in the control group. In addition, ACS caused a significant increase in the amount of collagen in the soft tissues compared to the control group (P<0.01). However, the number of inflammatory cells was similar in the two groups (P>0.05). IL-1ß gene expression was not significantly different between the case and control groups. Conclusion: Under the limitations of the present study and based on the results of histological examinations, ACS increased the number of fibroblasts and the amount of collagen in soft tissues without affecting inflammatory cells (P=0.562).

Correction to: Evaluation of the effect of autologous conditioned serum on the radiographic characteristics of hard tissue after horizontal bone augmentation in implant dentistry.

[This corrects the article DOI: 10.34172/japid.2022.015.].

Exosomes from Adipose Tissue-derived Mesenchymal Stem Cells Induce Regulatory T Cells in COVID-19 Patients.

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue-derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-ß1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo-treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-ß was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.