Samaneh Salehipour Bavarsad

Background: Nonalcoholic fatty liver disease and its inflammatory, progressive form, nonalcoholic steatohepatitis (NAFLD/NASH), represent a continuum of metabolic liver pathology characterized by steatosis and hepatic inflammation. Despite its rising global prevalence, effective disease-modifying therapies remain limited. Accumulating evidence indicates that mesenchymal stromal cell-derived exosomes (MSC-Exo) represent a novel and potentially effective cell-free therapeutic option for metabolic liver disorders. Objectives: The current study aimed to comprehensively evaluate the therapeutic efficacy of exosomes isolated from lipopolysaccharide (LPS)-conditioned MSCs in ameliorating NASH induced by a high-fat diet, with a specific focus on modulating the AMPK/ACC signaling pathway. Methods: In this experimental study, male Wistar rats were fed a high-fat diet for eight weeks to induce NASH. Forty rats were allocated into five groups (n = 8/group), including a control group and four HFD-fed groups. From week 8, animals received saroglitazar or exosomes derived from either naïve MSCs or LPS-primed MSCs for six weeks via intravenous (tail vein) injection (150 µg protein). Exosomes were characterized by transmission electron microscopy (TEM), particle size analysis, and Western blotting for CD9 and CD81. Body and liver weight, hepatic triglyceride levels, liver function markers, fibrosis-related genes, and collagen deposition were evaluated. Gene expression analysis of lipid metabolism, inflammation, fibrosis, and AMPK/ACC signaling was performed using qRT-PCR. Results: Treatment with exosomes derived from LPS-primed MSCs significantly attenuated HFD-induced hepatic steatosis, as evidenced by reduced liver weight and hepatic triglyceride accumulation (P < 0.01 - 0.001). These effects were associated with activation of the AMPK/ACC signaling pathway, suppression of lipogenic gene expression, and improved metabolic homeostasis. Furthermore, LPS-primed MSC exosomes significantly improved serum lipid parameters and reduced ALT and AST levels (P < 0.05 - 0.001). A marked reduction in pro-inflammatory mediators and hepatic collagen deposition was also observed compared with untreated and naïve MSC exosome-treated groups. Conclusions: Exosomes derived from LPS-primed MSCs exert significant hepatoprotective and antifibrotic effects in HFD-induced NASH. These beneficial effects are mediated, at least in part, through activation of the AMPK/ACC signaling pathway and suppression of inflammatory and fibrogenic responses. Collectively, these findings suggest that LPS-primed MSC-derived exosomes may represent a promising cell-free therapeutic strategy for the management of NASH.

Background: Hepatocellular carcinoma (HCC) is the most prevalent type of liver malignancy worldwide. Traditional cancer treatments, such as chemotherapy and radiotherapy, often pose significant risks, including potential organ damage and, in severe cases, death. Etoposide (ETO), a commonly used chemotherapeutic agent, is not exempt from these complications. Combinational therapies have been explored for years as promising strategies to enhance treatment efficacy while mitigating adverse side effects. Stem cell-derived exosomes, recognized for their therapeutic potential, have emerged as valuable tools in cancer treatment due to their anti-cancer properties. Objectives: The present study investigates the potential synergistic effects between stem cell-derived exosomes and ETO in inducing apoptosis in HepG2 HCC cells. Methods: Cell apoptosis was evaluated using Annexin V/PI staining along with caspase-3 and -9 activity assays. Gene expression of Bax and Bcl-2 was measured by qRT-PCR, while p53 protein levels were assessed using western blotting. Results: Treatment with both stem cell-derived exosomes (100 µg/mL) and ETO (10 µM) significantly reduced HepG2 cell viability and induced apoptosis (16.2%) compared to either treatment alone. Caspase-9 and -3 activities increased to 69% and 64%, respectively, under combined treatment, versus 33% and 31% with exosomes and 51% and 39% with ETO alone. Bax expression rose by 3.6-fold, and Bcl-2 decreased to 0.44-fold upon co-treatment, leading to a markedly elevated Bax/Bcl-2 ratio. Moreover, p53 protein levels increased 3.24-fold, highlighting the enhanced apoptotic signaling. These results confirm a synergistic effect between exosomes and ETO. Conclusions: Our findings reveal that stem cell-derived exosomes exhibit synergistic effects when co-treated with ETO in HepG2 cells. Building on these results, we conclude that further investigation of this combination could lead to the development of a promising anti-cancer therapy for HCC.

Background: Hepatic fibrosis is a biological response characterized by the accumulation of extracellular matrix (ECM) during the wound healing process. Hepatic stellate cells (HSCs) play a pivotal role in fibrogenesis, transitioning from quiescent to myofibroblast cell types and leading to excessive ECM production. Platelet-derived growth factor (PDGF), a potent mitogen, is produced by activated HSCs, stimulating cell proliferation and migration. Objectives: This study aims to analyze the impact of Wharton's jelly mesenchymal stem cell (WJ-MSC)-derived exosomes on HSC activation induced by PDGF during liver fibrosis. Methods: Hepatic stellate cells-T6 cells were treated with PDGF-BB for 24 hours to induce activation, followed by treatment with varying concentrations of WJ-MSC-derived exosomes (0, 25, and 50 µg/mL) for another 24 hours. The effects of exosome treatment on HSC activation were evaluated through flow cytometry, differentiation assays, dynamic light scattering (DLS), transmission electron microscopy (TEM), RT-PCR, and western blot analysis. Results: Our study yields promising results, highlighting the potential therapeutic effects of WJ-MSC-derived exosomes on liver fibrosis. The dose-dependent decrease in fibrotic markers such as α-SMA, COLA1, and phosphorylated AKT protein in PDGF-BB-treated HSC-T6 cells suggests that WJ-MSC exosomes exert an anti-fibrotic effect by inhibiting HSC activation. Conclusions: These findings suggest that exosomes derived from WJ-MSCs hold therapeutic promise for liver fibrosis treatment by targeting key pathways involved in HSC activation and fibrogenesis. Further investigation into the underlying mechanisms of this anti-fibrotic effect and the potential clinical applications of WJ-MSC-derived exosomes in liver fibrosis management is warranted.

Background: One of the primary drivers of liver fibrosis is the excessive accumulation of extracellular matrix (ECM), primarily caused by the over-proliferation of hepatic star-shaped cells (HSCs). The activation of HSCs by transforming growth factor beta (TGF-β) has a critical role in initiating fibrosis. Recent studies have suggested that miRNA-133a significantly ...

Background: Human brucellosis is one of the most common zoonosis infections, with a high prevalence in some regions of the world. It is considered one of the vital health and economic problem worldwide. This study aimed to investigate the trend of seroprevalence of brucellosis among Suspected Patients attending a medical center, ...

Background: Hepatic fibrosis is characterized by the increased proliferation and activation of hepatic stellate cells. Transforming growth factor-beta (TGF-β) stimulates these stellate cells, leading to the development of liver fibrosis. MicroRNA-146a and microRNA-29b have been identified as significant regulatory factors in fibrogenesis. Objectives: In this study, we investigated the ability of exosomes to alleviate liver fibrosis by enhancing the antifibrotic effects of miR-146a and miR-29b. Methods: The LX-2 cells were exposed to TGF-β for 24 hours. Subsequently, the cells were treated with exosomes for an additional 24 hours. Following this treatment, the mRNA expression levels of alpha-smooth muscle actin (α-SMA), collagen1α, miR-146a, and miR-29b, as well as the protein levels of phosphorylated Smad3 (p-Smad3), were evaluated. Results: The findings revealed a significant elevation in the expression of α-SMA (5.37-fold, P < 0.0001) and collagen1α (3.87-fold, P < 0.001) genes, as well as an increase in the levels of p-Smad3 protein (5.87-fold, P < 0.0001) in the presence of TGF-β. Moreover, the expression of miR-146a (0.54-fold, P < 0.05) and miR-29b (0.46-fold, P < 0.01) genes exhibited a notable decrease compared to the control group under the influence of TGF-β. In our investigation, the administration of exosomes effectively mitigated the TGF-β-induced up-regulation of α-SMA (3.26-fold, P < 0.01) and collagen1α (1.76-fold, P < 0.01) genes, as well as the p-Smad3 protein (2.86-fold, P < 0.01), in LX-2 cells. Conclusions: Our results suggest that exosomes effectively impede the continuous activation of hepatic stellate cells (HSCs) by enhancing the antifibrotic effects mediated by miR-146a and miR-29b. Moreover, exosomes demonstrate inhibitory effects on the TGF-β/Smad3 signaling pathway, resulting in decreased extracellular matrix (ECM) accumulation in the context of in vitro liver fibrosis.

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED. On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation. Graphical Abstract

Background: Liver fibrosis, associated with hepatic stellate cells (HSCs), occurs when a healthy liver sustains damage, thereby impairing its function. NADPH oxidases (NOXs), specifically isoforms 1, 2, and 4, play a role in reactive oxygen species (ROS) production during hepatic injuries, resulting in fibrosis. Curcumin has shown strong potential in mitigating liver ...

Background: Numerous equations are applied in order to estimate the glomerular filtration rate (GFR). Objectives: This study aimed to spot the optimal equation that accurately estimates GFR and, therefore, the chronic kidney disease (CKD) stage in renal transplant patients. Methods: This cross-sectional study was conducted on 58 renal transplant patients. Their venous blood samples were obtained for serum creatinine and cystatin C determination used to calculate estimated GFR (eGFR). The average contrast of GFR in each equation was calculated using the Bland-Altman method. The correlation, bias, imprecision, and 10% and 30% accuracy were compared between the eGFR cystatin C and creatinine. Concordance between both equations for CKD staging was assessed. The classification of patients was also investigated. Results: Bland-Altman plots and bias demonstrated that eGFR by the abbreviated modification of diet in renal disease (Ab-MDRD) was the most accurate compared with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C, followed by CKD-EPI eGFR creatinine. With reference to CKD-EPI cystatin C, the imprecision of the equations was approximately similar to Ab-MDRD, and CKD-EPI creatinine is still better than the Cockcroft-gault (CG) formula. They also showed good 30% accuracy. Finally, our finding suggested that Ab-MDRD and CKD-EPI eGFR creatinine might be the best-performing equation in the classification of the CKD stages in a cutoff of 60 mL/min/1.73 m2. Conclusions: Due to the high cost and potential delay in measuring cystatin C, it would be much more appropriate to measure Ab-MDRD; after that, CKD-EPI eGFR creatinine as an alternative approach in order to facilitate rapid clinical decision in renal transplant patients.