Hamid Reza Rahimi

Purpose: Recalcitrant diabetic foot ulcers (DFUs) remain difficult to heal and impose substantial clinical and economic burdens. This exploratory, four-arm, parallel-group randomized pilot trial aimed to evaluate whether combining platelet-rich plasma-fibrin glue (PRP‑FG) with a novel repairing gel enhances healing outcomes in DFUs compared with standard care and single‑agent therapies. Patients and Methods: In this study, twenty patients with DFUs unresponsive to at least four weeks of standard treatment were randomized using computer-generated blocks with allocation concealment to receive PRP‑FG alone, repairing gel alone, the combination therapy, or standard care. Allogeneic PRP‑FG was prepared by gradient‑density centrifugation. The repairing gel contained multiple active components, including vitamins A, B3, and C, collagen, glycine, organic acids, sodium alginate, carboxymethyl cellulose, benzoic acid, gentian violet, methylene blue, triethanolamine, bromelain, allantoin, and dimethyl sulfoxide. Wound healing rate over 12 weeks served as the primary outcome, assessed weekly by a blinded evaluator. Results: Nineteen patients completed the 12‑week follow‑up. Complete epithelialization occurred in 100% (5/5) of participants receiving the combined therapy, 20% (1/5) of those receiving the repairing gel alone, and 0% (0/5) in the PRP‑FG alone and standard care groups. The combined therapy significantly accelerated ulcer healing compared with all other groups (p < 0.05). These findings are preliminary and derived from a small pilot sample. No serious adverse events were observed. Conclusion: This exploratory pilot trial suggests that combined PRP‑FG and repairing gel therapy may promote superior healing of recalcitrant DFUs compared with standard care or single‑agent treatments. Larger, multicenter clinical trials are warranted to validate these preliminary findings.

Objective(s): Platelet-rich plasma (PRP) is widely used in regenerative medicine due to its high concentration of bioactive growth factors; however, its short shelf life limits its clinical applicability. Lyophilization has been proposed to extend PRP stability, but its impact on biological efficacy remains unclear. This study evaluated whether lyophilization alters the biochemical composition and regenerative function of PRP derived from expired platelet units unsuitable for transfusion.Materials and Methods: Pooled isogroup PRP was processed as either liquid PRP or lyophilized PRP. Growth factors (FGF-1, PDGF, VEGF) and endotoxin levels were quantified. Biological activity was assessed in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) using MTT assays, in vitro wound closure, gene expression analysis (MMP-1, MMP-3, Ang1, PDGFR), and CD31 immunocytochemistry at 5% and 10% concentrations, with fetal bovine serum (FBS) as a control.Results: Lyophilization resulted in moderate reductions in FGF-1, PDGF, and VEGF relative to Liquid-PRP (P<0.05), while endotoxin levels remained acceptable. In HDFs, liquid-PRP induced higher MMP-1 and MMP-3 expression, whereas lyophilized-PRP promoted lower but sufficient expression, consistent with controlled extracellular matrix remodeling, with comparable wound-closure outcomes between PRP groups. In HUVECs, lyophilized PRP preserved cell viability, migration, and CD31 expression, comparable to liquid PRP and FBS. Angiogenic gene expression showed a concentration-dependent response, with maximal activation at 5% PRP, and no functional impairment after lyophilization (P<0.05).Conclusion: Despite a moderate reduction in growth factors, lyophilized PRP retained regenerative efficacy, supporting lyophilization as a viable strategy for the stable, sustainable reuse of PRP.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective loss of motor neurons (MNs), leading to progressive muscle weakness, atrophy, and ultimately paralysis. This review provides a comprehensive overview of the molecular mechanisms underlying ALS pathogenesis, the genetic mutations associated with both familial and sporadic forms of the disease, and the latest therapeutic strategies aimed at mitigating disease progression. mutations in genes such as C9orf72, SOD1, TARDBP, and FUS have been implicated in ALS, with an intricate interplay of protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation contributing to motor neuron degeneration. While current FDA-approved treatments such as Riluzole and Edaravone offer only modest benefits and do not significantly halt disease progression. Emerging therapies, including gene therapies (e.g., antisense oligonucleotides (ASOs) and CRISPR/Cas9, stem cell-based approaches, and neurotrophic factor supplementation, are demonstrating promising results in preclinical and early-phase clinical trials. novel approaches aim to target, modulate, and promote regeneration, renewed hope for future ALS treatments. However, several challenges remain, including effective delivery methods, safety concerns, and the inherent complexity of ALS pathology, ongoing research continues to explore these innovative interventions with the goal of improving clinical outcomes for patients. This review highlights the importance of personalized therapeutic approaches and underscores the necessity of continued innovation in ALS research, with the ultimate goal of developing disease-modifying therapies and, potentially, a cure for this fatal condition. Amyotrophic Lateral Sclerosis, Neurodegenerative Diseases, C9orf72 Mutation, SOD1 Mutation, Riluzole This comprehensive review article presents an in-depth analysis of the molecular pathogenesis of Amyotrophic Lateral Sclerosis (ALS), emphasizing the complex interplay of genetic mutations, protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation that collectively drive motor neuron degeneration. By systematically categorizing ALS subtypes based on genetic, clinical, and molecular characteristics, the article elucidates the diverse mechanisms underlying both familial and sporadic forms of the disease. Notably, it highlights key genetic mutations such as those in C9orf72, SOD1, TARDBP, and FUS and details how these contribute to disease pathology through distinct molecular pathways. The review integrates recent advances in understanding ALS heterogeneity and the impact of gene-environment interactions and epigenetic factors, underscoring the necessity for personalized therapeutic approaches. A novel aspect of this review is its comprehensive coverage of cutting-edge therapeutic strategies targeting ALS at the molecular level, including gene therapies like antisense oligonucleotides (ASOs), RNA interference, and CRISPR/Cas9 gene editing, alongside stem cell-based treatments and antibody-mediated interventions. The article critically evaluates the current state of FDA-approved drugs, such as Riluzole and Edaravone, noting their limited efficacy, while bringing to light promising preclinical and clinical trial data on novel treatments aimed at halting or reversing disease progression. Furthermore, it discusses the challenges inherent in delivering therapies across the blood-brain barrier, safety concerns, and the need for robust clinical trial designs. By integrating molecular insights with therapeutic innovations and clinical perspectives, this review advances the field by providing a valuable roadmap for future research focused on developing effective, disease-modifying treatments for ALS.

Background MicroRNAs (miR) regulate post-transcriptional gene expression with an established role in cancer development, angiogenesis, invasion, and metastasis. miR-21 is an oncogenic miR that targets p53 and promotes tumor development. We aim to assess mir-21 expression in bladder cancer (BCa) and compare it to grossly normal-appearing tumor-adjacent tissue and controls. Methods This case–control study was implemented from December 2019 to July 2021. We collected 72 specimens of 36 BCa cases (36 specimens of tumoral tissue and 36 specimens of grossly normal-appearing adjacent tissue) and nine specimens from 9 control participants. After total mRNA extraction, microRNA expression was evaluated by Stem-loop real-time RT-PCR. Results Among the 45 participants, the mean ages in the BCa (36 patients) and control groups (9 patients) were 58.46 ± 16.69 and 56.89 ± 14.92, respectively. The mean expression of miR-21 was 1.8 ± 1.5, 2.8 ± 1.2, and 1.0 ± 0.5 in tumoral tissue, tumor-adjacent grossly normal tissue, and control specimens, respectively. miR-21 expression was higher in tumoral and tumor-adjacent tissues than in controls, with smokers exhibiting significantly elevated levels across all groups (p = 0.037). Additionally, miR-21 expression was significantly higher in high-grade versus low-grade BCa tumors (p = 0.025), with tumoral tissue expression levels of 1.9 ± 1.2 and 1.5 ± 1.3, respectively, and tumor-adjacent tissue levels of 2.7 ± 1.2 and 1.95 ± 1.4, respectively. In the control group, older age was associated with reduced expression of miR-21, whereas in BCa patients, the expression of miR-21 increased with aging (p < 0.05). Conclusion miR-21 expression was higher in the tumor-adjacent tissue than in tumoral tissue and control specimens. The study recognizes certain limitations, such as a limited control group and possible sample loss, which might influence the strength and applicability of the findings.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction, with chronic inflammation playing a central pathogenic role. Mesenchymal stem cells (MSCs) possess therapeutic potential through immunomodulatory and tissue-reparative properties. This study aimed to evaluate the safety and efficacy of intravenous allogeneic umbilical cord-derived MSCs (UC-MSCs) in patients with T2DM. Eleven adults with T2DM (disease duration ≥ 10 years; HbA1c ≤ 8%) received a single intravenous infusion of 1 × 10⁸ UC-MSCs. This open-label pilot trial assessed safety (adverse events, hematologic and metabolic parameters) and efficacy (glycemic control and inflammatory gene expression) over a 2-month follow-up period. UC-MSCs were isolated under standardized conditions. UC-MSC transplantation in patients with T2DM was well tolerated, with only transient fever (36.3%) and mild muscle pain (18.2%) reported. The intervention resulted in significant metabolic improvements, including a 2.1% reduction in HbA1c (P = 0.00095) and a decrease in fasting glucose by 93.7 mg/dL (P = 0.00097). Treatment also modulated inflammatory pathways, as evidenced by upregulating of IKBα (1.76-fold, P = 0.0067) and downregulating of TNFα (0.62-fold) and IL-6 (0.65-fold). Variability in IKBα expression accounted for 48% of the variance in HbA1c (r = -0.69). Two distinct response patterns were observed: improvement in insulin sensitivity (7/11) via NF-κB suppression, and enhancement of β-cell function (3/11). Allogeneic UC-MSC transplantation appears safe and significantly improves glycemic control in patients with T2DM. The heterogeneity in patient responses underscores the importance of stratification based on inflammatory status. These findings support UC-MSC therapy as a promising disease-modifying strategy and highlight the need for larger, controlled clinical trials.

: Cancer, the second greatest cause of mortality worldwide, frequently causes bone metastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord compression. These injurious incidents leave uncomfortably in each of the cancer patient’s life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and exhibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various biological processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Diabetes mellitus (DM) is a significant public health problem and is one of the most challenging medical conditions worldwide. It is the severe complications that make this disease more intricate. A diabetic wound is one of these complications. Patients with diabetes are at higher risk of developing diabetic foot ulcers (DFU). Due to the ineffectiveness of Conventional treatments, growth in limb amputation, morbidity, and mortality have been recognized, which indicates the need for additional treatment. Mesenchymal stem cells (MSCs) can significantly improve wound healing. However, there are some risks related to stem cell therapy. Exosome therapy is a new treatment option for diabetic wounds that has shown promising results. However, an even more advanced form called cell-free therapy using exosomes has emerged. This upgraded version of stem cell therapy offers improved efficacy and eliminates the risk of cancer progression. Exosome therapy promotes wound healing from multiple angles, unlike traditional methods that primarily rely on the body’s self-healing ability and only provide wound protection. Therefore, exosome therapy has the potential to replace conventional treatments effectively. However, further research is necessary to distinguish the optimal type of stem cells for therapy, ensure their safety, establish appropriate dosing, and identify the best management trail. The present study focused on the current literature on diabetic wound ulcers, their treatment, and mesenchymal stem cell and exosome therapy potential in DFU.

Objective: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes with no consumption of alcohol. Recently, curcumin is a natural polyphenol found in turmeric has been examined for the treatment of NAFLD. This study aimed to assess the efficacy of 160 mg/day nano-micelle curcumin on the amelioration of NAFLD by measuring liver enzymes.Materials and Methods: Patients with NAFLD were randomly divided into curcumin (intervention group n=33) and placebo (n=33) groups and at the end of the study, the data of 56 participants who completed the 2-month intervention were analyzed. Laboratory tests and questionnaires were used to gather information. Both groups received recommendations for lifestyle modification, and were advised to other necessary advices. Patients in the curcumin group received 160 mg/day of nano micelle curcumin in two divided doses for 60 days. The 2 groups were followed up for two months and clinical and laboratory indices were compared.Results: Our data showed a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the curcumin group (p<0.01) as well as a significant difference between the groups before and after the intervention in curcumin group (p<0.05). Interestingly, a meaningful decrease in AST serum level was observed in the intervention group (p<0.01).Conclusion: Our study demonstrated that short-term supplementation with nano-micelle curcumin results in the reduction of AST and ALT and is beneficial for the treatment of NAFLD.

Background and Objective: Incomprehensive studies have examined the therapeutic and side effects of curcumin on the treatment of debilitating diseases, such as Rheumatoid Arthritis (RA). This study aimed to explore the anti-inflammatory effects of curcumin on RA. Materials and Methods: This double-blind clinical trial was carried out on 64 RA patients with ...