Background: Since there is currently no cure for amyotrophic lateral sclerosis (ALS), it is essential to search for diagnostic biomarkers and novel treatments to reduce the severity of this disease. One of these treatment approaches is stem cell transplantation Objective: This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing clinical and molecular data. Methods: This one-arm, single-center, open-label without a control group, prospective clinical trial, twenty-one confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6, MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment using ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) values and also molecular investigation by evaluating specific microRNAs expression (mir206, 133a-3p, 338-3p) in patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up period. Result: No serious adverse effects were reported during the study. Besides, significant improvement in FVC when compared the baseline with the end of the research and the p-value was (0.036), and stability in ALSFRS was observed, and the p-value was (p=0.16) following stem cell transplantation in patients; also, the mentioned microRNA expression was non-significant (p > 0.05) as reported as well. Conclusion: Our results demonstrated that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model. In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized. The mice were treated with MSCs, exosomes, Mesalazine, and a combination of them. Upon sacrificing the mice, colon and spleen tissues were isolated to assess the changes in the mice’s weight, colon length, spleen weight, and colitis’ pathological symptoms. IL-10 and IL-17 levels were measured, and Treg and Th17 cell percentages were determined as well. Furthermore, colon tissue was stained to investigate histopathological changes. In the groups that received MSCs, there was a significant reduction in the disease activity index and their combinations with exosomes and Mesalazine compared to the colitis group. Colon length increased in all groups except the exosome group. Histological measures were notably reduced in the MSC groups and their combinations. Significant increases in the IL-10 level of colon tissue and the proportion of Treg present in the spleen were observed in the groups receiving MSC and combination treatment. Furthermore, these groups showed a notable reduction in the percentage of spleen Th17 cells. However, IL17A decreased non-significantly in all groups. The results showed that intraperitoneal injection of UC-MSCs and their combination with exosome and Mesalazine in a murine colitis model improved the disease’s symptoms. Therefore, MSCs and their combination with exosomes can be a promising therapeutic approach along with other common drugs for IBD, but exosomes alone could not significantly reduce the symptoms of colitis.

Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. Methods: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). Results: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. Conclusions: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial. In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1×  PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis. we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group. These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.

Mesenchymal stem cells (MSCs) have garnered significant attention in modern medicine as a potentially effective therapeutic intervention, owing to their distinctive characteristics, including the ability to self-renew, exhibit multipotency, elicit immunomodulatory effects, and promote tissue repair. MSCs are being studied extensively for their potential use in a wide range of clinical applications, including regenerative medicine, immunotherapy, and tissue engineering. In this chapter, we provide a comprehensive overview of the biology, potential, and function of MSCs, highlighting their role in modulating the immune system, promoting tissue repair, and restoring homeostasis in various disease conditions. We also discuss the challenges and limitations associated with MSC-based therapies, including issues related to their isolation, expansion, and delivery. Further research is needed to fully understand the mechanisms underlying MSCs’ therapeutic effects and to optimize their clinical application. Nevertheless, MSCs hold great promise as game-changers in modern medicine, and their potential to revolutionize the field of regenerative medicine and immunotherapy cannot be overlooked.

Amyotrophic lateral sclerosis (ALS) is a rare deadly progressive neurological disease that primarily affects the upper and lower motor neurons with an annual incidence rate of 0.6 to 3.8 per 100,000 people. Weakening and gradual atrophy of the voluntary muscles are the first signs of the disease onset affecting all aspects of patients’ lives, including eating, speaking, moving, and even breathing. Only 5-10% of patients have a familial type of the disease and show an autosomal dominant pattern, but the cause of the disease is unknown in the remaining 90% of patients (Sporadic ALS). However, in both types of disease, the patient’s survival is 2 to 5 years from the disease onset. Some clinical and molecular biomarkers, Magnetic Resonance Imaging (MRI), blood or urine test, muscle biopsy, and genetic testing are complementary methods for disease diagnosis. Unfortunately, with the exception of Riluzole, the only medically approved drug for the management of this disease, there is still no definitive cure for it. In this regard, the use of Mesenchymal Stem Cells (MSCs) for the treatment or management of the disease has been common in preclinical and clinical studies for many years. MSCs are multipotent cells having immunoregulatory, anti-inflammatory, and differentiation ability that makes them a good candidate for this purpose. This review article aims to discuss multiple aspects of ALS disease and focus on MSCs’ role in disease management based on performed clinical trials.

Abstract Background Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild–moderate COVID-19-induced ARDS patients. Methods Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × $${10}^{6}$$ 10 6 cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. Results During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period. Conclusion Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1× cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells. These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

BackgroundAcute respiratory distress syndrome (ARDS) is the devasting complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, Mesenchymal Stem Cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and efficacy of three injections of Umbilical Cord-derived MSCs (UC-MSCs) in mild-moderate COVID-19-induced ARDS patients.MethodsTwenty confirmed COVID-19 patients with mild to moderate ARDS degree (using the WHO guideline for ARDS classification) entered the study and were randomly divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × \({10}^{6}\) cells/kg BW per injection) every other day. Respiratory markers, CRP levels and some serum cytokines were assessed four times (days of 0,5,10 and 17) during the 17 days follow-up period.ResultsDuring the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO 2 /FIO 2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P<0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 was observed. Also, no significant changes were observed in CT scan images of patients during the study period.ConclusionOur obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results.Trial registrationThis clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).

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Background: Several studies indicate contribution of hypothalamus-pituitary-adrenal (HPA) axis in multiple sclerosis (MS) disease. This study was designed to determine whether there is an effective difference in pituitary height, shape, and anterior-posterior diameter (APD) between patients with MS and the control group. Methods: In this study, sagittal pituitary height and APD of 134 men and women (64 patients with MS and 70 healthy subjects as control group) were measured by T1 sequence magnetic resonance imaging (MRI). All the subjects were free of sellar or parasellar pathology without a history of surgical intervention or prolactin affecting drugs like bromocriptine and cabergoline or corticosteroid consumption. Results: Mean height of pituitary gland was 6.62 ± 1.43 and 5.78 ± 1.15 mm for patients and the control group, respectively, and the difference between the two groups was statistically significant (P = 0.001). Mean APD was 10.40 ± 1.29 mm for the group of patients and 10.25 ± 1.41 mm for the control group, respectively, without significant differences. 46.9%, 37.5%, and 15.6% of patients had flat, convex, and concave hypophyseal surfaces, respectively. This rate was 50%, 30%, and 20% among the control group, respectively. There was no significant difference between our measurements among patients on whom imaging study was performed at time of disease onset with others. Conclusion: Mean height of pituitary gland among patients with MS was significantly greater than the control group (P = 0.001). So can we consider the same etiology for pituitary hypertrophy among patients with MS as a hypothesis?

Height, shape and anteroposterior diameter of normal pituitary gland in 15 to 40 years old population

Background and Aim: Aspergillosis are the most prevalent cause of the respiratory infections. These fungi show invasive aspergillosis(IA) in immunocompromised patients. The number of immunocompromised patients are increasing due to immunodisorder illnesses, grafts and immunosuppressor drugs, so, rapid identification methods are very important. The aim of this study was to detect the Aspergillus spp. In fluid samples by nested PCR, and compare with culture and direct smear. Materials and Methods: Conventional detection methods such as culture and direct smear are unsensitive and time consuming. Some methods such as immunodetecting methods have high false positive and are unreliable. Nowadays, molecular methos and PCR are very helpful. These methods are both sensitive and reliable and very rapid. In this study, we used Nested PCR, culture and direct smear to detect Aspergillus spp in BAL fluid samples. Results: This research is a descriptive-comparative study and has been done for rapid identification of fungi related to Aspergillosis such as culture, direct smear and nested- PCR. Findings of this study show that positive results by nested-PCR were more effective and sensitive than culture and direct smear.Conclusions: We found that positive results by PCR were more effective and sensitive than two other methods.

PURPOSE:To study the presence of the herpes simplex virus type 1 (HSV-1) glycoprotein D gene in tear films of Iranian patients with herpetic keratitis.METHODS:Twenty-five tear film and eye swab specimens from 25 herpetic keratitis patients and 10 specimens from 10 healthy volunteers were collected in the Farabi Eye Hospital, Tehran, Iran. HSV-1 DNA was detected by using the nested polymerase chain reaction (nPCR) method. Viral isolation was done using conventional viral techniques. A monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) was used for confirmation of positive cytopathic effect cell culture. The results of a diagnosis by an ophthalmologist team were compared with those of nPCR.RESULTS:HSV-1 DNA was identified in tear films of 88% (23/25) of suspected herpetic keratitis patients. All healthy controls (100%) had negative PCR results. HSV-1 was isolated in cell culture and confirmed by ELISA in 12% (3/25) of herpetic keratitis patients who had epithelial keratitis. The kappa value showed a high level of agreement between ophthalmologist team diagnosis and the PCR results (kappa = 0.86, P < 0.0001).CONCLUSIONS:nPCR is a sensitive, rapid, and powerful tool for detection of HSV-1 DNA in tear films of ocular herpetic keratitis patients and can serve as a supplemental method for diagnosis of herpetic keratitis infection.