Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives

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

Reference intervals for routine biochemical markers and body mass index: a study based on healthcare center database in northeastern Iran

Age‐ and sex‐specific reference intervals (RIs) for some biochemical tests may be useful for their interpretation, due to the variations in lifestyle and genetic, or ethnic factors. The aim of this study was to obtain RIs for some routine biochemical markers including a serum lipid profile, fasting blood glucose (FBG), aspartate and alanine aminotransferase (AST and ALT), uric acid, and body mass index (BMI) in subjects who attended primary healthcare centers. The large database of primary healthcare centers uses RIs to report results for children, adolescents, and young and old adults. RIs were obtained by using the indirect method, recommended by the CLSI Ep28‐A3 guidelines. RIs for FBG, BMI, and serum lipid profile, including triglyceride, total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol in people aged 18 to 120 years, were obtained without age/sex segmentation. RIs for serum AST, ALT, and uric acid were obtained without age segmentation, though these RIs were higher in males than females. The RIs for AST, ALT, and uric acid were higher in men, while the RIs for the other variables were similar in both sexes. This is the first study reporting the use of indirect RIs for BMI

Association between diabetes mellitus and rs2868371; a polymorphism of HSPB1

Introduction: Diabetes (DM) is a type of metabolic disorder that its types are generated by collectingof genetic and environmental risk agents. Here, the association between HSPB1 polymorphism as a genetic risk factor and DM was investigated. Methods: Total 690 participants from MASHAD cohort study population were recruited into the study.Anti-HSP27-level was assessed followed by genotyping using Taqman®-probes-based assay. Anthropometric, demographic and hematological/biochemical characteristics were evaluated. Kaplan-Meier curves were utilized, while logistic regression models were used to assess the association of the genetic variant with clinical characteristics of population. Results: Finds was shown there are meaningful differences among groups of age, height, waist circumference, systolic blood pressure, FBG,TG, HDL-C, and hs-CRP, and was no big -significant difference between theexists in different HSP27 SNP in the two studied groups (with and without DM), also was no remarkable relation between genetic forms of HSPB1and T2DM. This investigation was the first research that analyzed the relationship between the genetic type of the HSPB1 gene (rs2868371) and Type 2 diabetes (DM2). In our population, the CC genotype (68.1%) had a higher prevalence versus GC (26.6%) and GG (5.3%) genotypes and the data shown that no genetic difference of HSPB1 gene polymorphism (rs2868371) was related with DM2. Conclusion: HSPB1 polymorphism, rs2868371, was not associated with type 2 diabetes mellitus

The Effect of SP/NK1R on the Expression and Activity of Catalase and Superoxide Dismutase in Glioblastoma Cancer Cells

Introduction. Glioblastoma is the most malignant brain tumor with different therapeutic protocols, including surgery, radiotherapy, and chemotherapy. Substance P (SP), a peptide released by sensory nerves, increases cellular excitability by activating the neurokinin-1 receptor (NK1R) in several human tumor cells. Aprepitant is a potent and long-lasting NK1R antagonist, considered a new agent for inhibiting proliferation and induction of apoptosis in malignant cells. This study aimed to evaluate the effects of the SP/NK1R system on the expression and activity of catalase and superoxide dismutase (SOD) in the glioblastoma U87 cancer cell line. Methods. Cytotoxicity was measured by the resazurin test, 24 hours after treatment, with increasing aprepitant concentrations. The production of reactive oxygen species (ROS) was also measured 24 hours after treatment with SP and aprepitant. Enzymes activity of catalase and SOD was measured using the corresponding assay kits. Real-time PCR also measured their expression. Results. Aprepitant significantly reduced the viability of U87 cells in a concentration-dependent manner. ROS production was significantly reduced, and the activity of catalase and SOD increased after treatment with aprepitant. The expression of catalase and SOD enzymes also increased significantly in the presence of aprepitant. Conclusion. The present study showed that aprepitant inhibited SP’s oxidizing effects via inducing the antioxidant effects of catalase and SOD in the U87 cell line. Therefore, this drug might be introduced as a potential candidate for controlling glioblastoma cancer in animal models and clinical trials

Interaction between the genetic variant of rs696217‐ghrelin and food intake and obesity and dyslipidemia

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Individuals with the TT genotype at the locus had the lowest prevalence of obesity compared to other genotypes among the individuals. No significant relationship was found between the two groups regarding the lipid profile and TT genotype. Furthermore, no significant association was found between dietary intake and the genetic variant of rs696217-ghrelin in the population under study. Individuals with a TT or GT genotype appear to be at a higher risk of obesity, compared to those with a GG genotype. The results of the current study revealed a significant association between the genetic variant of rs696217-ghrelin and obesity; however, this gene did not correlate with the risk factors of cardiovascular diseases and dyslipidemia in the Iranian population

Investigating the predictive value of microRNA21 as a biomarker in induced myocardial infarction animal model

Background: Cardiovascular disease (CVD) is an important cause of morbidity and mortality worldwide. The risk factors for CVD can be unmodifiable, such as advancing age, sex, and genetic factors, or modifiable, like smoking, high blood pressure, abnormal sugar, and obesity. Biomarkers that are used clinically to make a diagnosis of myocardial ischemia include: cardiac enzymes like CKMB and troponin, and these can be used in combination with an electrocardiogram to make a diagnosis. Over the past few years, microRNA has also been used to improve the diagnosis of disease. In this study, we have assessed the use of miRNA-21-3p (miR-21-3p) for early and accurate diagnosis of acute myocardial infarction in a rat model. Methods: Twenty male Wistar rats, divided into 2 groups: 10 healthy ones and 10 induced myocardial infarction rats. Blood samples were taken from these two groups. Real-time PCR was used to measure the serum level of miR-21-3p. A ROC curve analysis was used to evaluate the utility of serum miR-21-3p to diagnose myocardial infarction (MI) in the rat model (AUC: 0.97 (0.91 to 1 at 95 CI) with 100 specificity and 88 sensitivity). Result: The mean CK-MB and troponin I levels in the control group were higher than AMI group significantly (P < 0.001). Serum expression of miR-21 in rats induced myocardial infarction was significantly higher than control group (p < 0.05). Conclusion: Overexpression of miR-21-3p is a particular importance of acute myocardial infarction (AMI) and can have a special place among the other microRNA in this field

High-dose vitamin D supplementation is related to an improvement in serum alkaline phosphatase in COVID-19 patients; a randomized double-blinded clinical trial

Abstract Background The benefits and harms of vitamin D supplementation in the treatment of COVID-19 have not yet been fully documented. In this study, we aimed to evaluate the effects of high-dose vitamin D supplementation on liver function tests in COVID-19. Method This double-blinded randomized clinical trial was conducted on 140 hospitalized patients aged > 30 years. Patients were randomly allocated to receive either intervention group (n = 70 receiving 50,000 IU of vitamin D capsules orally as a single dose and then 10,000 IU syrup daily from the second day of admission for 30 days) and the control group (n = 70 receiving 1000 IU vitamin D syrup orally per day). Liver function tests (LFT), including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and Lactate Dehydrogenase (LDH) were evaluated at baseline and at the end of the intervention. Decision tree analysis was performed to identify the predictors for change in liver enzymes. Results Among COVID-19 patients, a significant decrease was observed in serum level of ALP between intervention and placebo groups (p = 0.04). In addition, decision tree analysis revealed that GGT, temperature, serum magnesium level at baseline and gender were the most important predictors of ALT changes in COVID-19 patients. Conclusion High-dose vitamin D supplementation improved ALP markers among COVID-19 patients. More randomized controlled trials with longer follow-up times will be required

A large population‐based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study

Abstract Background Twelve‐lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population. Methods ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS. Results Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T‐wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff‐Parkinson‐White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T‐wave abnormalities, Wolff‐Parkinson‐White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P‐wave duration, and QRS duration between men and women indicated that there was a significant difference. Conclusions Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups