In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found that Figure 2A was the same as the one that has already been published and it was confusing. The following figure's legend is corrected in reference 9. The authors would like to apologies for any inconvenience caused.
OBJECTIVE: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-ß (TGF-ß) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-ß-stimulated expression of CHSY1 and CHST11 and associated signaling pathways using an in vitro model. MATERIALS AND METHODS: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 µM) prior to being stimulated with TGF-ß (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1. RESULTS: Our research results indicated that atorvastatin inhibited TGF-ß-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-ß-stimulated ROS production and weakened TGF-ß-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-ß- Smad2C pathway. CONCLUSION: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.
Epithelial Mesenchymal Transition (EMT) is a dedifferentiation process implicated in many physio-pathological conditions including tumor transformation. EMT is regulated by several extracellular mediators and under certain conditions it can be reversible. Autophagy is a conserved catabolic process in which intracellular components such as protein/DNA aggregates and abnormal organelles are degraded in specific lysosomes. In cancer, autophagy plays a controversial role, acting in different conditions as both a tumor suppressor and a tumor-promoting mechanism. Experimental evidence shows that deep interrelations exist between EMT and autophagy-related pathways. Although this interplay has already been analyzed in previous studies, understanding mechanisms and the translational implications of autophagy/EMT need further study. The role of autophagy in EMT is not limited to morphological changes, but activation of autophagy could be important to DNA repair/damage system, cell adhesion molecules, and cell proliferation and differentiation processes. Based on this, both autophagy and EMT and related pathways are now considered as targets for cancer therapy. In this review article, the contribution of autophagy to EMT and progression of cancer is discussed. This article also describes the multiple connections between EMT and autophagy and their implication in cancer treatment.
Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.
OBJECTIVE: Disruption of cholesterol homeostasis in Alzheimer's disease (AD) plays a crucial role in disease pathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treating cognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs on specific metabolites associated with brain cholesterol homeostasis in an AD rat model. MATERIALS AND METHODS: In this experimental study, animals were divided into three groups: control, AD, and AD+MSCs. AD was induced using amyloid beta (Aß) and confirmed through the Morris water maze (MWM) behavioural test and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast and adipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gas chromatography-mass spectrometry (GC)-MS and compared among the groups. RESULTS: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to the AD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbances in the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol, 27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment with MSCs resulted in significant alterations in the levels of these metabolites. CONCLUSION: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterol homeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance of investigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlying mechanisms of the therapeutic efficacy of MSCs in AD.
Mesenchymal stem cells (MSCs) have potential as a viable treatment option in the field of regenerative medicine, but MSC-based therapy needs to be more efficient. Preconditioning is a method to improve MSC-based therapy, and dimethyl fumarate (DMF) - an agent that can enhance the antioxidative capacity of cells - can be considered for preconditioning of MSCs. In this study, we treated bone marrow-derived MSCs with DMF and evaluated their proteome using bottom-up proteomics. The MSCs were exposed to 10 µM DMF for 24 h, followed by lysis with an SDS solution, digestion with trypsin using an s-trap column, and analysis using nanoLC-MS/MS, which identified 2262 proteins with confidence. Bioinformatic analysis of the identified proteins revealed 47 upregulated proteins and 81 downregulated proteins upon DMF treatment. Pathway enrichment analysis suggested a possible decrease in autophagy and a decrease in the activity of the TCA cycle, while indicating a potential increase in proliferation and antioxidant activity in DMF-treated MSCs compared to untreated MSCs. Our findings suggest that DMF can enhance the proliferation of MSCs and increase their stability, and that preconditioning could improve the therapeutic efficacy of MSCs for the treatment of regenerative diseases.
Background and Aims: Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway. Methods: Total RNA was extracted from 40 samples of breast tumor tissues and their respective controls. The expression level of lncRNAs CASC2, NEAT1, and LINC00299 was quantified using reverse transcription-polymerase chain reaction (RT-PCR). The ratio of the spliced form of XBP1 to its unspliced form (XBP1u) was determined by PCR and electrophoresis. Results: The results showed a 2.8-fold increase in the ratio of XBP1s/u in breast cancer tissues compared to adjacent nonmalignant samples (p < 0.05). Additionally, the level of lncRNAs NEAT1, CASC2, and LINC00299 in breast tumor tissues increased significantly by twofold, 1.5-fold, and 2.3-fold, respectively, compared to adjacent nonmalignant samples (p < 0.05). Conclusions: Based on the association between the expression of lncRNAs CASC2, LINC00299, and NEAT1 and the XBP1s/u ratio, these lncRNAs could be potential regulators of the UPR pathway. Also, CASC2 and NEAT1 genes could be suggested as suitable biomarkers to distinguish cancerous tissue from noncancerous breast tissue due to their significant increase in expression in cancerous samples compared to adjacent noncancerous.
AIM: Mesenchymal stem cells (MSCs) have emerged as an intriguing candidate in cell therapy for treating neurodegenerative diseases, including Alzheimer's disease (AD). To achieve the maximum efficiency of cell therapy, determining the optimal dose of MSCs is essential. This study was conducted to assess the dose-dependent therapeutic response of MSCs against pathological and behavioral AD-associated alterations. METHODS: Aß1-42 was injected intrahippocampally to establish an AD rat model. The MWM test was utilized to evaluate the animal's behavioral functions after receiving low and high doses of MSCs in the hippocampus region. ELISA and RT-qPCR were also employed to assess the concentration of markers related to antioxidant activity and inflammation and the gene expression related to apoptosis in the hippocampus region, respectively. RESULTS: Low-dose MSC transplantation by increasing the concentrations of the antioxidant GSH, the anti-inflammatory cytokine IL-10, as well as by lowering the concentrations of TNF-α, and the expression levels of apoptotic factors (Bax and caspase 3), exerted a neuroprotective effect in the hippocampus of AD rats and relatively ameliorated spatial learning and memory impairments. However, increasing the dose of MSCs decreased the therapeutic benefits of these cells and had no significant effect on the recovery of behavioral disorders. CONCLUSION: Our findings reveal the dose-dependent neuroprotective effect of MSCs in AD. The therapeutic response of MSCs to ameliorate the pathological and behavioral alterations associated with AD is attenuated when the dosage of MSCs is increased.
Alzheimer Disease , Mesenchymal Stem Cells , Neuroprotective Agents , Animals , Rats , Amyloid beta-Peptides , Alzheimer Disease/therapy , Antioxidants
In recent years, extracellular vesicles (EVs) have gained attention for their potential as biomarkers for the early diagnosis and treatment of various diseases. Traditionally, EV isolation has relied exclusively on ultracentrifugation. However, alternative enrichment methods such as size-exclusion chromatography (SEC) and polyethylene glycol-based precipitation have been introduced. This study utilized SEC as a characterization tool to assess the efficiency of EV isolation. Urinary EVs isolated from human urine using centrifugation (40,000 × g) were analyzed using an SEC column with a pore size of 1000 Å, an inner diameter of 7.8 mm, and a length of 300 mm. The EVs were detected sequentially using UV (280 nm) and fluorescence (λex/em = 550 nm/565 nm); the EVs were observed at approximately 6 min, while the proteins were observed at approximately 12 min. The repeated centrifugation enrichment steps resulted in an increase in EV peaks and a decrease in protein peaks. SEC analysis of the enriched EV samples confirmed that a four-cycle repetition of centrifugation is necessary for successful EV enrichment and removal of non-EV proteins from 40 mL of human urine.
Extracellular Vesicles , Humans , Chromatography, Gel , Centrifugation
AIM: Transplantation of mesenchymal stem cell (MSC) has been suggested to be a promising method for treating neurodegenerative conditions, including Alzheimer's disease (AD). However, the poor survival rate of transplanted MSCs has limited their therapeutic application. This study aimed to evaluate whether preconditioning MSCs with dimethyl fumarate (DMF), a Nrf2 inducer, could enhance MSC therapeutic efficacy in an amyloid-ß (Aß1-42)-induced AD rat model. METHODS: The survival and antioxidant capacity of MSCs treated with DMF were assessed in vitro. Aß1-42 intrahippocampal injection was used to create a rat model of AD. Following the transplantation of MSCs preconditioned with DMF and using the Morris blue maze test, spatial learning and memory were assessed. Using RT-qPCR, we evaluated the gene expression related to apoptosis and neurotrophins in the hippocampus region. RESULTS: Treatment with DMF enhanced cell survival and Nrf2 protein expression in MSCs in vitro. Preconditioning with DMF also enhanced the efficacy of transplanted MSCs in rescuing learning and spatial memory deficits in Aß-AD rats. Besides, DMF preconditioning enhanced the neuroprotective effect of transplanted MSCs in the hippocampus of rats treated with Aß1-42 by decreasing the expression of apoptotic markers (Bax, caspase 3, and cytochrome c), and elevating the expression of the anti-apoptotic marker Bcl2 and neurotrophins, including BDNF and NGF. CONCLUSION: Preconditioning MSCs with DMF boosted the therapeutic efficacy of these cells; therefore, it could serve as a targeted strategy for increasing the therapeutic efficacy of MSCs in treating neurodegenerative disorders, including AD.
Alzheimer Disease , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Rats , Animals , Alzheimer Disease/genetics , Dimethyl Fumarate/pharmacology , NF-E2-Related Factor 2/metabolism , Mesenchymal Stem Cells/metabolism , Spatial Memory , Brain/metabolism , Nerve Growth Factors/metabolism , Mesenchymal Stem Cell Transplantation/methods , Disease Models, Animal
The purpose of current study was to elucidate polyphenol tannic acid effect on renal function and activity of the renin-angiotensin system after unilateral ureteral obstruction (UUO). Male Wistar rats were divided into three groups of six randomly: 1) Sham, 2) UUO, and 3) UUO + Tannic acid. Rats in the UUO and UUO + Tannic acid groups experienced unilateral ureteral obstruction. In the Sham group, the abdominal cavity was exposed without UUO induction. In the UUO + Tannic acid group, animals received tannic acid (20 mg/kg) intraperitoneally, 6 and 12 h after clamping the left ureter and 6 and 12 h after the right nephrectomy. Blood samples were taken to measure blood urea nitrogen (BUN) and creatinine levels. Kidney tissue samples were obtained for assessment of oxidative stress, inflammatory indices and the levels of renin-angiotensin system components. Tannic acid administration significantly improved UUO-induced kidney dysfunction (serum BUN: 66.42 ± 14.414 mg/dl, p < 0.05; serum creatinine: 1.67 ± 0.258 mg/dl, p < 0.05), oxidative stress (MDA level: 95.29 ± 37.35 µmol/g tissue, p < 0.05; SOD activity: 59.82 ± 13.41 U/g protein, p < 0.01) and inflammation (renal TNF-α: 57.05 ± 15.653 pg/g tissue, p < 0.05; renal IL-6: 117.015 ± 24.076 pg/g tissue, p < 0.001). The treatment caused a reduction in the amount of renal angiotensinogen, renin and ACE genes expression compared to the UUO group (Angiotensinogen: 8.9 ± onefold, p < 0.05, Renin: 6.5 ± 1.14 fold, p < 0.05, ACE: 4.9 ± 0.64 fold, p < 0.05). Angiotensin II type 1 receptor protein levels decreased in the tannic acid-treated rats in comparison with the UUO group (0.61 ± 0.136, p < 0.05). According to the result of the current study, tannic acid considerably attenuated the complications of unilateral ureteral obstruction through renin-angiotensin system modulation. Trial registration: IR.TUMS.MEDICINE.REC.1400.802.
Ureteral Obstruction , Male , Rats , Animals , Ureteral Obstruction/complications , Ureteral Obstruction/drug therapy , Rats, Wistar , Renin/genetics , Angiotensinogen/metabolism , Angiotensinogen/pharmacology , Kidney , Signal Transduction , Fibrosis
BACKGROUND: Evidence show that the recommended dose of zinc may not be sufficient for controlling pathological conditions such as type 2 diabetes mellitus (T2DM). AIM: This study aimed to evaluate the effects of zinc supplementation on the oxidative status in overweight T2DM. In addition, the routine glycaemic parameters were determined and compared in zinc-treated and placebo groups. METHODS: In this randomised, double-blind, placebo-controlled trial, 70 patients with T2DM were selected. They were divided into two groups for supplementation of 50 mg zinc gluconate or placebo (zinc group, n=35; placebo group, n=35) per day for 8 weeks. Blood samples were collected from all the individuals in the zinc group and controls for analysis. RESULTS: The results showed that zinc supplementation to patients with T2DM for 8 weeks significantly inhibited serum levels of lipid peroxidation (25%), nitrotyrosine (30%) and total oxidant status levels (25%, p<0.05). Nevertheless, the total antioxidant capacity was significantly elevated (16%) following zinc intake by patients with T2DM. CONCLUSIONS: These data, together with our previous report, may suggest that the control in the glycaemic condition in overweight patients with T2DM is correlated with the antioxidative/oxidative balance following intake of 50 mg zinc supplementation for 8 weeks. Under these circumstances, the clinical and glycaemic indices, including fasting blood glucose, insulin, haemoglobin A1c and homeostasis model of assessment-insulin resistance, were controlled. TRIAL REGISTRATION NUMBER: IRCT2015083102.
Diabetes Mellitus, Type 2 , Humans , Antioxidants , Overweight , Zinc , Blood Glucose , Insulin , Dietary Supplements , Double-Blind Method
INTRODUCTION: Regenerative medicine involves the replacement of damaged cells, tissues, or organs to restore normal function. Mesenchymal stem cells (MSCs) and exosomes secreted by MSCs have unique advantages that make them a suitable candidate in the field of regenerative medicine. AREAS COVERED: This article provides a comprehensive overview of regenerative medicine, focusing on the use of MSCs and their exosomes as potential therapies for replacing damaged cells, tissues, or organs. This article discusses the distinct advantages of both MSCs and their secreted exosomes, including their immunomodulatory effects, lack of immunogenicity, and recruitment to damaged areas. While both MSCs and exosomes have these advantages, MSCs also have the unique ability to self-renew and differentiate. This article also assesses the current challenges associated with the application of MSCs and their secreted exosomes in therapy. We have reviewed proposed solutions for improving MSC or exosome therapy, including ex-vivo preconditioning strategies, genetic modification, and encapsulation. Literature search was conducted using Google Scholar and PubMed databases. EXPERT OPINION: Providing insight into the future development of MSC and exosome-based therapies and to encourage the scientific community to focus on the identified gaps, develop appropriate guidelines, and enhance the clinical application of these therapies.
Exosomes , Mesenchymal Stem Cells , Humans , Regenerative Medicine
BACKGROUND: In this study, a comparison between centrally and systemically administered erythropoietin (EPO) was performed on nephroprotection during hemorrhagic shock (HS) in male rats. METHODS: Male rats were allocated into four experimental groups. (1) Sham; a guide cannula was inserted into the left lateral ventricle and other cannulas were placed into the left femoral artery and vein. (2) HS; stereotaxic surgery was done to insert a cannula in the left lateral ventricle and after a 7-day recovery; hemorrhagic shock and resuscitation were performed. (3) EPO-systemic; the procedure was the same as the HS group except that animals received 300 IU/kg erythropoietin into the femoral vein immediately before resuscitation. (4) EPO-central; animals was treated with erythropoietin (2 IU/rat) into the left lateral ventricle before resuscitation. Arterial oxygen saturation (SaO2) was measured during experiments. Urine and renal tissue samples were stored for ex-vivo indices assessments. RESULTS: Erythropoietin (systemically/centrally administered) significantly improved SaO2, renal functional and oxidative stress parameters and decreased renal inflammatory (TNF-α and IL-6) mRNA expression compared to the HS group. EPO-treated groups showed a decrease in active form of caspase-3 protein level and an increase in autophagy activity in comparison with the HS group. CONCLUSION: Considering the fact that the effective dose of systemic EPO (300 IU/kg) was roughly 50 times higher than that of central administration (2 IU/rat), centrally administered EPO was accompanied by more advantageous consequences than systemic way. EPO is likely to act as a neuro-modulator or neuro-mediator in the central protection of organs including the kidneys.
Erythropoietin , Shock, Hemorrhagic , Rats , Male , Animals , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/metabolism , Erythropoietin/pharmacology , Kidney/metabolism , Tumor Necrosis Factor-alpha/pharmacology
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most common class of medicines used for the treatment of major depression. Recent studies have reported an association between depression and inflammation and suggested the significant effects of SSRIs on inflammatory processes. METHODS: The current study aimed to evaluate the effects of fluoxetine, an SSRI, on the level of inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the rat serum and RAW264.7 mouse macrophage cell line, using ELISA sandwich assays. Also, the expression of inflammatory genes, including JAK/STAT3 and TLR4/JNK, was examined in macrophages, using real-time quantitative reverse transcription PCR to determine the potential mechanism of fluoxetine in inflammation. The rats received fluoxetine (10, 20, and 40 mg/kg) 30 min before lipopolysaccharide (LPS) treatment for 90 min. The cells received different doses of fluoxetine (5, 10, and 20 µg/mL) before stimulation with LPS for 24 or 48 h. RESULTS: The serum concentrations of IL-1ß, IL-6, and TNF-α were reduced in rats and cells treated with fluoxetine. Following fluoxetine administration, the expression of JAK/STAT3 and TLR4/JNK genes was significantly decreased in the RAW264.7 cells treated with LPS for 24 h. However, after 48 h of treatment with LPS, fluoxetine failed to diminish the elevated expression of JAK and JNK genes, while it significantly decreased the expression of STAT3 and TLR4 genes. CONCLUSION: The findings revealed that fluoxetine has anti-inflammatory properties, mainly due to the reduction of inflammatory cytokines and inhibition of JAK/STAT3 and TLR4/JNK gene expression in macrophages.
Fluoxetine , Tumor Necrosis Factor-alpha , Animals , Mice , Rats , Cytokines/metabolism , Fluoxetine/pharmacology , Gene Expression , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Inflammation Mediators , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
OBJECTIVE: Breast cancer is the leading cause of death among women in many countries. Numerous factors serve as oncogenes or tumor suppressors in breast cancer. The large family of Tripartite-motif (TRIM) proteins with ~ 80 members has drawn attention for their role in cancer. TRIM3 and TRIM16 have shown suppressive activity in different cancers. This study aimed to evaluate the expression of TRIM3 and TRIM16 in cancerous and normal breast samples and to investigate their association with different clinical and pathological parameters. RESULTS: qRT-PCR was utilized to determine the gene expression of TRIM3 and TRIM16. The expression of TRIM3 and TRIM16 genes in tumor samples were significantly reduced to 0.45 and 0.29 fold, respectively. TRIM3 and TRIM16 genes expression were both positively correlated with the invasion of breast cancer. TRIM3 gene expression was associated with tumors' histological grade. However, no significant association was found between the expression of the genes and tumor size, stage and necrosis. The expression of TRIM3 and TRIM16 are significantly reduced in breast cancer tissues. Besides, the expression of both TRIM3 and TRIM16 genes significantly plummet in lymphatic/vascular and perineural invasive samples. Hence, we suggest a potential tumor suppressor role for TRIM3 and TRIM16 in breast cancer.
Breast Neoplasms , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Line, Tumor , Female , Humans , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/genetics
Objectives: Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis. Due to the beneficial effects of mesenchymal stem cells (MSCs) therapy on anxiety, an extreme and early manifestation of SAE, we hypothesized that MSCs-derived conditioned medium (CM) may be able to attenuate anxiety in cecal ligation and puncture (CLP)-induced sepsis. Materials and Methods: Rats were assigned into 4 groups: sham, CLP, MSC, and CM. All animals, except in the sham group, underwent the CLP procedure to induce sepsis. Two hours after sepsis induction, the rats in MSC and CM groups, received 1×106 MSCs and CM derived from the same number of cells, respectively. 48 hr after the treatments, anxiety-related behaviors were assessed, and brain and right hippocampal tissues were collected. Results: MSCs and CM enhanced the percentages of open arm entries and time spent in the open arms of the elevated plus-maze and the time spent in the light side of the light-dark box. MSCs and CM decreased the Evans blue content and decreased the IL-6 and TNF-α levels in the brain tissue samples. Reductions in the expression of 5-HT2A receptors and phosphorylation of ERK1/2 and an increase in the expression of 5-HT1A receptors in the hippocampal tissue samples were observed in the MSC and CM groups. Conclusion: MSCs and MSCs-derived CM attenuated anxiety-related behaviors to an equal extent by reducing inflammation, modifying 5-HT receptor expression changes, and inhibiting the ERK pathway. Therefore, MSCs-derived CM may be considered a promising therapy for comorbid anxiety in septic patients.
Background and Objectives: The virus SARS-CoV2, which causes COVID-19, affects the endocrine system. This study investigated serum concentrations of the thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in 53 outpatients infected with SARS-CoV2 and 53 non-infected matched participants in Khuzestan Province, Iran. We also examined the possible association of clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4. Materials and Methods: A checklist was applied to collect demographic and clinical data. Blood samples were taken for biochemical analysis of serum concentrations of TSH, T3, and T4. Clinical symptoms of the infected outpatients were monitored weekly for 28 days. Results: Our results indicated that, as the severity of the disease increased, the respiratory and pulse rates raised significantly. Additionally, disease severity was significantly different between genders. Specifically, 79.5% of the asymptomatic/mild, and 38.5% of moderate outpatients were men. We also found significantly lower serum T3 but higher T4 in infected outpatients, compared with controls. However, serum TSH did not significantly differ between the two groups. The generalized estimating equation (GEE) analysis revealed no relationship between clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4 in our study population. Additionally, GEE analysis showed that the odds ratio of neurological symptoms among women was 2.5 times that of men, the odds ratio of neurological symptoms in illiterates was 10 times higher than that of those without a high-school diploma, and the chance of developing pulmonary symptoms in those without high-school diploma was about 21 times higher than illiterates. Conclusion: In conclusion, this study showed that infected outpatients had significantly lower serum T3 but higher T4 than non-infected participants. There was no relation between symptom progression and disease severity with serum concentrations of TSH, T3, and T4, but educational status and sex significantly affected the chance of neurological and pulmonary symptoms occurring over 28 days. Our results may be used to develop potential therapies to treat COVID-19 disease.
COVID-19 , Hypothyroidism , Female , Humans , Iran/epidemiology , Male , Outpatients , RNA, Viral , SARS-CoV-2 , Thyrotropin , Thyroxine , Triiodothyronine
The antioxidant system can be critical in reducing exacerbated inflammation in COVID-19. This study compared the antioxidant and inflammatory responses between COVID-19 outpatients and seemingly healthy individuals. This descriptive-analytical cross-sectional study was conducted on 53 COVID-19 outpatients and 53 healthy individuals as controls. The serum concentrations of amyloid A (SAA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured and compared between COVID-19 patients and controls using the independent sample t-test before and after controlling for dietary supplement use. A generalized estimating equation (GEE) regression model, limited to COVID-19 patients, was used to evaluate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of disease symptoms on days 1, 7, 14, 21, and 28 after the disease onset. Serum concentrations of SOD (p ≤ 0.001) and GPx (p = 0.001) were significantly higher in COVID-19 patients than in controls before adjustment for dietary supplement use. GPx remained significantly higher among COVID-19 patients than in controls after adjustment for all dietary supplements (p = 0.005). Moreover, serum concentrations of GPx (p = 0.003), SOD (p = 0.022), and TAC (p = 0.028) remained significantly higher among COVID-19 patients than in controls after adjustment for vitamin D supplementation. This study showed higher GPx in COVID-19 outpatients than in controls after adjustment for dietary supplement use. Moreover, elevated SOD, GPx, and TAC concentrations were shown in COVID-19 outpatients compared to controls after adjusting for vitamin D supplementation. These results may provide a useful therapeutic target for treating oxidative stress in COVID-19 disease, which may help ameliorate the pandemic.
