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Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial
Get PDFObjective: The aim of this study was to evaluate the effect of curcumin on body weight, glycemic control and serum lipids in women suffering from polycystic ovary syndrome (PCOS). Methods: The current randomized, double-blinded, placebo-controlled clinical trial was performed on 60 subjects with PCOS, aged 18�40 years old. Subjects were randomly allocated to take 500 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Glycemic control and serum lipids were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was evaluated. Results: Curcumin significantly decreased weight (�0.8 ± 0.9 vs. �0.2 ± 0.8 kg, P = 0.03) and BMI (�0.3 ± 0.4 vs. �0.1 ± 0.3 kg/m2, P = 0.03). Curcumin, compared with the placebo, significantly reduced fasting glucose (β �2.63 mg/dL; 95 CI, �4.21, �1.05; P = 0.002), serum insulin (β �1.16 μIU/mL; 95 CI, �2.12, �0.19; P = 0.02), insulin resistance (β �0.26; 95 CI, �0.48, �0.03; P = 0.02), and significantly increased insulin sensitivity (β 0.006; 95 CI, 0.001, 0.01; P = 0.02). In addition, taking curcumin was associated with a significant reduction in total cholesterol (β �15.86 mg/dL; 95 CI, �24.48, �7.24; P = 0.001), LDL-cholesterol (β �16.09 mg/dL; 95 CI, �25.11, �7.06; P = 0.001) and total-/HDL-cholesterol ratio (β �0.62; 95 CI, �0.93, �0.30; P < 0.001), and a significant increase in HDL-cholesterol levels (β 2.14 mg/dL; 95 CI, 0.36, 3.92; P = 0.01) compared with the placebo. Additionally, curcumin administration up-regulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03) and low-density lipoprotein receptor (LDLR) (P < 0.001) compared with the placebo. Conclusions: Overall, curcumin administration for 12 weeks to women with PCOS had beneficial effects on body weight, glycemic control, serum lipids except triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ and LDLR. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N50. © 2020 European Society for Clinical Nutrition and Metabolis
Engineered Tumor-Derived Extracellular Vesicles: Potentials in Cancer Immunotherapy
Get PDFExosomes are nano vesicles from the larger family named Extracellular Vesicle (EV)s which are released by various cells including tumor cells, mast cells, dendritic cells, B lymphocytes, neurons, adipocytes, endothelial cells, and epithelial cells. They are considerable messengers that can exchange proteins and genetic materials between the cells. Within the past decade, Tumor derived exosomes (TEX) have been emerged as important mediators in cancer initiation, progression and metastasis as well as host immune suppression and drug resistance. Although tumor derived exosomes consist of tumor antigens and several Heat Shock Proteins such as HSP70 and HSP90 to stimulate immune response against tumor cells, they contain inhibitory molecules like Fas ligand (Fas-L), Transforming Growth Factor Beta (TGF-β) and Prostaglandin E2 (PGE2) leading to decrease the cytotoxicity and establish immunosuppressive tumor microenvironment (TME). To bypass this problem and enhance immune response, some macromolecules such as miRNAs, HSPs and activatory ligands have been recognized as potent immune inducers that could be used as anti-tumor agents to construct a nano sized tumor vaccine. Here, we discussed emerging engineered exosomes as a novel therapeutic strategy and considered the associated challenges. © Copyright © 2020 Taghikhani, Farzaneh, Sharifzad, Mardpour, Ebrahimi and Hassan
Determination of the concentration of heavy metals and their assessment of related potential health risk for dry black teas in kashan, iran
No full textTea is one of the most popular beverages being widely used by all families, especially among Iranians. Thus, the presence of any contaminants in tea can be dangerous for the health of consumers. The present study aimed to evaluate the concentration of heavy metals and their potential health risk in the dry black teas available in Kashan shops. This cross-sectional study was carried out on 31 brands of dry black tea purchased randomly from shops in Kashan, Iran in 2019. After the preparation of samples, the concentration of some heavy metals was determined by ICP-OES (Inductively Coupled Plasma/Optical Emission Spectrophotometer)based on the procedure described in the Standard Method. The evaluation carcinogenic risk was performed using related formula. Based on results of this study, the mean concentration of Fe, Zn, Cu, Ni, Cr, Pb, As and Cd was 83.42, 21.47, 19.46, 4.04, 0.72, 0.66, 0.4 and 0.04 Mgkg-1 of dry black tea, respectively. According to their associated potential health risk assessment, THQ of some heavy metals including As, Cu, Cr, Ni, Pb, Fe, Zn and Cd was 0.064, 0.023, 0.011, 9.76�10-3, 9.11�10-3, 5.76�10-3, 3.46�10-3 and 1.88�10-3 Mgkg-1day-1 and HI was less than one (0.129). Regarding the findings, it can be concluded that, the concentration of Cu, Ni and Cr in all samples of dry black tea was compatible with the Iranian and WHO standard level, while for Cd, Pb, As, Zn and Fe in some samples were more than the Iranian and WHO standard level. In addition, risk assessment analysis indicated that the consumption of the studied black tea had no carcinogenic potential risk for consumers. © 2020, Islamic Azad University. All rights reserved
Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases
Get PDFSome antimicrobial peptides (AMPs) are produced in the vaginal innate immune system and play an important role in protecting this organ against pathogenic agents. Moreover, sexually transmitted diseases have become a major problem in human societies and are rapidly spreading. The emergence of antibiotic-resistant microbes (superbugs) can pose a major threat to human societies and cause rapid spread of these diseases. Finding new antimicrobial compounds to fight superbugs is therefore essential. It has been shown that AMPs have good potential to become new antibiotics. The most important AMPs in the vaginal innate immune system are defensins, secretory leucocyte protease inhibitors, calprotectin, lysozyme, lactoferrin and elafin, which play an important role in host defence against sexually transmitted infections, modulation of immune responses and anticancer activities. Some AMPs, such as LL-37, magainin 2 and nisin, show both spermicidal and antimicrobial effects in the vagina. In this summary, we will discuss vaginal AMPs and continue to address some of the challenges of using peptides to control pathogens that are effective in sexually transmitted diseases. © 2019 The Author(s
Prevalence of torque teno virus in healthy individuals and those infected with hepatitis C virus living in Yazd, Iran
Get PDFBackground: Torque teno virus (TTV) is a non-enveloped DNA virus that its role as a helper or causative agent in hepatitis is still unclear. TTV prevalence varies in different regions of the world. This study aimed to determine the prevalence of TTV in healthy individuals and those infected with hepatitis C virus (HCV) living in Yazd city, Iran. Methods: In this case-control study, 50 healthy subjects and 68 HCV-positive individuals who referred to Yazd hospitals participated in this study. TTV DNA in serum samples were detected by nested polymerase chain reaction (PCR) using specific primers of 5?-UTR and N22 regions. The genotypes of HCV and TTV were determined by sequencing method. Results: TTV-DNA was detected in 2 out of 50 (4?) healthy individuals and in 4 out of 68 (5.8?) HCV-positive persons. There was not a significant correlation between the prevalence of TTV and HCV infection. The most common TTV genotypes among HCV-positive individuals were 3, 17 and 13, respectively. There was not a significant association obtained between HCV genotypes and TTV genotypes. Conclusion: The prevalence of TTV in Yazd province was low compared with the other areas of Iran. The prevalence of TTV in HCV infected people was not significantly higher than its rate in uninfected individuals. © 2020 Caspian Journal of Internal Medicine. All rights reserved
Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis
Get PDFMicroRNAs or miRNAs are a component of the non-coding RNAs family which is engaged in many cellular functions such as cell proliferation, apoptosis, gene expression, signaling pathways, angiogenesis, and etc. Endometriosis is a malignant gynecologic disorder occurring in women before menopausal age. Pathogenesis of this illness is still a discussion subject between the scientists but in our knowledge, microRNAs can be one of the possible involved factors. The purpose of this paper is to investigate the role of apoptotic activities of miRNAs in endometriosis. Accumulative evidence has demonstrated the role of cell proliferation, apoptosis, and invasion in the progression of these diseases. In this review, we looked into the specific role of apoptosis and its related genes and pathways in endometriosis and tied to present an explanation of how miRNAs can affect endometriosis by their apoptotic activities. What we found is that a great extent of miRNAs is involved in this illness and they are responsible for repressing apoptosis and progression of the disease. As a result, miRNAs have two different usages in endometriosis: biomarkers and potential therapeutic targets. In this review we gathered a great amount of evidence to inquire into the role of micro RNAs in inducing apoptosis and how this mechanism can be exerted for therapeutic purposes for endometriosis. © 2020 The Author(s)
The effects of resveratrol intake on weight loss: a systematic review and meta-analysis of randomized controlled trials
No full textThis systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of resveratrol intake on weight loss. We searched the following databases until July 2018: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95 confidence intervals (95 CI). Out of 831 reports, 36 RCTs were eligible for including to our meta-analysis. The pooled results, using random-effects model showed that resveratrol supplementation significantly decreased body weight (SMD = �0.17; 95 CI, �0.33, �0.01; P=0.03; I2: 62.6), body mass index (BMI) (SMD = �0.20; 95 CI, �0.35, �0.05; P=0.01; I2: 60.6), fat mass (SMD = �0.32; 95 CI, �0.62, �0.03; P=0.03; I2: 77.9) and waist circumference (WC) (SMD = �0.42; 95 CI, �0.68, �0.16; P=0.001; I2: 75.2), and significantly increased lean mass (SMD=1.21; 95 CI, 0.75, 1.67; P<0.001; I2: 87.6). We found no significant effect of resveratrol administration on leptin (SMD = �0.20; 95 CI, �0.68, 0.27; P=0.40; I2: 85.3) and adiponectin levels (SMD=0.08; 95 CI, �0.39, 0.55; P=0.74; I2: 91.0). Resveratrol supplementation significantly decreased body weight in obese patients (SMD �0.43; 95 CI, �0.60, �0.26) compared with other diseases (SMD 0.02; 95 CI, �0.29, 0.33), and type 2 diabetes mellitus (SMD �0.17; 95 CI, �0.37, 0.02). Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels. © 2018, © 2018 Taylor & Francis Group, LLC
Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency
Get PDFBackground: Inducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)�like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte�associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition. Methods: A combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA. Results: Four novel ICOS mutations included homozygous c.323332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+ T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy. Conclusions: ICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation. © 2019, The Author(s)
Development and Evaluation of Novel Aptamers Specific for Human PD1 Using Hybrid Systematic Evolution of Ligands by Exponential Enrichment Approach
No full textBackground: Programmed cell death protein 1 (PD1; also known as CD279) is an inhibitory receptor on T lymphocytes interacting with PD1-ligand 1 and PD1-ligand 2 in the synapse of T cells and antigen presenting cells (APC) resulting in the suppression of T cell activity. Systematic evolution of ligands by exponential enrichment (SELEX) is a method for generating aptamers which can bind specifically to the target of interest. PD-1 antagonistic aptamers could introduce an attractive alternative over the antibody-based treatments due to the distinguished advantages of aptamers including small size and efficient tissue penetration, low cost, lack of immunogenicity, and ease of manufacturing. Methods: Here, we developed single-stranded DNA aptamers which bind specifically to the human extracellular domain of PD-1. We performed hybrid SELEX, a combination of targeting of recombinant proteins and cell membrane expressed PD1 to select and identify specific aptamers and for the first time, homology of aptamer sequences selected from protein and cell SELEX pool have been evaluated in this study. Results: C42�aptamer, one of the selected aptamers, could specifically bind to human PD1 with dissociation constant in the nanomolar range. Although the developed aptamer inhibited binding of PD1 to PD-L1 but it was not able to restore the cell proliferation and cytokine production of the CD8+ CD279+ T cells. Conclusion: Further studies are required to assess the therapeutic potential of C42 aptamer and other aptamers developed in this study. The introduced PD1 specific aptamers can be used for specific detection of PD1 in diagnostic assay such as immunohistochemistry and targeted drug delivery to PD+ T cells. © 2020, © 2020 Taylor & Francis Group, LLC
