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Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling
Among the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, we discuss regulation of lncRNAs by anti-cancer drugs and genetic tools as well as the role of these factors in therapy response of lung cancer cells. © 202
Effects of Raspberry Fruit (Rubus anatolicus (focke) foke ex hausskn) Hydroalcoholic Extract on Blood Glucose, Lipid Profile and Oxidative Stress Markers in Streptozotocin-diabetic Rats
Background and Objectives: Diabetes is one of the most common endocrine disorders worldwide. Rubus anatolicus is rich in polyphenolic compounds that can protect individual from various chronic diseases such as diabetes. This study was carried out to investigate effects of hydroalcoholic extract of raspberry fruit Rubus anatolicus (focke) on blood glucose levels, lipid profiles and oxidative stress markers in streptozotocin-induced diabetic rats. Materials & Methods: In this study, 32 male Wistar rats weighing 150�200 g were used. Diabetes was induced in rats using streptozotocin and diabetic animals were then treated with raspberry fruit hydroalcoholic extract for 14 days. Rats were anesthetized using xylazine and ketamine mixture and sacrificed. Then, whole blood samples were collected from the animal hearts to assess their serum glucose levels, lipid profiles and oxidative markers. The p-value < 0.05was considered as significant. Results: Results of the present study showed that raspberry fruit extracts significantly decreased serum glucose levels, triglycerides, cholesterol, low-density lipoproteins and malondialdehyde levels in diabetic rats, compared to the diabetic control rats (p < 0.05). Moreover, serum low-density lipoproteins level, total antioxidant capacity and superoxide dismutase activity significantly increased in diabetic rats, compared to diabetic control rats (p < 0.05). Conclusion: The present study showed that fruit extract raspberry included good effects on blood glucose levels, lipid profiles and oxidative stress conditions in diabetic rats. © 2022, National Nutrition and Food Technology Research Institute. All rights reserved
Electrostatic interaction assisted Ca-decorated C20 fullerene loaded to anti-inflammatory drugs to manage cardiovascular disease risk in rheumatoid arthritis patients
The adsorption process of sulfasalazine (SSZ), curcumin (CUR), and naproxen (NPX) on the outer surfaces of pure and Ca-decorated C20 fullerenes were evaluated in solvent (water) environment by CAM-B3LYP functional. Our calculation illustrates that CUR/Ca-C20 complex had a strong binding energy via covalent interaction, whilst SSZ//Ca-C20 and NPX//Ca-C20 complexes illustrates a weak binding energy via electrostatic interaction. Inhibition of proinflammatory cytokines like cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) are effective targets to reduce cardiovascular risk in rheumatoid arthritis disease. We assessed the inhibitory activities of sulfasalazine, curcumin, and naproxen-functionalized Ca-decorated C20 fullerenes in comparison with the pure sulfasalazine, curcumin, and naproxen against COX-2, TNF-α, and IL-1β using molecular docking. Analysis of molecular docking represents that the interaction of SSZ, CUR, and NPX with Ca-decorated C20 fullerenes can improve the inhibition of proinflammatory cytokines in comparison with the pure drugs. © 2022 Elsevier B.V
Comparison Between Hesperidin, Coumarin, and Deferoxamine Iron Chelation and Antioxidant Activity Against Excessive Iron in the Iron Overloaded Mice
Objective: Iron accumulation in the brain leads to the development of Alzheimer�s and Parkinson�s diseases. Nowadays, iron chelation therapy is the best way to decrease the side effects of iron and amyloid plaques accumulation. Iron chelators are commonly used for the treatment of Alzheimer�s disease. Previous studies have shown that natural products such as phenol and flavonoid compounds could chelate heavy metals. In the current study, we examined the iron chelation activity of hesperidin and coumarin on the brain tissue of iron-overloaded mice. Methods: 48 NMRI male mice were divided into eight groups (n = 6). Six groups were treated with iron dextran (100 mg/kg/day) four times a week for 6 weeks. After stopping the injections for a month, five groups of iron-overloaded mice were treated with hesperidin, coumarin, and desferal four times a week subsequent for four subsequent weeks. Finally, the mice were anesthetized, and blood samples were collected from the ventricle of the heart for subsequent examination. The brain tissues were isolated and fixed in the 4 paraformaldehyde solution for Perl�s staining. Results: The results show that hesperidin and coumarin could strongly chelate excessive iron from the serum and deposit iron from the brain tissue compared to desferal group. Catalase and super oxidase activity were decreased in the iron-overloaded group, but in the treated group by hesperidin and coumarin, the enzyme�s activity was increased significantly. Conclusion: Hesperidin and coumarin, as natural products, are powerful options to chelate iron ions and increase the activity of antioxidant enzymes. Copyright © 2022 Aalikhani, Safdari, Jahanshahi, Alikhani and Khalili
A systematic approach introduced novel targets in rectal cancer by considering miRNA/mRNA interactions in response to radiotherapy
Background: The discovery of miRNA/mRNA interactions in several biological samples prompted the researchers to explore new biomarkers in tumors. Objective: We aimed to investigate the interactions of miRNA/mRNA in response to radiotherapy in the plasma samples of rectal cancer patients. Methods: Five microarray datasets related to cancerous and non-cancerous individuals were first used to construct networks. The databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze pathway enrichment. The plasma samples were then collected from 55 patients with recently diagnosed rectal cancer and 10 healthy subjects. For radiotherapy courses, the patients have consecutively received 30 sessions of local radiation for six weeks. At last, the expression of selected genes and miRNAs was experimentally measured before and after radiotherapy by qPCR, and the protein levels of the target genes were measured by ELISA assay. We evaluated the therapeutic responses based on the tumor regression grade of the Dworak classification. Results: We identified 5 up-regulated and 5 down-regulated miRNAs and 8 up-regulated and 3 down-regulated genes of the databases. There was a significant increase in tumor suppressor miRNAs, including miR-101-3p, miR-145-5p, miR-26a-5p, miR-34a-5p, and a significant decrease in oncomiRs, including miR-221-3p and miR-17-5p, after radiotherapy compared to the pre-treatment. Moreover, the up-regulated miR-17-5p and miR-221-5p and the down-regulated miR-101-3p and miR-145-5p were directly related to rectal cancer through the interaction with the Wnt, RAS, PI3K, and TGF-β signaling pathways. An analysis of receiver operating characteristics showed that miRNAs 221, 17, and 23 were response-related in locally advanced rectal cancer patients. ConclusionS: It seems that monitoring the miRNA/mRNA interactions during radiotherapy can be an appropriate diagnostic tool to track the recovery process and respond to standard therapies. © 2022 - IOS Press. All rights reserved
Improvement of anti-inflammatory and anticancer activities of poly(lactic-co-glycolic acid)-sulfasalazine microparticle via density functional theory, molecular docking and ADMET analysis
In the present study, we assessed improvement of anti-inflammatory activity and drug delivery of sulfasalazine (SSZ) by the poly(lactic-co-glycolic acid), (PLGA), in H2O and dichloromethane (DCM) environments via density functional theory (DFT), ADMET, and molecular docking. Our calculated results based on binding energy and thermodynamic parameter represents that the interaction between SSZ and PLGA in Complex A via double hydrogen bonds is stronger in comparison with Complex B. The analysis of Ultraviolet�visible (UV�VIS) spectra proved the interaction of SSZ with PLGA by time-dependent density functional theory (TDDFT). Infrared (IR) spectra demonstrated that the structure of PLGA was shifted in the presence of the SSZ. The interaction of SSZ with PLGA leads to an increase in dipole moment and higher solubility with more negative Gibbs free solvation energy (�Gsolv) values and lowering of the energy gap (Eg). The obtained results by Molecular docking demonstrates that the interaction of SSZ via its carboxylate group with PLGA (complex A) had a strong interaction towards the binding pocket of the target and as a potential inhibitor of the COX-2, TNF-α, and IL-1 receptors at the binding site as compared with the complex B. © 2021 The Author
Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients
Common variable immunodeficiency (CVID) is a primary immunodeficiency disease with a heterogeneous genetic background. Lipopolysaccharide-responsive beige-like anchor (LRBA), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have important regulatory roles in the immune responses. Here, we have investigated the expression of LRBA and CTLA-4 proteins in CVID patients with at least one presentation of early-onset occurrence, autoimmunity, or enteropathy. In this study, 20 newly diagnosed CVID patients without infection only phenotype, and ten healthy individuals were enrolled. The expressions of LRBA and CTLA-4 proteins were assessed by western blotting and flow cytometry, respectively. The patients were divided into two groups of autoimmunity-positive (11 cases) and autoimmunity-negative (9 patients). LRBA and CTLA-4 expressions were significantly lower in autoimmune-positive patients than in healthy individuals (P = .03 and P = .03, respectively). Autoimmune-negative patients had lower expression of LRBA and CTLA-4 than the control group, although it was not significant. There was a positive correlation between the expressions of LRBA and CTLA-4 in both groups of patients (P < .05). Furthermore, the highest frequency of LRBA (85.7) and CTLA-4 (71.4) defects was detected in those with concomitant presence of autoimmunity, enteropathy, and early-onset occurrence. Concurrent presence of autoimmunity, enteropathy, and early-onset occurrence in CVID patients could be indicative of a lack of expression in LRBA and CTLA-4 proteins. This could be helpful in early diagnosis and initiation of appropriate treatment in these patients prior to genetic confirmation. © 2020 Taylor & Francis Group, LLC
Trend Investigation of Thermal Comfort in Different Climates of Iran in Past Decades
Regarding climatic diversity in Iran and the dependence of many outdoor activities (occupational, recreational, tourism attraction, etc.) on climatic conditions, this study conducted aiming to evaluate thermal comfort fluctuations in Iran. Thermal comfort fluctuations in different climates of Iran were investigated between 1985 and 2014 using recorded meteorological data in 40 synoptic stations. The Mann-Kendall test and Sen's Slope were used to analyse the changing trends of the Humidex and to determine the actual slope of a trend over time, respectively. In overall, the southern areas of Iran have the longest period with unfavourable and extremely unfavourable climatic conditions in this study. Conversely, in the northern half of Iran, especially in North West areas, the appropriate summer season provides the best climatic conditions for outdoor activities. © 2022 Mehdi Asghari et al., published by Sciendo
All-Cause and Cause-Specific Mortality in Middle-Aged Individuals with Positive HBsAg: Findings from a Prospective Cohort Study
BACKGROUND: While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort. METHODS: The Golestan Cohort Study includes 50045 individuals aged 40-75 residing in Iran's Golestan province, enrolled during 2004-2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant. RESULTS: The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio aHR=1.15, 95% CI: 1.06-1.24) and liver-related mortality risk (aHR=7.13; 5.19-9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients. CONCLUSION: HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers. 2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Interplay between PI3K/AKT pathway and heart disorders
The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as H2O2, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury. © 2022, The Author(s)