Shahid Beheshti University of Medical Sciences and Health Services

About: Shahid Beheshti University of Medical Sciences and Health Services is a education organization based out in Tehran, Iran. It is known for research contribution in the topics: Population & Medicine. The organization has 19456 authors who have published 33659 publications receiving 365676 citations.

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

Abstract: Importance Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures Demographic and clinical factors. Main Outcomes and Measures Incident eGFR of less than 60 mL/min/1.73 m2. Results Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway.

Abstract: Here, we have investigated the effect of metformin pretreatment in the rat models of global cerebral ischemia. Cerebral ischemia which leads to brain dysfunction is one of the main causes of neurodegeneration and death worldwide. Metformin is used in clinical drug therapy protocols of diabetes. It is suggested that metformin protects cells under hypoxia and ischemia in non-neuronal contexts. Protective effects of metformin may be modulated via activating the AMP activated protein kinase (AMPK). Our results showed that induction of 30 min global cerebral I/R injury using 4-vesseles occlusion model led to significant cell death in the rat brain. Metformin pretreatment (200 mg kg/once/day, p.o., 2 weeks) attenuated apoptotic cell death and induced mitochondrial biogenesis proteins in the ischemic rats, analyzed using histological and Western blot assays. Besides, inhibition of AMPK by compound c showed that metformin resulted in apoptosis attenuation via AMPK activation. Interestingly, AMPK activation was also involved in the induction of mitochondrial biogenesis proteins using metformin, inhibition of AMPK by compound c reversed such effect, further supporting the role of AMPK upstream of mitochondrial biogenesis proteins. In summary, Metformin pretreatment is able to modulate mitochondrial biogenesis and apoptotic cell death pathways through AMPK activation in the context of global cerebral ischemia, conducting the outcome towards neuroprotection.

Metal-organic framework Uio-66 for adsorption of methylene blue dye from aqueous solutions

Abstract: Methylene blue color is a cationic dye which is used in textile industry. Health effects of methylene blue dye discharge into the environment is including toxicity, high color, reduced light penetration in water, high stability, and low degradation capability. So, removing it from the environment is extremely important. The aim of this study was to synthesize Uio-66 MOFs used for adsorption of methylene blue from synthetic sample. The synthesized UiO-66 MOFs were characterized by using XRD, FE-SEM, EDAX, and BET analyses. Various parameters were evaluated such as pH, initial MB concentration, reaction time, and adsorbent dose. The findings showed that the sizes of Uio-66 crystals were between 153 and 213 nm. Total pore volume, BET, and Langmuir surface area were found to be 657, 906 m2 g−1, and 0.446 m3 g−1, respectively. Zeta potential of Uio-66 was equal to 6. As a result, at higher than zeta potential point, methylene blue adsorption on Uio-66 is favorable. Maximum adsorption has been achieved at the pH = 9. The maximum adsorption capacity of Uio-66 for methylene blue was 91 mg/g. Optimum dose of Uio-66 was 0.4 g L−1 for methylene adsorption. The Langmuir I isotherm was a fit model to describe the adsorption isotherm. Pseudo-first-order kinetic model was a fit model to describe the adsorption kinetic of MB on Uio-66. The Uio-66 MOF is a promising adsorbent in the adsorption of methylene blue from aqueous solution.

Natural Products and Synthetic Analogs as a Source of Antitumor Drugs.

Abstract: Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs.

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury.

Abstract: Nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage after traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor, confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, intraperitoneally) or saline was administration at 1 and 3 h post-TBI. Animals were tested for neurological function and then sacrificed at 24 or 72 h post-TBI. Immunoblotting and histological analysis were performed to identify markers of NLRP3 inflammasome and proapoptotic activity in pericontusional areas of the brains at 24 or 72 h post-TBI. MCC950 treatment provided a significant improvement in neurological function and reduced cerebral edema in TBI animals. TBI upregulated NLRP3, apoptosis-associated speck-like adapter protein (ASC), cleaved caspase-1, and interlukein-1β (IL-1β) in the perilesional area. MCC950 efficiently repressed caspase-1 and IL-1β with a transient effect on ASC and NLRP3 post-TBI. MCC950 treatment also provided protection against proapoptotic activation of poly (ADP-ribose) polymerase and caspase-3 associated with TBI. A concurrent inhibition of inflammasome priming was also detectable at the nuclear factor kappa B/p65 and caspase-1 level. Our findings support the implication of NLRP3 inflammasome in the pathogenesis of TBI and further suggests the therapeutic potential of MCC950.