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Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia.

J Infect Public Health 2021 Apr 24;14(7):832-838. Epub 2021 Apr 24.

King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients. Read More

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Impact of a pharmacist-led substance use disorder transitions of care clinic on postdischarge medication treatment retention.

J Subst Abuse Treat 2021 Apr 28;130:108440. Epub 2021 Apr 28.

VA Tennessee Valley Healthcare System, 1310 24th Avenue South, Nashville, TN 37212, United States.

Background: The Veterans Health Administration (VHA) has made significant improvements in increasing prescribing of medication treatment for opioid use disorder (MOUD) and medication treatment for alcohol use disorder (MAUD); however, several barriers to treatment retention remain. In an effort to improve MOUD/MAUD retention, a Veterans Affairs (VA) facility established a pharmacist-led substance use disorder (SUD) transitions of care telephone clinic for patients discharged from an inpatient hospitalization on MOUD/MAUD, including buprenorphine/naloxone (BUP/NAL) and extended-release (ER) naltrexone injections. Pharmacists within the clinic assess aspects of treatment retention such as medication tolerability, perceived barriers to continuing treatment, status of current prescriptions, and appointment coordination. Read More

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Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren's syndrome.

Autoimmun Rev 2021 Jun 9:102867. Epub 2021 Jun 9.

Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address:

Relevant reviews highlight the association between dysfunctional mitochondria and inflammation, but few studies address the contribution of mitochondria and mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) to cellular homeostasis and inflammatory signaling. The present review outlines the important role of mitochondria in cellular homeostasis and how dysfunctional mitochondrion can release and misplace mitochondrial components (cardiolipin, mitochondrial DNA (mtDNA), and mitochondrial formylated peptides) through multiple mechanisms. These components can act as damage-associated molecular patterns (DAMPs) and induce an inflammatory response via pattern recognition receptors (PRRs). Read More

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Light chain subunit of a poorly soluble human IgG2λ crystallizes in physiological pH environment both in cellulo and in vitro.

Biochim Biophys Acta Mol Cell Res 2021 Jun 9:119078. Epub 2021 Jun 9.

Department of Therapeutic Discovery, Amgen Inc., Thousand Oaks, CA 91320, USA.

Prominent inclusion bodies can develop in the endoplasmic reticulum (ER) when overexpressed antibodies possess intrinsically high condensation propensities. These observations suggest that antibodies deemed to show notable solubility problems may reveal such characteristics preemptively in the form of ER-associated inclusion bodies during antibody overexpression. To define the relationships between solubility problems and inclusion body phenotypes, we investigated the biosynthesis of a model human IgG2λ that shows severe opalescence in an acidic formulation buffer yet retains high solubility at physiological pH. Read More

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Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4.

J Lipid Res 2021 Jun 9:100091. Epub 2021 Jun 9.

Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Plasma LDL is produced from catabolism of VLDL and is cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL cholesterol levels. Circulating PCSK9 is mainly secreted by the liver, while VLDL is exclusively secreted by hepatocytes. Read More

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Molecular basis of anticoagulant and anti-complement activity of the tick salivary protein Salp14 and its homologues.

J Biol Chem 2021 Jun 9:100865. Epub 2021 Jun 9.

Department of Biochemistry, University of Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. Electronic address:

During feeding, a tick's mouthpart penetrates the host's skin and damages tissues and small blood vessels, triggering the extrinsic coagulation and lectin complement pathways. To elude these defense mechanisms, ticks secrete multiple anticoagulant proteins and complement system inhibitors in their saliva. Here we characterized the inhibitory activities of the homologous tick salivary proteins TSLPI, Salp14, and Salp9Pac from Ixodida scapularis in the coagulation cascade and the lectin complement pathway. Read More

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Nurse turnover: A longitudinal survival analysis of the Korea Nurses' Health Study.

J Adv Nurs 2021 Jun 12. Epub 2021 Jun 12.

College of Nursing, University of Illinois at Chicago, Chicago, IL, USA.

Aims: To identify factors influencing turnover among Korean female nurses from a longitudinal perspective.

Design: A national cohort study called the Korea Nurses' Health Study (2013-2020) was used.

Methods: A national sample of female nurses from module 1 (N = 20,613, 2013-2014), module 5 (N = 11,527, 2016-2017), module 7 (N = 8,658, 2018-2019) and module 8 (N = 10,253, 2019-2020) was used. Read More

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Split Green Fluorescent Protein-Based Contact Site Sensor (SPLICS ) for Heterotypic Organelle Juxtaposition as Applied to ER -Mitochondria Proximities.

Methods Mol Biol 2021 ;2275:363-378

Department of Biology, University of Padua, Padova, Italy.

In the last decades, membrane contact sites (MCSs) have been the object of intense investigation in different fields of cell physiology and pathology and their importance for the correct functioning of the cell is now widely recognized. MCS between any known intercellular organelles, including endoplasmic reticulum (ER), mitochondria, Golgi, endosomes, peroxisomes, lysosomes, lipid droplets, and the plasma membrane (PM), have been largely documented and in some cases the molecules responsible for the tethering also identified. They represent specific membrane hubs where a tightly coordinated exchange of ions, lipids, nutrients, and factors required to maintain proper cellular homeostasis takes place. Read More

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January 2021

Endoplasmic reticulum stress in the acute intestinal epithelial injury of necrotizing enterocolitis.

Pediatr Surg Int 2021 Jun 12. Epub 2021 Jun 12.

Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, 1526-555 University Ave, Toronto, ON, M5G 1X8, Canada.

Endoplasmic reticulum (ER) is a dynamic organelle that has many functions including protein synthesis, lipid synthesis, and calcium metabolism. Any perturbation in the ER such as accumulation of unfolded or misfolded proteins in the ER lumen causes ER stress. ER stress has been implicated in many intestinal inflammatory diseases. Read More

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Establishment of risk prediction nomogram for ipsilateral axillary lymph node metastasis in T1 breast cancer.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Feb;50(1):81-89

Department of Breast Surgery,Zhejiang University Lishui Hospital,Lishui 323000,Zhejiang Province,China.

:To establish and verify a risk prediction nomogram for ipsilateral axillary lymph node metastasis in breast cancer stage T1 (mass ≤ 2 cm). :The clinicopathological data of 907 patients with T1 breast cancer who underwent surgical treatment from January 2010 to June 2015 were collected,including 573 cases from the Second Affiliated Hospital of Zhejiang University School of Medicine (modeling group) and 334 cases from Zhejiang University Lishui Hospital (verification group). The risk factors of ipsilateral axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression. Read More

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February 2021

The immunity-malignancy equilibrium in multiple myeloma: lessons from oncogenic events in plasma cells.

FEBS J 2021 Jun 12. Epub 2021 Jun 12.

Age related Diseases Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.

Multiple myeloma is a malignancy of plasma cells that grow within the bone marrow and maintain massive immunoglobulin production. Disease evolution is driven by genetic lesions, whose effects on cell biology and fitness underlie addictions and vulnerabilities of myeloma cells. Several genes mutated in myeloma are strictly involved in dictating plasma cell identity and antibody factory function. Read More

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Co-expression of transcription factor AP-2beta (TFAP2B) and GATA3 in human mammary epithelial cells with intense, apicobasal immunoreactivity for CK8/18.

J Mol Histol 2021 Jun 11. Epub 2021 Jun 11.

Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

AP-2β is a new mammary epithelial differentiation marker and its expression is preferentially retained and enhanced in lobular carcinoma in situ and invasive lobular breast cancer. In normal breast epithelium AP-2β is expressed in a scattered subpopulation of luminal cells. So far, these cells have not been further characterized. Read More

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Maximum slope using ultrafast breast DCE-MRI at 1.5 Tesla: a potential tool for predicting breast lesion aggressiveness.

Eur Radiol 2021 Jun 11. Epub 2021 Jun 11.

Department of Radiology, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54 519, Vandoeuvre-les-Nancy, France.

Objectives: We evaluated the relationship between the maximum slope (MS) based on ultrafast breast DCE-MRI sequences, and the clinical parameters and routine prognostic factors of breast cancer.

Methods: 210 lesions were retrospectively evaluated: 150 malignant (30 each of luminal A invasive carcinoma, luminal B invasive carcinoma, HER2 overexpression (HER2), triple negative (TN), invasive lobular carcinoma (ILC)), and 60 benign. For each lesion, the MS was obtained with an ultrafast sequence and semi-quantitative curves were classified into three types with a conventional DCE sequence. Read More

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Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients.

NPJ Breast Cancer 2021 Jun 11;7(1):77. Epub 2021 Jun 11.

Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.

Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. Read More

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Neutrophil extracellular traps impair intestinal barrier functions in sepsis by regulating TLR9-mediated endoplasmic reticulum stress pathway.

Cell Death Dis 2021 Jun 11;12(6):606. Epub 2021 Jun 11.

Division of Trauma and Surgical Intensive Care Unit, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, P. R. China.

Increased neutrophil extracellular traps (NETs) formation has been found to be associated with intestinal inflammation, and it has been reported that NETs may drive the progression of gut dysregulation in sepsis. However, the biological function and regulation of NETs in sepsis-induced intestinal barrier dysfunction are not yet fully understood. First, we found that both circulating biomarkers of NETs and local NETs infiltration in the intestine were significantly increased and had positive correlations with markers of enterocyte injury in abdominal sepsis patients. Read More

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Targeting glucose metabolism sensitizes pancreatic cancer to MEK inhibition.

Cancer Res 2021 Jun 11. Epub 2021 Jun 11.

Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Read More

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Mass spectrometry imaging of L-[ring-C]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma.

Cancer Metab 2021 Jun 11;9(1):26. Epub 2021 Jun 11.

Maastricht MultiModal Molecular Imaging institute (M4I), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.

Background: Metabolic reprogramming is a common phenomenon in tumorigenesis and tumor progression. Amino acids are important mediators in cancer metabolism, and their kinetics in tumor tissue are far from being understood completely. Mass spectrometry imaging is capable to spatiotemporally trace important endogenous metabolites in biological tissue specimens. Read More

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The miR-200-Zeb1 axis regulates key aspects of β-cell function and survival in vivo.

Mol Metab 2021 Jun 8:101267. Epub 2021 Jun 8.

Institute of Molecular Health Sciences (IMHS), ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland; Competence Center Personalized Medicine, ETH Zurich, Voltastrasse 24, 8044 Zurich, Switzerland; Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. Electronic address:

Objective: The miR-200-Zeb1 axis regulates the epithelial-to-mesenchymal transition (EMT), differentiation, and resistance to apoptosis. A better understanding of these processes in diabetes is highly relevant as β-cell dedifferentiation and apoptosis contribute to loss of functional β-cell mass and diabetes progression, while EMT promotes loss of β-cell identity in in vitro expansion of human islets. While the miR-200 family has previously been identified as a regulator of β-cell apoptosis in vivo, studies focusing on Zeb1 are lacking. Read More

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A role for the Cockayne Syndrome B (CSB)-Elongin ubiquitin ligase complex in signal-dependent RNA polymerase II transcription.

J Biol Chem 2021 Jun 8:100862. Epub 2021 Jun 8.

Stowers Institute for Medical Research, Kansas City, MO 64110; Department of Biochemistry & Molecular Biology, University of Kansas Medical Center. Electronic address:

The Elongin complex was originally identified as an RNA polymerase II (RNAPII) elongation factor and subsequently as the substrate recognition component of a Cullin-RING E3 ubiquitin ligase. More recent evidence indicates the Elongin ubiquitin ligase assembles with the Cockayne syndrome B helicase (CSB) in response to DNA damage and can target stalled polymerases for ubiquitylation and removal from the genome. In this report, we present evidence that the CSB-Elongin ubiquitin ligase pathway has roles beyond the DNA damage response in the activation of RNAPII-mediated transcription. Read More

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Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress.

Eur J Pharmacol 2021 Jun 8:174247. Epub 2021 Jun 8.

Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit (BPRU), QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Office of Vice President for Research and Graduate Studies, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address:

Endoplasmic reticulum (ER) stress is an inflammatory response that contributes to endothelial dysfunction, a hallmark of cardiovascular diseases, in close interplay with oxidative stress. Recently, Sestrin2 (SESN2) emerged as a novel stress-inducible protein protecting cells from oxidative stress. We investigated here, for the first time, the impact of SESN2 suppression on oxidative stress and cell survival in human endothelial cells subjected to pharmacologically (thapsigargin)-induced ER stress and studied the underlying cellular pathways. Read More

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Effect of anti-hyperglycemic drugs on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells.

Eur J Pharmacol 2021 Jun 8:174249. Epub 2021 Jun 8.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL.

Endoplasmic reticulum (ER) stress plays a critical role in progression of diabetes and development of complications, notably cardiovascular disease. Some of the contemporary anti-hyperglycemic drugs have been shown to inhibit ER stress. To extend these observations, the effects of various anti-hyperglycemic agents were screened for their effects on ER stress. Read More

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Primary OA early joint degeneration induced by ER-stress is mitigated by resveratrol.

Am J Pathol 2021 Jun 8. Epub 2021 Jun 8.

Department of Pediatrics(,) The University of Texas Health Science Center at Houston (UTHealth), TX. Electronic address:

Given the increasing number of people living with OA, due to population aging and rising rates of obesity, there is an urgent need to identify effective treatment and preventions. Two top risk factors for OA, age and obesity, are associated with ER stress. The I-ERS mouse, an ER stress driven model of primary OA, was developed to study the role of ER stress in primary OA susceptibility. Read More

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Aerosol-induced direct radiative forcing effects on terrestrial ecosystem carbon fluxes over China.

Environ Res 2021 Jun 8:111464. Epub 2021 Jun 8.

Department of Chemical and Biochemical Engineering, Iowa Technology Institute, University of Iowa, Iowa City, IA, USA. Electronic address:

Atmospheric aerosols can change vegetation photosynthesis through the effects of aerosols on radiation, which will affect the peak carbon dioxide emissions and carbon neutrality at global scales. In this study, we quantify the aerosol-induced direct radiation forcing (ADRF) in China from 2001 to 2014 based on the radiation flux simulation used by the Fu-Liou radiation transfer model under with-aerosols and no-aerosols scenarios. Using the radiation simulation results, we modify the atmospheric forcing datasets to drive Community Land Model 4. Read More

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Erbium, Chromium:Yttrium-Scandium-Gallium-Garnet Laser for Root Conditioning and Reduction of Postoperative Morbidity in the Treatment of Gingival Recession Defects: A Randomized Controlled Clinical Trial.

Photobiomodul Photomed Laser Surg 2021 Jun 11. Epub 2021 Jun 11.

Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, New York, USA.

This clinical trial evaluates the effect of erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) root surface biomodification and laser harvesting of de-epithelialized gingival graft (DGG) on root coverage clinical outcomes and postoperative morbidity, and compares this to the conventional blade-harvested DGG method without Er,Cr:YSGG root surface biomodification in treatment of Miller's class I, II gingival recessions (GR). The application of laser technology to enhance tooth root coverage clinical outcomes as well as the impact of laser on postoperative morbidity after harvesting autogenous soft tissue grafts requires further research. This study is a randomized, single-blinded controlled trial, including 24 volunteers with isolated GR defects. Read More

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Real-world safety and effectiveness of rivaroxaban using Japan-specific dosage during long-term follow-up in patients with atrial fibrillation: XAPASS.

PLoS One 2021 11;16(6):e0251325. Epub 2021 Jun 11.

Medical Affairs and Pharmacovigilance, Bayer Yakuhin, Ltd., Osaka, Japan.

Background: The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was designed to investigate safety and effectiveness during long-term follow-up of rivaroxaban treatment, using reduced doses compared with other global regions, in Japanese patients with non-valvular atrial fibrillation in real-world clinical practice.

Methods: In this prospective, open-label, single-arm, observational study, 11,308 patients with non-valvular atrial fibrillation newly prescribed rivaroxaban (15/10 mg once daily) at 1416 sites across Japan were enrolled and followed for a mean of 2.5 years. Read More

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The effect of different irrigation solutions and activation techniques on the expression of growth factors from dentine of extracted teeth.

Int Endod J 2021 Jun 11. Epub 2021 Jun 11.

Department of Biochemistry, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey.

Aim: To evaluate in a laboratory study the effect of different irrigation solutions and activation techniques on transforming growth factor (TGF-β1), insulin growth factor-1 (IGF-1), bone morphogenetic protein-7 (BMP-7) and vascular endothelial growth factor-A (VEGF-A) release levels from the dentine of extracted teeth.

Methodology: Seventy premolar teeth with single root and canal were used. The lengths of the root segments were standardized to 12 mm and the root canals were prepared up to size 100 with hand files. Read More

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Off-label reduced-dose apixaban does not reduce hemorrhagic risk in Taiwanese patients with nonvalvular atrial fibrillation: A retrospective, observational study.

Medicine (Baltimore) 2021 Jun;100(23):e26272

Department of Internal Medicine, Division of Cardiology, National Cheng Kung University Hospital.

Abstract: East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF. Read More

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Low recurrence rate after endoscopic resection in non-ampullary duodenal lesions: A 16-year single-center retrospective study.

Medicine (Baltimore) 2021 Jun;100(23):e26267

Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea.

Abstract: Endoscopic resection (ER) for non-ampullary duodenal lesions (NADLs) is technically more difficult than lesions of the stomach. However, endoscopic treatment of duodenal lesions has been increasingly performed in recent years. This study aimed to evaluate the efficacy and safety of ER for NADLs. Read More

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Variants translating reduced expression of the beta estrogen receptor gene were associated with increased carotid intima media thickness: A cross-sectional study in late postmenopausal women.

Medicine (Baltimore) 2021 Jun;100(23):e26216

Department of Pediatrics, Obstetrics and Gynecology, University of Valencia and Service of Obstetrics and Gynecology, INCLIVA, Av Menéndez y Pelayo, Valencia, Spain.

Abstract: There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and β have not been investigated. Read More

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Resveratrol and endoplasmic reticulum stress: A review of the potential protective mechanisms of the polyphenol.

Phytother Res 2021 Jun 11. Epub 2021 Jun 11.

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

The endoplasmic reticulum (ER) is an organelle that performs a set of essential functions in cellular biology. These include synthesis of lipids, homeostasis of calcium, and controlling the folding of proteins. Inflammation and oxidative stress are two important reasons behind the accumulation of misfolded or unfolded proteins in the ER. Read More

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