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The therapeutic role of lactobacillus and montelukast in combination with metformin in diabetes mellitus complications through modulation of gut microbiota and suppression of oxidative stress.

Int Immunopharmacol 2021 May 12;96:107757. Epub 2021 May 12.

Pharmacology department, Faculty of pharmacy, Horus University-Egypt, New Damietta 34518, Egypt.

Male reproductive dysfunction is one of the overlooked findings of diabetes mellitus (DM) that deserves greater scientific attention. This study is designed to explore the therapeutic potential of metformin and montelukast, in combination with Lactobacillus, for modulation of intestinal flora and suppression of oxidative stress in testicular and liver damage in diabetic male rats. A DM model was induced by streptozotocin (STZ)which caused functional, biochemical, and inflammatory injuries to the testicular and liver tissues. Read More

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MFGE8 mitigates brain injury in a rat model of SAH by maintaining vascular endothelial integrity via TIGβ5/PI3K/CXCL12 signaling.

Exp Brain Res 2021 May 15. Epub 2021 May 15.

Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52 Meihuadong Road, Zhuhai, 519000, Guangdong, China.

Leaked blood components, injured endothelial cells, local inflammatory response and vasospasm may converge to promote microthrombosis following subarachnoid hemorrhage (SAH). Previously, we showed that the milk fat globule-epidermal growth factor 8 (MFGE8) can mitigate SAH-induced microthrombosis. This present study was aimed to explore the molecular pathway participated in MFGE8-dependent protection on vascular endothelium. Read More

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Genetic Determinants of Paget's Disease of Bone.

Curr Osteoporos Rep 2021 May 14. Epub 2021 May 14.

Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.

Purpose Of Review: To provide an overview of the role of genes and loci that predispose to Paget's disease of bone and related disorders.

Recent Findings: Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget's disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. Read More

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The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study.

Panminerva Med 2021 May 14. Epub 2021 May 14.

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Background: the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study is a prospective registry of morbidity and mortality in initially untreated patients with essential hypertension whose initial diagnostic evaluation included 24-hour ambulatory blood pressure monitoring according to a standardized protocol. The present article summarizes the main results of the PIUMA study.

Methods: the PIUMA study is conducted in three Hospitals in Umbria, Central Italy. Read More

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Economic damage cost of premature death due to fine particulate matter in Seoul, Korea.

Environ Sci Pollut Res Int 2021 May 14. Epub 2021 May 14.

Institute for Environmental Research, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.

Analyzing the economic value of the damage to human health caused by environmental risks has become an essential research focus, given the increasing necessity for effective decision-making. Since logical and rational analyses such as cost-benefit and cost-utility analyses will likely gain importance in future policymaking, the evaluation of economic costs becomes necessary. Among the various types of air pollutants, fine particulate matter (PM) is reported as closely related to mortality. Read More

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Assessment of causality between climate variables and production for whole crop maize using structural equation modeling.

J Anim Sci Technol 2021 Mar 31;63(2):339-353. Epub 2021 Mar 31.

Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea.

This study aimed to assess the causality of different climate variables on the production of whole crop maize ( L.; WCM) in the central inland region of the Korea. Furthermore, the effect of these climate variables was also determined by looking at direct and indirect pathways during the stages before and after silking. Read More

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Adenosine A3 receptor activated in HO oxidative stress of primary open-angle glaucoma.

Ann Transl Med 2021 Apr;9(7):526

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.

Background: Primary open-angle glaucoma (POAG), as one of the leading reasons for blindness, is mainly due to trabecular meshwork (TM) dysfunction. Bioinformatics analysis was used to find related genes involved in TM oxidative stress, which is a major cause of TM fibrosis.

Methods: A total of three datasets from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs). Read More

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Case Report: First Two Identified Cases of Fabry Disease in Central Asia.

Front Genet 2021 27;12:657824. Epub 2021 Apr 27.

Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia.

Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked inherited, genetic disease due to the functional deficiency of lysosomal α-galactosidase (α-GAL) that leads to the accumulation of glycosphingolipids (mainly globotriaosylceramide or Gb) and its derivative globotriaosylsphingosine or lyso-Gb. Classic FD is a multisystem disorder which initially presents in childhood with neuropathic pain and dermatological, gastrointestinal, ocular, and cochleo-vestibular manifestations. Over time, end-organ damage such as renal failure, cardiac arrhythmia and early stroke may develop leading to reduced life expectancy in the absence of specific treatment. Read More

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A Palmitoylethanolamide Producing Improves Toxin A-Induced Colitis.

Front Pharmacol 2021 27;12:639728. Epub 2021 Apr 27.

Department of Clinical Medicine and Surgery, Section of Gastroenterology, University Federico II, Naples, Italy.

Genetically engineered probiotics, able to deliver therapeutically active compounds while restoring gut , could represent an attractive therapeutic alternative in infection (CDI). Palmitoylethanolamide is an endogenous lipid able to exert immunomodulatory activities and restore epithelial barrier integrity in human models of colitis, by binding the peroxisome proliferator-activated receptor-α (PPARα). The aim of this study was to explore the efficacy of a newly designed PEA-producing probiotic (pNAPE-LP) in a mice model of toxin A (TcdA)-induced colitis. Read More

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Cyclic oligoadenylate signalling and regulation by ring nucleases during type III CRISPR defence.

RNA 2021 May 13. Epub 2021 May 13.

University of St Andrews.

In prokaryotes, CRISPR-Cas immune systems recognise and cleave foreign nucleic acids to defend against Mobile Genetic Elements (MGEs). Type III CRISPR-Cas complexes also synthesise cyclic oligoadenylate (cOA) second messengers, which activate CRISPR ancillary proteins involved in antiviral defence. In particular, cOA-stimulated nucleases degrade RNA and DNA non-specifically, which slows MGE replication but also impedes cell growth, necessitating mechanisms to eliminate cOA in order to mitigate collateral damage. Read More

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Deep-inspirational breath-hold (DIBH) technique in left-sided breast cancer: various aspects of clinical utility.

Radiat Oncol 2021 May 13;16(1):89. Epub 2021 May 13.

Department of Oncotherapy, University of Szeged, Korányi fasor 12, 6720, Szeged, Hungary.

Background: Studying the clinical utility of deep-inspirational breath-hold (DIBH) in left breast cancer radiotherapy (RT) was aimed at focusing on dosimetry and feasibility aspects.

Methods: In this prospective trial all enrolled patients went through planning CT in supine position under both DIBH and free breathing (FB); in whole breast irradiation (WBI) cases prone CT was also taken. In 3-dimensional conformal radiotherapy (3DCRT) plans heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast doses were analyzed. Read More

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Organ and tissue-specific distribution of selected polycyclic aromatic hydrocarbons (PAHs) in ApoE-KO mouse.

Environ Pollut 2021 Apr 24;286:117219. Epub 2021 Apr 24.

State Key Laboratory of Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, China. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants resulting from the incomplete combustion of hydrocarbons. Exposure to PAHs is implicated in the pathogenesis of the cardiovascular disease, pulmonary disease, and even cancer. However, little is known about organ- and tissue-specific distribution patterns of PAHs in animals at macro-tissue and microscopic levels. Read More

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Anabolic-androgenic steroids impair mitochondrial function and redox status in the heart and liver of mice.

Steroids 2021 May 10:108861. Epub 2021 May 10.

Laboratory of Neurotrauma and Biomarkers, PPG-Ciências Biológicas Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brasil. Electronic address:

Supraphysiological doses of anabolic-androgenic steroids (AAS) may cause long-term functional abnormalities, particularly in the heart and liver, which may only represent the later-stage of the cumulative damage caused by dysfunctional organelles. We investigated whether mid-term supraphysiological doses of Testosterone and Nandrolone impair mitochondrial Ca and membrane potential (ΔΨm) dynamics, and redox machinery in the heart and liver of mice. CF1 albino mice were treated daily with 15 mg/kg of Nandrolone (ND) or Testosterone (T), or oil (vehicle) for 19 days. Read More

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The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete.

PLoS Pathog 2021 May 13;17(5):e1009546. Epub 2021 May 13.

Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, United States of America.

The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Read More

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NOXA-mediated degradation of MCL1 and BCL2L1 causes apoptosis of daunorubicin-treated human acute myeloid leukemia cells.

J Cell Physiol 2021 May 13. Epub 2021 May 13.

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.

Daunorubicin (DNR) is used clinically to treat acute myeloid leukemia (AML), while the signaling pathways associated with its cytotoxicity are not fully elucidated. Thus, we investigated the DNR-induced death pathway in the human AML cell lines U937 and HL-60. DNR-induced apoptosis in U937 cells accompanied by downregulation of MCL1 and BCL2L1, upregulation of Phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), and mitochondrial depolarization. Read More

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Evaluation of the antimetastatic and anticancer activities of morin in HER2‑overexpressing breast cancer SK‑BR‑3 cells.

Oncol Rep 2021 Jul 13;46(1). Epub 2021 May 13.

Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk University, Gyeongju‑si, Gyeongsangbuk‑do 38066, Republic of Korea.

Morin (2',3,4',5,7‑pentahydroxyflavone), a flavonoid isolated from members of the Moraceae family and the leaves of Buread, is a well‑known natural substance with anti‑inflammatory, antioxidative, antimetastasis, and anticancer effects. However, its anticancer activity has not been comprehensively investigated in human epidermal growth factor receptor 2 (HER2)‑overexpressing breast cancer cells. Here, we evaluated the effects of morin on metastasis and cell viability in HER‑2‑overexpressing human breast cancer SK‑BR‑3 cells. Read More

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Ultrasmall Gd@Cdots as a radiosensitizing agent for non-small cell lung cancer.

Nanoscale 2021 May 13. Epub 2021 May 13.

Department of Chemistry, University of Georgia, 140 Cedar Street, Athens, GA 30602, USA.

High-Z nanoparticles (HZNPs) afford high cross-section for high energy radiation and have attracted wide attention as a novel type of radiosensitizer. However, conventional HZNPs are often associated with issues such as heavy metal toxicity, suboptimal pharmacokinetics, and low cellular uptake. Herein, we explore gadolinium-intercalated carbon dots (Gd@Cdots) as a dose-modifying agent for radiotherapy. Read More

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The Mechanism of Lavender Essential Oil in the Treatment of Acute Colitis Based on "Quantity-Effect" Weight Coefficient Network Pharmacology.

Front Pharmacol 2021 22;12:644140. Epub 2021 Apr 22.

Department of Pharmaceutics, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a "quantity-effect" weight coefficient. Online databases such as GeneCards and String were used to construct a "lavender essential oil compound target disease target" network to extract the key targets of core compounds acting on diseases. Read More

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Protein Kinase D-Dependent Downregulation Of Immediate Early Genes Through Class IIa Histone Deacetylases In Acute Lymphoblastic Leukemia.

Mol Cancer Res 2021 May 12. Epub 2021 May 12.

Pediatrics, Medicine and Biochemistry And Molecular Biology, University of Miami Miller School of Medicine

Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wide metabolic-stress regulated genes, we used RNA-Seq in ALL cells treated with AICAR, an AMPK activator. RNA-Seq identified the immediate early genes (IEGs) as a subset of genes downregulated by AICAR. Read More

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Setaria tundra, what do we know, what is still to be discovered?

Ann Parasitol 2021 ;667(1):1-10

Department of Parasitology, Faculty of Biology, Warsaw University, ul. Miecznikowa 1, 02-096 Warsaw, Poland.

Over the past years, the nematode species from the Onchocercidae family, Setaria tundra, has expanded its range by thousands of kilometres from subpolar to subtropical climate zone. Its presence has been confirmed in seven new countries. The appearance of this parasite in many other European countries, especially central and southern ones, is highly probable. Read More

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BRCC3 promotes activation of the NLRP6 inflammasome following cerebral ischemia/reperfusion (I/R) injury in rats.

Neurosci Lett 2021 May 9;756:135954. Epub 2021 May 9.

Department of Pathology, Chongqing Medical University, Chongqing, CQ, 400016, China. Electronic address:

NOD-like receptor family pyrin domain containing 6 (NLRP6), a novel member of the NLR family, has been confirmed to have an inflammasome-dependent proinflammatory effect in cerebral ischemia/reperfusion injury. NLRP6 assembles a multimeric inflammasome complex comprising the adaptor ASC and the effector pro-caspase-1 to mediate the activation of caspase-1. The molecular mechanism regulating activation of the NLRP6 inflammasome remains unclear. Read More

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Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells.

Immunity 2021 May 5. Epub 2021 May 5.

Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Program in Immunology, Harvard Medical School, Longwood Avenue, Boston, MA, USA. Electronic address:

Two sets of innate immune proteins detect pathogens. Pattern recognition receptors (PRRs) bind microbial products, whereas guard proteins detect virulence factor activities by the surveillance of homeostatic processes within cells. While PRRs are well known for their roles in many types of infections, the role of guard proteins in most infectious contexts remains less understood. Read More

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Identification of Key Genes and Pathways Associated with Hepatosplenic T-Cell Lymphoma (HSTCL) by Bioinformatics Analysis.

Clin Lab 2021 May;67(5)

Background: Prognosis of Hepatosplenic T-Cell Lymphoma (HSTCL) is very poor, while the molecular mechanism of this disease has rarely been investigated and remains mysterious. The aim of the study is to screen differentially expressed genes (DEGs) of patients with HSTCL and normal controls, explore the pathogenesis, and provide guidance for the gene diagnosis and precise treatment of HSTCL.

Methods: The genetic chip data GSE57520 of HSTCL was searched from the GEO database, and the quality control and DEGs screening were performed through BART online tools. Read More

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Repeated Remote Ischaemic Preconditioning Can Prevent Acute Mountain Sickness after Rapid Ascent to a High Altitude.

Eur J Sport Sci 2021 May 12:1-36. Epub 2021 May 12.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.

Background: Acute Mountain Sickness (AMS) is a syndrome with nonspecific neurological symptoms that can occur in unacclimatized persons after Rapid Ascent to a High Altitude. Since Repeated Remote Ischaemic Preconditioning (RIPC) can protect remote organs from subsequent hypoxic or ischaemic damage, the aim of the present study was to assess the effectiveness of 4 different RIPC protocols varying in duration and frequency for preventing AMS after Rapid Ascent to a High Altitude.

Methods: We designed a prospective but not blinded study in which we randomly divided participants into five groups. Read More

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The role of medications in successful aging.

R D Langer

Climacteric 2021 May 12:1-8. Epub 2021 May 12.

Jackson Hole Center for Preventive Medicine, Jackson, WY, USA.

Successful aging includes good health and low levels of disability. To that end, primary prevention is far better than managing subsequent organ damage. When medication is needed to prevent or manage disease, the preferred choice should be associated with the greatest benefits and fewest adverse effects. Read More

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Safety assessment of titanium dioxide (E171) as a food additive.

EFSA J 2021 May 6;19(5):e06585. Epub 2021 May 6.

The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. Read More

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Evaluation of outer nuclear layer overshadowed by retinal vessels in retinitis pigmentosa.

Eye (Lond) 2021 May 11. Epub 2021 May 11.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.

Objectives: We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images.

Methods: We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. Read More

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Acute toxicity analysis of an inhibitor of BCL2, Disarib, in rats.

Sci Rep 2021 May 11;11(1):9982. Epub 2021 May 11.

Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore, 560100, India.

Apoptosis or programmed cell death is a highly regulated process, which eliminates unwanted and damaged cells. Inhibition of apoptosis is a hallmark of cancer cells. BCL2 family proteins are known to play a vital role in the regulation of apoptosis. Read More

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Thalidomide reduces glycerol-induced acute kidney injury by inhibition of NF-κB, NLRP3 inflammasome, COX-2 and inflammatory cytokines.

Cytokine 2021 May 8:155574. Epub 2021 May 8.

Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address:

Acute kidney injury (AKI) is an important clinical complication of rhabdomyolysis. The inflammatory processes are involved in the pathogenesis of AKI induced by rhabdomyolysis. Thalidomide is an anti-inflammatory agent that has been used in the treatment of inflammatory disorders. Read More

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Effect of soil sulfamethoxazole on strawberry (Fragaria ananassa): Growth, health risks and silicon mitigation.

Environ Pollut 2021 May 7;286:117321. Epub 2021 May 7.

College of Horticulture Science and Engineering, Shandong Agricultural University, Taian, 271018, China; Collaborative Innovation Center of Fruit & Vegetable Quality and Efficient Production in Shandong Taian, 271018, China; Key Laboratory of Biology of Horticultural Crops in Huanghuai Region, Ministry of Agriculture and Rural Affairs, Taian, 271018, China; State Key Laboratory of Crop Biology, Taian, 271018, China. Electronic address:

The negative impact of antibiotic pollution on the agricultural system and human health is a hot issue in the world. However, little information is available on the antibiotics toxicity mechanism and the role of silicon (Si) to alleviate the antibiotics toxicity. In this study, strawberry (Fragaria ananassa) showed excitatory response to low-dose SMZ (1 mg L), but strawberry root and photosynthetic efficiency were damaged under high level. Read More

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