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Corticosterone in the dorsolateral striatum facilitates the extinction of stimulus-response memory.

Neurobiol Learn Mem 2021 Jun 21:107481. Epub 2021 Jun 21.

Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, Qro., México. Electronic address:

Glucocorticoid hormones are crucially involved in modulating mnemonic processing of stressful or emotionally arousing experiences. They are known to enhance the consolidation of new memories, including those that extinguish older memories. In this study, we investigated whether glucocorticoids facilitate the extinction of a striatum-dependent, and behaviorally more rigid, stimulus-response memory. Read More

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Digestive properties and effects of Chimonanthus nitens Oliv polysaccharides on antioxidant effects in vitro and in immunocompromised mice.

Int J Biol Macromol 2021 Jun 21. Epub 2021 Jun 21.

Key Lab for Agro-product Processing and Quality Control of Nanchang City, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China. Electronic address:

The study was aimed to investigate the simulated digestion behavior of the bioactive polysaccharides from Chimonanthus nitens Oliv (COP1), antioxidant activity in vitro, and prevention against cyclophosphamide (CP) induced oxidative damage in mice. The results showed that COP1 were 18.843 kDa, and consisted of arabinose (56. Read More

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Rapamycin alleviates memory deficit against pentylenetetrazole-induced neural toxicity in Wistar male rats.

Mol Biol Rep 2021 Jun 24. Epub 2021 Jun 24.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

Numerous studies have reported that epilepsy causes memory deficits. The present study was aimed at studying the effect of rapamycin against the memory deficiency of the pentylenetetrazole (PTZ)-kindled animal model of epilepsy. In the present experiment, we randomly chose thirty male rats from the species of Wistar and categorized them in groups of control and experiment (6 for each group). Read More

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Pulverizing medication as a harm reduction and intentional drug overdose prevention strategy: Two case studies.

Neuropsychopharmacol Rep 2021 Jun 24. Epub 2021 Jun 24.

Department of Psychiatry, KKR Sapporo Medical Center, Hokkaido, Japan.

Aims: We explored the use of pulverized medication as a new method to prevent intentional drug overdose.

Methods: This case study presents data obtained from the medical records of two female patients, aged 19 and 27 years, who presented with schizophrenia and neurodevelopmental disorder, respectively. Both patients provided written informed consent. Read More

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Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects.

PLoS One 2021 23;16(6):e0252597. Epub 2021 Jun 23.

Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, United States of America.

Wound healing is a multi-step process to rapidly restore the barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Read More

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3',4'-Dihydroxyflavonol (DiOHF) prevents DNA damage, lipid peroxidation and inflammation in ovarian ischaemia-reperfusion injury of rats.

J Obstet Gynaecol 2021 Jun 23:1-8. Epub 2021 Jun 23.

Department of Pathology, Meram Medical School, Necmettin Erbakan University, Konya, Turkey.

This study aimed to determine the effect of 3',4'-Dihydroxyflavonol (DiOHF) on lipid peroxidation, DNA damage and inflammation in ovarian ischaemia (I)-reperfusion (R) injury. This study was performed on 44 Wistar-albino female rats. Groups were designed as Control; Sham; I/R (the left ovary was ligated for 2 h and then reperfused for 2 h); I/R + DiOHF (after 2 h ischaemia and 2 h reperfusion, 30 mg/kg of DiOHF was given intraperitoneally and reperfusion was allowed for 2 h more); I + DiOHF + R (after 2 h I, 30 mg/kg of DiOHF was given at the beginning of 2 h reperfusion); DiOHF + I/R (2 h after DiOHF administration, the left ovary was ligated for 2 h and then reperfused for 2 h). Read More

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Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention.

medRxiv 2021 Jun 17. Epub 2021 Jun 17.

Background: Casirivimab and imdevimab (REGEN-COV™) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19. Here we explore the possibility that subcutaneous REGEN-COV prevents SARS-CoV-2 infection and subsequent Covid-19 in individuals at high risk of contracting SARS-CoV-2 by close exposure in a household with a documented SARS-CoV-2-infected individual.

Methods: Individuals ≥12 years were enrolled within 96 hours of a household contact being diagnosed with SARS-CoV-2 and randomized 1:1 to receive 1200 mg REGEN-COV or placebo via subcutaneous injection. Read More

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CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context.

Sci Rep 2021 Jun 21;11(1):12964. Epub 2021 Jun 21.

Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA, Córdoba, Argentina.

Preclinical models of stress-induced relapse to drug use have shown that the dysregulation of glutamatergic transmission within the nucleus accumbens (NA) contributes notably to the reinstatement of cocaine-seeking behavior in rodents. In this sense, there has been increasing interest in the cannabinoid type-1 receptor (CB1R), due to its crucial role in modulating glutamatergic neurotransmission within brain areas involved in drug-related behaviors. This study explored the involvement of CB1R within the NA subregions in the restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP), as well as in the regulation of glutamatergic transmission, by using a pharmacological approach and the in vivo microdialysis sampling technique in freely moving rats. Read More

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Monoclonal antibody directed to the PilQ -PilA DSL region in Pseudomonas aeruginosa improves survival of infected mice with antibiotic combination.

Microb Pathog 2021 Jun 18:105060. Epub 2021 Jun 18.

Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

The infections caused by Pseudomonas aeruginosa are related to high mortality and morbidity in critically ill patients because of multidrug resistance. Thus, we performed the efficacy of the monoclonal antibody (mAb) against PilQ -PilA DSL region (QA) in combination with antibiotics in a model of P. aeruginosa infection. Read More

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Effect of thymoquinone on high fat diet and STZ-induced experimental type 2 diabetes: A mechanistic insight by in vivo and in silico studies.

J Food Biochem 2021 Jun 21:e13807. Epub 2021 Jun 21.

Pharmaceutical Chemistry & Pharmacognosy Department, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia.

The aim was to investigate whether thymoquinone (TQ) attenuates hyperglycemia-induced insulin resistance in experimental type 2 diabetes. Type 2 diabetes mellitus (T2DM) was induced by injection of streptozotocin (STZ, 40 mg/kg) in high fat diet (HFD) rats. The levels of glucose, insulin, area under curve (AUC) of glucose, lipid profile parameters, homeostasis model assessment of insulin resistance (HOMA-IR), peroxisome proliferator-activated receptor-γ (PPARγ), and dipeptidyl peptidase peptidase-IV (DPP-IV) were evaluated in HFD + STZ-induced type 2 diabetic rats. Read More

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Quercetin with lycopene modulates enzymic antioxidant genes pathway in isoproterenol cardiotoxicity in rats.

Libyan J Med 2021 Dec;16(1):1943924

Department of Cardiology, Shandong Rongjun General Hospital, Jinan, Shandong Province, China.

Quercetin (QN) is a naturally occurring phenolic compound found largely in vegetables and fruits. Lycopene (LY) is yet another natural phytocompound, found abundantly in red-colored fruits and vegetables. Both have been reported to have beneficial activities in humans. Read More

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December 2021

Co-administration of obeticholic acid and simvastatin protects against high-fat diet-induced non-alcoholic steatohepatitis in mice.

Exp Ther Med 2021 Aug 3;22(2):830. Epub 2021 Jun 3.

The Key Laboratory of Hepatic Fibrosis Mechanisms of Chronic Liver Diseases in Hebei Province, Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.

Non-alcoholic steatohepatitis (NASH) has no approved therapy. The farnesoid X nuclear receptor (FXR) agonist obeticholic acid (OCA) has shown promise as a drug for NASH, but can adversely affect plasma lipid profiles. Therefore, the present study aimed to investigate the effects and underlying mechanisms of OCA in combination with simvastatin (SIM) in a high-fat diet (HFD)-induced model of NASH. Read More

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Maternal vitamin D administration attenuates metabolic disturbances induced by prenatal exposure to dexamethasone in a sex-dependent manner.

J Steroid Biochem Mol Biol 2021 Jun 17:105941. Epub 2021 Jun 17.

Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil. Electronic address:

Purpose: The overexposure to synthetic glucocorticoids (GC) during pregnancy can predispose to metabolic diseases during adulthood. Vitamin D is not only crucial for fetal development, but also exerts direct effects on the GC sensitivity and down-regulates GC receptors. Given the vitamin D effects on glucocorticoid-related parameters, we aimed to investigate a possible protective role of maternal vitamin D administration on the glucose homeostasis of rats exposed to dexamethasone in utero. Read More

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PepBiotics, novel cathelicidin-inspired antimicrobials to fight pulmonary bacterial infections.

Biochim Biophys Acta Gen Subj 2021 Jun 17:129951. Epub 2021 Jun 17.

Faculty of Veterinary Medicine, Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Section Molecular Host Defence, Utrecht University, the Netherlands.

Background: Antimicrobial peptides are considered potential alternatives for antibiotics. Here we describe the antibacterial properties of a family of novel cathelicidin-related (CR-) peptides, which we named PepBiotics, against bacteria typically present in cystic fibrosis (CF) patients.

Methods: Broth dilution assays were used to determine antibacterial activity of PepBiotics under physiological conditions, as well as development of bacterial resistance against these peptides. Read More

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The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain.

Eur J Pharmacol 2021 Jun 17;907:174267. Epub 2021 Jun 17.

Department of Anesthesiology and Perioperative Medicine, 900 Hospital of the Joint Logistic Support Force / Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, 350025, Fujian, PR China; Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, Fujian, PR China. Electronic address:

Ulinastatin is a broad-spectrum protease inhibitor widely used for the treatment of various inflammation-related diseases owing to its recognized excellent anti-inflammatory and cytoprotective properties. However, whether ulinastatin can relieve postoperative pain remains unclear. In this study, we evaluated the analgesic effects of ulinastatin administered either as a single agent or in combination with sufentanil in a validated preclinical rat model of postoperative pain induced by plantar incision. Read More

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Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals.

Sci Immunol 2021 06;6(60)

Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA.

The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Read More

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Inhibition of sphingosine 1-phosphate protects mice against chondrocyte catabolism and osteoarthritis.

Osteoarthritis Cartilage 2021 Jun 15. Epub 2021 Jun 15.

- Université de Paris, BIOSCAR Inserm U1132, F-75010 Paris, France; - Service de rhumatologie, AP-HP, Hôpital Lariboisière, F-75010 Paris, France. Electronic address:

Objective: Cartilage loss observed in osteoarthritis (OA) is prevented when osteoclasts in the subchondral bone are inhibited in mice. Here, we investigated the role of the osteoclast secretome and of the lipid mediator sphingosine 1-phosphate (S1P) in chondrocyte metabolism and OA.

Materials And Methods: We used SphK1 and wild type mice to assess the effect of murine osteoclast secretome in chondrocyte metabolism. Read More

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Gut Microbiota Composition Affects Procyanidin A2-Attenuated Atherosclerosis in ApoE Mice by Modulating the Bioavailability of Its Microbial Metabolites.

J Agric Food Chem 2021 Jun 18. Epub 2021 Jun 18.

Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.

Procyanidin A2 (PCA2) has been shown to improve lipid metabolism. However, it remains to know whether it can play a role in preventing atherosclerosis (AS) through gut microbiota. This study examined the effect of PCA2 on high fat diet (HFD)-induced AS in ApoE mice with an intact and antibiotic-depleted microbiota. Read More

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The investigation of the protective effect of water extract and vitamin E on malathion-induced oxidative damage in rats.

Toxicol Res (Camb) 2021 May 1;10(3):627-630. Epub 2021 Jun 1.

Faculty of Healthy Science, Department of Nursing, Giresun University, 28100, Giresun, Turkey.

Pesticides and other agricultural protective chemical products are widely used almost all over the world. It poses a serious threat, especially for public health. Many studies have reported that pesticide poisoning is a major problem in morbidity and mortality. Read More

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Nanoparticle-Mediated Lipid Metabolic Reprogramming of T Cells in Tumor Microenvironments for Immunometabolic Therapy.

Nanomicro Lett 2021 Jan 4;13(1):31. Epub 2021 Jan 4.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Highlights: aCD3/F/AN, anti-CD3e f(ab')2 fragment-modified and fenofibrate-encapsulated amphiphilic nanoparticle, reprogrammed mitochondrial lipid metabolism of T cells. aCD3/F/AN specifically activated T cells in glucose-deficient conditions mimicking tumor microenvironment, and exerted an effector killing effect against tumor cells. In vivo treatment with aCD3/F/AN increased T cell infiltration, cytokine production, and prevented tumor growth. Read More

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January 2021

The Combination Immunotherapy of TLR9 Agonist and OX40 Agonist via Intratumoural Injection for Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 8;8:529-543. Epub 2021 Jun 8.

Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People's Republic of China.

Background: The response rate of immunotherapy via immune checkpoint blockade in hepatocellular carcinoma (HCC) is limited due to multiple immune evasion mechanisms. OX40 is a T cell co-stimulating molecule which suppresses the cancer immune evasion by activating effector T cells (Teffs) and counteracting regulatory T cells (Tregs). TLR9 belongs to the toll-like receptor superfamily which promotes tumour antigen presentation by stimulating the maturation of dendritic cells. Read More

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Controlling the pandemic during the SARS-CoV-2 vaccination rollout.

Nat Commun 2021 06 16;12(1):3674. Epub 2021 Jun 16.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Read More

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Protection of coenzyme Q10 against contrast-induced acute kidney injury in male diabetic rats.

Diabetol Metab Syndr 2021 Jun 16;13(1):69. Epub 2021 Jun 16.

Laboratório Experimental de Modelos Animais (LEMA), Escola de Enfermagem da Universidade de São Paulo (EEUSP), Avenida Doutor Enéas de Carvalho Aguiar, 419, Cerqueira César, São Paulo, SP, 05403-000, Brazil.

Background: Diabetes mellitus (DM) is a major risk factor for contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI result in oxidative damage and inflammation that can be reduced when treated with the coenzyme Q-10 (CoQ10). The aim of this study was to investigate the therapeutic potential of CoQ10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats subjected to CI-AKI. Read More

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Olive leaf extract prevents obesity, cognitive decline, and depression and improves exercise capacity in mice.

Sci Rep 2021 Jun 14;11(1):12495. Epub 2021 Jun 14.

Nutrition Act. Co. Ltd., Tokyo, 104-0061, Japan.

Obesity is a risk factor for development of metabolic diseases and cognitive decline; therefore, obesity prevention is of paramount importance. Neuronal mitochondrial dysfunction induced by oxidative stress is an important mechanism underlying cognitive decline. Olive leaf extract contains large amounts of oleanolic acid, a transmembrane G protein-coupled receptor 5 (TGR5) agonist, and oleuropein, an antioxidant. Read More

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Upper-Extremity Phlegmasia Cerulea Dolens with Compartment Syndrome in Coronavirus Disease 2019 Sepsis.

J Hand Surg Am 2021 May 4. Epub 2021 May 4.

Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX.

A 54-year-old woman with leukemia presented with coronavirus disease 2019 and a right upper-extremity indwelling peripherally inserted central catheter line for chemotherapy administration. On hospital admission day 9, she developed acute right upper-extremity edema and pain. Ultrasound demonstrated complete superficial and deep venous thrombosis up to the proximal subclavian vein. Read More

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Pharmacological mechanisms underlying the efficacy of antibodies generated by a vaccine to treat oxycodone use disorder.

Neuropharmacology 2021 Jun 11:108653. Epub 2021 Jun 11.

University of Minnesota Medical School, Department of Pharmacology; Hennepin Healthcare Research Institute; University of Minnesota Medical School, Department of Medicine; University of Minnesota Center for Immunology.

Therapeutic vaccines offer a viable strategy to treat opioid use disorders (OUD) complementary to current pharmacotherapies. The candidate Oxy(Gly)-sKLH vaccine targeting oxycodone displayed pre-clinical proof of efficacy, selectivity and safety, and it is now undergoing clinical evaluation. To further support its implementation in the clinic, this study tested critical in vivo neuropsychopharmacological properties of the Oxy(Gly)-sKLH vaccine in rats. Read More

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Postprandial Hypotension in the Intensive Care Unit Due To Portal Hypertension and Coronavirus Disease 2019: A Case Report.

A A Pract 2021 Jun 14;15(6):e01485. Epub 2021 Jun 14.

Anesthesiology, University of Wisconsin Hospitals and Clinics, Madison, Wisconsin.

A 49-year-old man with cirrhosis and portal hypertension was admitted for acute respiratory distress syndrome secondary to coronavirus disease 2019 (COVID-19) pneumonia. His course was complicated by postprandial hypotension (PPH)-episodic hemodynamic collapse that occurred minutes after enteral administration of medications or fluids. Octreotide, which reduces splanchnic pooling and can treat PPH, successfully prevented ongoing events. Read More

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Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures.

Front Cell Neurosci 2021 28;15:688905. Epub 2021 May 28.

Department of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.

Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation. Read More

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Effects of zoledronic acid on osteonecrosis and acute lymphoblastic leukemia treatment efficacy in preclinical models.

Pediatr Blood Cancer 2021 Jun 14:e29183. Epub 2021 Jun 14.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Osteonecrosis is a devastating side effect of acute lymphoblastic leukemia (ALL) therapy. Associations between bone density loss and osteonecrosis have sparked interest in using bisphosphonates to reduce this complication.

Procedure: We assessed the impact of zoledronic acid (ZA) on the development of osteonecrosis in murine models when used either throughout therapy (continuous administration) or late in therapy after vascular lesions have developed but before osteonecrosis has occurred. Read More

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Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats.

J Chem Neuroanat 2021 Jun 10;116:101986. Epub 2021 Jun 10.

Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Science, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Read More

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