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https://www.readbyqxmd.com/read/27923157/adjuvant-neuronal-nitric-oxide-synthase-inhibition-for-combined-treatment-of-epilepsy-and-comorbid-depression
#1
Tanveer Singh, Rajesh Kumar Goel
BACKGROUND: Elevated nitric oxide (NO) levels in the brain have been apparently associated with depression in kindled animals. Owing to the major role of neuronal nitric oxide synthase (nNOS) in brain and ineffectiveness of antiepileptic drugs (AEDs) in restoring nitrosative stress, the present study was envisaged to evaluate the adjuvant nNOS inhibitor, 7-nitroindazole (7-NI) with valproic acid for combined treatment of epilepsy and associated depression. METHODS: Pentylenetetrazole kindled animals associated with depression were treated with vehicle, valproate (300mg/kg/day ip), valproate with 7-NI (10mg/kg; 20mg/kg; 40mg/kg)/day ip and 7-NI (40mg/kg/day ip) for 15days...
October 4, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27920727/genetic-targeting-of-arginase-ii-in-mouse-prevents-renal-oxidative-stress-and-inflammation-in-diet-induced-obesity
#2
Ji Huang, Angana Rajapakse, Yuyan Xiong, Jean-Pierre Montani, François Verrey, Xiu-Fen Ming, Zhihong Yang
Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27920723/sex-dependent-anti-stress-effect-of-an-%C3%AE-5-subunit-containing-gabaa-receptor-positive-allosteric-modulator
#3
Sean C Piantadosi, Beverly J French, Michael M Poe, Tamara Timić, Bojan D Marković, Mohan Pabba, Marianne L Seney, Hyunjung Oh, Beverley A Orser, Miroslav M Savić, James M Cook, Etienne Sibille
Rationale: Current first-line treatments for stress-related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "α5-PAM"), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27917785/dipyrone-ameliorates-behavioural-changes-induced-by-unpredictable-chronic-mild-stress-gender-differences
#4
Olcay E Kiroğlu, Kübra E Demirkol, Fatih Berktaş, Arash A Yegani, Ayşegül Kirpik, Erkan Maytalman, Mahmut Ünverdi, Fazilet Aksu
PURPOSE: Antidepressant effects of analgesics have been investigate in both clinical and experimental studies. The purpose of this study was to investigate if the analgesic-antipyretic drug, dipyrone, also had antidepressant-like effects. METHODS: Depression-like effects were investigated in an unpredictable chronic mild stress (UCMS) model in both male and female mice. Cage changes, light-dark cycle reversal, cage tilting, wet floor, empty cage, foreign material on the floor and predator sounds were used to induce light stress at different times for six weeks...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27916702/chronic-kidney-disease-accelerates-cognitive-impairment-in-a-mouse-model-of-alzheimer-s-disease-through-angiotensin-ii
#5
Takashi Nakagawa, Yu Hasegawa, Ken Uekawa, Shokei Kim-Mitsuyama
Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding adenine-containing diet and the effect on cognitive function was compared between both strains...
December 1, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27916681/surfactant-protein-a-deficiency-exacerbates-renal-interstitial-fibrosis-following-obstructive-injury-in-mice
#6
Shaojiang Tian, Chenxiao Li, Ran Ran, Shi-You Chen
Renal interstitial fibrosis is an inevitable consequence of virtually every type of chronic kidney disease. The underlying mechanisms, however, are not completely understood. In the present study, we identified surfactant protein A (SP-A) as a novel protein factor involved in the renal fibrosis induced by unilateral ureter obstruction (UUO). UUO induced SP-A expression in mouse kidney epithelium, likely due to the increased acidic stress and inflammation. Interestingly, SP-A deficiency aggravated UUO-prompted kidney structural damage, macrophage accumulation, and tubulointerstitial fibrosis...
December 1, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913104/d-ala2-gip-glu-pal-is-neuroprotective-in-a-chronic-parkinson-s-disease-mouse-model-and-increases-bndf-expression-while-reducing-neuroinflammation-and-lipid-peroxidation
#7
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Parkinson's disease (PD). Therefore, treatment to improve insulin resistance in T2DM may be useful for PD patients. Glucose dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family that can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. We had shown previously that D-Ala2-GIP-glu-PAL, a novel long-acting GIP analogue, can play a neuroprotective role in the PD mouse model induced by acute MPTP injection...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27910070/mig-6-mouse-model-of-endometrial-cancer
#8
Tae Hoon Kim, Jung-Yoon Yoo, Jae-Wook Jeong
Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferation. P4 antagonizes the growth-promoting properties of E2 in the uterus. P4 prevents the development of endometrial cancer associated with unopposed E2 by blocking E2 actions. Mitogen inducible gene 6 (Mig-6, Errfi1, RALT, or gene 33) is an immediate early response gene that can be induced by various mitogens and common chronic stress stimuli...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27909224/sarcomeric-protein-modification-during-adrenergic-stress-enhances-cross-bridge-kinetics-and-cardiac-output
#9
Kenneth S Gresham, Ranganath Mamidi, Jiayang Li, Hyerin Kwak, Julian E Stelzer
Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on post-translational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine; IPE) for 14 days using implantable osmotic pumps...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27908553/olive-polyphenol-effects-in-a-mouse-model-of-chronic-ethanol-addiction
#10
Valentina Carito, Mauro Ceccanti, Vincenzo Cestari, Fausta Natella, Cristiano Bello, Roberto Coccurello, Rosanna Mancinelli, Marco Fiore
OBJECTIVES: Alcohol addiction elicits oxidative imbalance and it is well known that polyphenols possess antioxidant properties. We investigated whether or not polyphenols could confer a protective potential against alcohol-induced oxidative stress. METHODS: We administered (per os) for two months 20 mg/kg of olive polyphenols containing mostly hydroxytyrosol in alcoholic adult male mice. Hydroxytyrosol metabolites as hydroxytyrosol sulfate 1 and hydroxytyrosol sulfate 2 were found in the serum of mice administered with polyphenols with the highest amount in animals treated with both polyphenols and alcohol...
January 2017: Nutrition
https://www.readbyqxmd.com/read/27908234/sustained-early-disruption-of-mitochondrial-function-contributes-to-arsenic-induced-prostate-tumorigenesis
#11
B Singh, M Kulawiec, K M Owens, A Singh, K K Singh
Arsenic is a well-known human carcinogen that affects millions of people worldwide, but the underlying mechanisms of carcinogenesis are unclear. Several epidemiological studies have suggested increased prostate cancer incidence and mortality due to exposure to arsenic. Due to lack of an animal model of arsenic-induced carcinogenesis, we used a prostate epithelial cell culture model to identify a role for mitochondria in arsenic-induced prostate cancer. Mitochondrial morphology and membrane potential was impacted within a few hours of arsenic exposure of non-neoplastic prostate epithelial cells...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907040/the-role-of-reactive-oxygen-species-in-%C3%AE-adrenergic-signaling-in-cardiomyocytes-from-mice-with-the-metabolic-syndrome
#12
Monica Llano-Diez, Jon Sinclair, Takashi Yamada, Mei Zong, Jeremy Fauconnier, Shi-Jin Zhang, Abram Katz, Kent Jardemark, Håkan Westerblad, Daniel C Andersson, Johanna T Lanner
The metabolic syndrome is associated with prolonged stress and hyperactivity of the sympathetic nervous system and afflicted subjects are prone to develop cardiovascular disease. Under normal conditions, the cardiomyocyte response to acute β-adrenergic stimulation partly depends on increased production of reactive oxygen species (ROS). Here we investigated the interplay between beta-adrenergic signaling, ROS and cardiac contractility using freshly isolated cardiomyocytes and whole hearts from two mouse models with the metabolic syndrome (high-fat diet and ob/ob mice)...
2016: PloS One
https://www.readbyqxmd.com/read/27907022/nicotine-induces-podocyte-apoptosis-through-increasing-oxidative-stress
#13
Xiqian Lan, Rivka Lederman, Judith M Eng, Seyedeh Shadafarin Marashi Shoshtari, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
BACKGROUND: Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury. METHODS: To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining...
2016: PloS One
https://www.readbyqxmd.com/read/27902980/gene-expression-profiling-and-functional-characterization-of-macrophages-in-response-to-circulatory-microparticles-produced-during-trypanosoma-cruzi-infection-and-chagas-disease
#14
Imran H Chowdhury, Sue-Jie Koo, Shivali Gupta, Lisa Yi Liang, Bojlul Bahar, Laura Silla, Julio Nuñez-Burgos, Natalia Barrientos, Maria Paola Zago, Nisha Jain Garg
BACKGROUND: Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHODS: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs...
December 1, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27899891/cardiac-stat3-deficiency-impairs-contractility-and-metabolic-homeostasis-in-hypertension
#15
Raffaele Altara, Romain Harmancey, Sean P Didion, George W Booz, Fouad A Zouein
Signal transducer and activator of transcription 3 (STAT3) protects the heart from acute ischemic stress. However, the importance of STAT3 to the heart in chronic stress, such as hypertension, is not known. To study this, we used cardiomyocyte-targeted STAT3 knockout (KO) mice and Angiotensin II (ANG II) infusion by osmotic minipumps. After 4 weeks, ANG II induced similar cardiac hypertrophy in wild type (WT) and cardiac Cre-expressing control (CTRL) mice with no impairment of cardiac function. In contrast, STAT3 KO mice exhibited reduced contractile function but similar hypertrophy to CTRL mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27897991/the-double-role-of-p53-in-cancer-and-autoimmunity-and-its-potential-as-therapeutic-target
#16
REVIEW
Alessandra Fierabracci, Marsha Pellegrino
p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27895319/activation-of-chronic-toxoplasmosis-by-transportation-stress-in-a-mouse-model
#17
Bang Shen, Yuan Yuan, Jianxi Cheng, Ming Pan, Ningbo Xia, Weichao Zhang, Yifan Wang, Yanqin Zhou, Junlong Zhao
Toxoplasma gondii is an obligate intracellular parasite infecting 25% of the world population and enormous number of animals. It can exist in two forms in intermediate hosts: the fast replicating tachyzoites responsible for acute infection and the slowly replicating bradyzoites responsible for life-long chronic infection. The interconversion between tachyzoites and bradyzoites plays critical roles in the transmission and pathogenesis of T. gondii. However, the molecular mechanisms that govern the interconversion are largely unknown...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890560/the-hippocampal-transcriptomic-signature-of-stress-resilience-in-mice-with-microglial-fractalkine-receptor-cx3cr1-deficiency
#18
Neta Rimmerman, Nofar Schottlender, Ronen Reshef, Nadav Dan-Goor, Raz Yirmiya
Clinical studies suggest that key genetic factors involved in stress resilience are related to the innate immune system. In the brain, this system includes microglia cells, which play a major role in stress responsiveness. Consistently, mice with deletion of the CX3CR1 gene (CX3CR1(-/-) mice), which in the brain is expressed exclusively by microglia, exhibit resilience to chronic stress. Here, we compared the emotional, cognitive, neurogenic and microglial responses to chronic unpredictable stress (CUS) between CX3CR1(-/-) and wild type (WT) mice...
November 23, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27882191/protective-effects-of-hydrogen-sulfide-in-the-ageing-kidney
#19
Cui-Lan Hou, Ming-Jie Wang, Chen Sun, Yong Huang, Sheng Jin, Xue-Pan Mu, Ying Chen, Yi-Chun Zhu
Aims. The study aimed to examine whether hydrogen sulfide (H2S) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. Results. H2S levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known H2S-producing enzymes in kidney, cystathionine γ-lyase (CSE) and cystathionine-β-synthase (CBS), decreased significantly during ageing. Chronic H2S donor (NaHS, 50 μmol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27880725/mouse-sirt3-promotes-autophagy-in-angii-induced-myocardial-hypertrophy-through-the-deacetylation-of-foxo1
#20
Jingyuan Li, Tongshuai Chen, Ming Xiao, Na Li, Shujian Wang, Hongyan Su, Xiaobin Guo, Hui Liu, Fangying Yan, Yi Yang, Yun Zhang, Peili Bu
Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy...
November 17, 2016: Oncotarget
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