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https://www.readbyqxmd.com/read/29346549/transcriptome-and-functional-analysis-in-a-drosophila-model-of-ngly1-deficiency-provides-insight-into-therapeutic-approaches
#1
Katie G Owings, Joshua B Lowry, Yiling Bi, Matthew Might, Clement Y Chow
Autosomal recessive loss-of-function mutations in N-Glycanase 1 (NGLY1) cause NGLY1 deficiency, the only known human disease of deglycosylation. Patients present with developmental delay, movement disorder, seizures, liver dysfunction, and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD and other cellular processes and results in the constellation of problems associated with NGLY1 deficiency...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29344472/status-epilepticus-as-an-unusual-manifestation-of-heat-stroke
#2
Won Gu Lee, So-Young Huh, Jin-Hyung Lee, Bong Goo Yoo, Meyung Kug Kim
Heat stroke (HS) is a medical emergency and life threatening condition, characterized by body temperature over 40°C. This can lead to dysfunction of multiple organs such as the heart, liver, kidneys, lungs, blood coagulation system, and central nervous system. Neurological complications include change in consciousness, cerebellar dysfunction, convulsions, aphasia, muscular weakness, and parkinsonism. Cerebellar syndrome is the most common neurological finding in HS. We report a case of HS presenting with status epilepticus, without any other neurological manifestations...
December 2017: Journal of Epilepsy Research
https://www.readbyqxmd.com/read/29343773/mitochondrial-mutations-in-cholestatic-liver-disease-with-biliary-atresia
#3
Hong Koh, Gun-Seok Park, Sun-Mi Shin, Chang Eon Park, Seung Kim, Seok Joo Han, Huy Quang Pham, Jae-Ho Shin, Dong-Woo Lee
Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343286/diagnosis-and-management-of-transthyretin-familial-amyloid-polyneuropathy-in-japan-red-flag-symptom-clusters-and-treatment-algorithm
#4
REVIEW
Yoshiki Sekijima, Mitsuharu Ueda, Haruki Koike, Sonoko Misawa, Tomonori Ishii, Yukio Ando
Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare systemic disorder predominantly characterized by irreversible, progressive, and persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, which form amyloid fibrils that deposit in peripheral nerves and various organs, giving rise to peripheral and autonomic neuropathy and several non-disease specific symptoms...
January 17, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29341948/biochemical-changes-in-experimental-rat-model-of-abdominal-compartment-syndrome
#5
Raina G Ardasheva, Mariana D Argirova, Valentin I Turiiski, Athanas D Krustev
BACKGROUND: Increased intra-abdominal pressure (IAP) causes tissue ischemia, subsequent hypoxia, and impairment of normal tissue metabolism. Elevation of IAP above 20 mmHg leads to progression of abdominal compartment syndrome (ACS) that is associated with organ dysfunction or failure not previously manifested. AIM: To evaluate the eff ects of diff erent grades and time of exposure to IAP on biochemical parameters and oxidative stress in organs aff ected by ischemia using previously developed rat model...
December 20, 2017: Folia Medica
https://www.readbyqxmd.com/read/29341879/mechanisms-of-mitochondrial-toxicity-of-the-kinase-inhibitors-ponatinib-regorafenib-and-sorafenib-in-human-hepatic-hepg2-cells
#6
Franziska Paech, Cécile Mingard, David Grünig, Vanessa F Abegg, Jamal Bouitbir, Stephan Krähenbühl
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 hours, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 hours and in isolated mouse liver mitochondria exposed acutely...
January 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29341040/risk-factors-for-allograft-failure-in-liver-transplant-recipients
#7
Anna Huesing-Kabar, Christina Zu Dohna, Hauke Heinzow, Vito Rosario Cicinnati, Susanne Beckebaum, Martina Schmidt, Hans Ulrich Gerth, Michele Pohlen, Christian Wilms, Daniel Palmes, Hartmut Hans-Jürgen Schmidt, Iyad Kabar
BACKGROUND:  With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. MATERIAL AND METHODS:  A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study...
January 16, 2018: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29340015/apatinib-alone-or-combined-with-radiotherapy-in-metastatic-prostate-cancer-results-from-a-pilot-multicenter-study
#8
Feng Zhao, Wei Tian, Ming Zeng, Jianling Xia, Honglin Hu, Xinbao Hao, Liangfu Han, Hao Liu, Yangke He, Xueqiang Zhu, Liang Liang, Rui Ao, Min Wei, Lili Deng, Yuquan Wei
Background: To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339101/atherogenic-diet-induced-lipid-accumulation-induced-nf%C3%AE%C2%BAb-level-in-heart-liver-and-brain-of-wistar-rat-and-diosgenin-as-an-anti-inflammatory-agent
#9
Ambika Binesh, Sivasithamparam Niranjali Devaraj, Devaraj Halagowder
Atherogenic Diet (AD) was given to rats to understand the key role of inflammatory mediators in atherosclerotic lesion formation, as a serendipitous study, the diet induced inflammatory mediators in liver and brain, whereas pancreas, kidney and spleen were not affected. The efficacy of diosgenin in ameliorating atherosclerotic progression in heart and suppression of inflammatory mediators in liver and brain of Wistar rat fed on AD diet was investigated. Atherogenic diet triggered inflammatory mediators in heart, liver and brain by upregulating TNF-α, COX-2 and NFkBp65 which are the inflammatory hub, played a key role in pathophysiologic conditions...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29336468/increased-expression-of-sterol-regulatory-element-binding-protein%C3%A2-2-alleviates-autophagic-dysfunction-in-nafld
#10
Chunwei Cheng, Xiaoling Deng, Keshu Xu
Sterol regulatory element binding protein‑2 (SREBP‑2) is an important transcription factor in lipid homeostasis. A previous study showed that SREBP‑2 also activated autophagic genes during cell‑sterol depletion. Alterations in autophagy are reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, whether the regulation of SREBP‑2 restores dysfunctional autophagy in hepatocytes during NAFLD remains to be elucidated. In the present study, a steatosis model was established with palmitic acid (PA) treatment at the indicated times and concentrations...
January 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29335808/perfluorooctanoic-acid-impaired-glucose-homeostasis-through-affecting-adipose-akt-pathway
#11
Gang Du, Jinhong Sun, Yang Zhang
Perfluorooctanoic acid (PFOA) is commonly applied in manufactured products, and its potential health risk is concerned greatly. Increasing evidences have indicated PFOA-induced liver dysfunction. However, detailed molecular mechanism has not been completely identified. In this study, we aimed to investigate the mechanical association between PFOA exposure and AKT pathway in white adipose tissue. As results, PFOA-treated mice showed increased blood glucose and insulin levels, and induced insulin resistance. In addition, serum levels of leptin and adiponectin in PFOA-treated mice were elevated...
January 16, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29334960/arsenic-exposure-and-risk-of-nonalcoholic-fatty-liver-disease-nafld-among-u-s-adolescents-and-adults-an-association-modified-by-race-ethnicity-nhanes-2005-2014
#12
Jennifer K Frediani, Eric A Naioti, Miriam B Vos, Janet Figueroa, Carmen J Marsit, Jean A Welsh
BACKGROUND: While associated with obesity, the cause of the rapid rise in prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is highest among Hispanics, is not well understood. Animal experiments have demonstrated that arsenic exposure contributes to liver injury. Our objective was to examine the association between arsenic exposure and NAFLD in humans and to determine if race/ethnicity modifies the association. METHODS: Urinary inorganic arsenic concentrations among those ≥12 years in the National Health and Nutrition Examination Survey, 2005-2014 were used to assess the cross-sectional association with serum alanine aminotransferase (ALT) levels, a marker of liver dysfunction...
January 15, 2018: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/29334749/-unusual-history-of-wilson-disease-a-case-report-and-review-of-the-literature
#13
František Nehaj, Marianna Kubašková, Michal Mokáň, Juraj Sokol, Vladimír Nosáľ, Kamil Zeleňák, Marián Mokáň
Wilson disease (WD) belongs to autosomal recessive genetic metabolic disorders with gene mutation ATP7B located on 13th chromosome. The enzyme ATPase plays an important role in WD. It facilitates excretion of copper into bile. This gene is responsible for modification of apoceruloplasmin. In this disease, it leads to insufficient release of copper from organism and accumulation of copper in organs such as liver, brain which can cause dysfunction of a certain organ. According to specific symptoms, we can divide WD into psychiatric, neurologic or hepatic form...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29334530/antegrade-arterial-and-portal-flushing-versus-portal-flushing-only-for-right-lobe-live-donor-liver-transplantation-a-randomized-control-trial
#14
Viniyendra Pamecha, Rommel Sandhyav, Piyush Kumar Sinha, Kishore Gurumoorthy Subramanya Bharathy, Shridhar Sasturkar
INTRODUCTION: In live donor liver transplantation (LDLT) portal flush only of the graft is done on the bench. There is no data on antegrade arterial flush along with portal flush of the graft. METHODS: Consecutive patients undergoing elective right lobe LDLT were block-randomized to receive either portal flush only or both portal and antegrade arterial flush. The primary objectives were safety, rate of early allograft dysfunction (EAD), and impact on vascular and biliary complications RESULTS: After randomization there were 40 patients in each group...
January 12, 2018: Transplantation
https://www.readbyqxmd.com/read/29331339/cardiopulmonary-hemodynamics-and-c-reactive-protein-as-prognostic-indicators-in-compensated-and-decompensated-cirrhosis
#15
Laura Turco, Guadalupe Garcia-Tsao, Ilenia Magnani, Marcello Bianchini, Martina Costetti, Cristian Caporali, Stefano Colopi, Emilio Simonini, Nicola De Maria, Federico Banchelli, Rosario Rossi, Erica Villa, Filippo Schepis
BACKGROUND AND AIMS: The main stages of cirrhosis (compensated and decompensated) have been substaged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient, HVPG) features. Vasodilatation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage with inflammation being currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C reactive protein, CRP) among the different substages of cirrhosis and to investigate their interrelationship and prognostic relevance...
January 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#16
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29330965/intra-hepatic-bile-duct-primary-cilia-in-biliary-atresia
#17
Roberta Frassetto, Filippo Parolini, Salvatore Marceddu, Giulia Satta, Valeria Papacciuoli, Maria Antonia Pinna, Alessandra Mela, Giannina Secchi, Grazia Galleri, Roberto Manetti, Luisa Bercich, Vincenzo Villanacci, Antonio Dessanti, Roberto Antonucci, Francesco Tanda, Daniele Alberti, Kathleen B Schwarz, Maria Grazia Clemente
AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The primary aim was to investigate intra-hepatic bile duct cilia (IHBC) in BA at the diagnosis and correlation with clinical outcome. The secondary aim was to analyze IHBC in routine paraffin-embedded liver biopsies using conventional scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at the diagnosis from 22 BA infants (age range: 39 - 116 days) and from 8 children with non-BA chronic cholestasis (age range: 162 days -16,8 years) were evaluated for IHBC, both by immunofluorescence (IF) and by SEM...
January 13, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29330881/cocaine-and-hiv-1-tat-disrupt-cholesterol-homeostasis-in-astrocytes-implications-for-hiv-associated-neurocognitive-disorders-in-cocaine-user-patients
#18
Bianca Cotto, Kalimuthusamy Natarajaseenivasan, Kimberly Ferrero, Leroy Wesley, Matthew Sayre, Dianne Langford
Cholesterol synthesis and clearance by astrocytes are tightly regulated to maintain constant levels within the brain. In this context, liver X receptors (LXRs) are the master regulators of cholesterol homeostasis in the central nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR activation leading to the transcription of target genes involved in cholesterol trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, and several ATP-binding cassette transporter proteins...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29330372/non-estrogenic-xanthohumol-derivatives-mitigate-insulin-resistance-and-cognitive-impairment-in-high-fat-diet-induced-obese-mice
#19
Cristobal L Miranda, Lance A Johnson, Oriane de Montgolfier, Valerie D Elias, Lea S Ullrich, Joshua J Hay, Ines L Paraiso, Jaewoo Choi, Ralph L Reed, Johana S Revel, Chrissa Kioussi, Gerd Bobe, Urszula T Iwaniec, Russell T Turner, Benita S Katzenellenbogen, John A Katzenellenbogen, Paul R Blakemore, Adrian F Gombart, Claudia S Maier, Jacob Raber, Jan F Stevens
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#20
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
January 12, 2018: Journal of the American Society of Nephrology: JASN
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