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International Journal of Molecular... Feb 2023Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and... (Review)
Review
Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and enzymatic activity. Ubiquitin-specific proteases (USPs) constitute the largest deubiquitinating enzyme family. To date, accumulating evidence indicates that several USPs positively and negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 14, 15, 22, 36, and 48 modulate the progression of diabetic nephropathy, neuropathy, and/or retinopathy. USP4, 10, and 18 in hepatocytes ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic USP2, 11, 14, 19, and 20 exacerbate it. The roles of USP7 and 22 in hepatic disorders are controversial. USP9X, 14, 17, and 20 in vascular cells are postulated to be determinants of atherosclerosis. Moreover, mutations in the and loci in pituitary tumors cause Cushing syndrome. This review summarizes the current knowledge about the modulatory roles of USPs in energy metabolic disorders.
Topics: Humans; Ubiquitin-Specific Proteases; Ubiquitination; Hepatocytes; Non-alcoholic Fatty Liver Disease; Ubiquitin Thiolesterase; Ubiquitin-Specific Peptidase 7; Endopeptidases
PubMed: 36834633
DOI: 10.3390/ijms24043219 -
Revue Medicale de Liege May 2019Chronic alcohol consumption results in multiple peripheral and central nervous system dysfunctions. Some are due to the direct action of alcohol or its derivatives,... (Review)
Review
Chronic alcohol consumption results in multiple peripheral and central nervous system dysfunctions. Some are due to the direct action of alcohol or its derivatives, others are induced by the vitamin deficiencies associated with alcoholism, others are eventually related to the failure of other vital organs, such as the liver. In this short review, we describe alcohol-induced neuropathy, Gayet-Wernicke syndrome, Korsakoff syndrome, alcoholic dementia, Marchiafava-Bignami syndrome, hepatic encephalopathy, alcoholic epilepsy and manifestations of alcohol withdrawal.
Topics: Alcoholism; Dementia; Hepatic Encephalopathy; Humans; Wernicke Encephalopathy
PubMed: 31206272
DOI: No ID Found -
Journal of Clinical Medicine Nov 2022The purpose of this article is to improve recognition and treatment of Wernicke-Korsakoff syndrome. It is well known that Korsakoff syndrome is a chronic amnesia... (Review)
Review
The purpose of this article is to improve recognition and treatment of Wernicke-Korsakoff syndrome. It is well known that Korsakoff syndrome is a chronic amnesia resulting from unrecognized or undertreated Wernicke encephalopathy and is caused by thiamine (vitamin B1) deficiency. The clinical presentation of thiamine deficiency includes loss of appetite, dizziness, tachycardia, and urinary bladder retention. These symptoms can be attributed to anticholinergic autonomic dysfunction, as well as confusion or delirium, which is part of the classic triad of Wernicke encephalopathy. Severe concomitant infections including sepsis of unknown origin are common during the Wernicke phase. These infections can be prodromal signs of severe thiamine deficiency, as has been shown in select case descriptions which present infections and lactic acidosis. The clinical symptoms of Wernicke delirium commonly arise within a few days before or during hospitalization and may occur as part of a refeeding syndrome. Wernicke encephalopathy is mostly related to alcohol addiction, but can also occur in other conditions, such as bariatric surgery, hyperemesis gravidarum, and anorexia nervosa. Alcohol related Wernicke encephalopathy may be identified by the presence of a delirium in malnourished alcoholic patients who have trouble walking. The onset of non-alcohol-related Wernicke encephalopathy is often characterized by vomiting, weight loss, and symptoms such as visual complaints due to optic neuropathy in thiamine deficiency. Regarding thiamine therapy, patients with hypomagnesemia may fail to respond to thiamine. This may especially be the case in the context of alcohol withdrawal or in adverse side effects of proton pump inhibitors combined with diuretics. Clinician awareness of the clinical significance of Wernicke delirium, urinary bladder retention, comorbid infections, refeeding syndrome, and hypomagnesemia may contribute to the recognition and treatment of the Wernicke-Korsakoff syndrome.
PubMed: 36431232
DOI: 10.3390/jcm11226755 -
Cell Metabolism Mar 2021The nervous system instructs the body's metabolism, including that in the liver. However, the neural anatomy of the liver under either normal or metabolically stressed...
The nervous system instructs the body's metabolism, including that in the liver. However, the neural anatomy of the liver under either normal or metabolically stressed conditions remains to be unequivocally assessed. Here, we examined neural distributions in the mouse, nonhuman primate, and human livers with advanced 3D imaging. We observed that neural innervations within the liver are predominantly sympathetic, but not parasympathetic, inputs. Moreover, we discovered the profound and reversible loss of such sympathetic innervations during metabolic challenges. This hepatic sympathetic neuropathy was caused by TNFα derived from CD11b F4/80 immune cells under high-fat-diet (HFD) condition. We further demonstrated that the Sarm1 deletion mitigated the hepatic sympathetic neuropathy and improved metabolic parameters in HFD-challenged mice. Mechanistically, the sympathetic neurotransmitter norepinephrine attenuated the immune-cell inflammation that would otherwise trigger the insulin insensitivity of hepatocytes. These results together reveal the previously unrecognized neuropathic event in the liver with metabolic relevance.
Topics: Animals; Armadillo Domain Proteins; Cytoskeletal Proteins; Diet, High-Fat; Humans; Liver; Lymphocytes; Macaca mulatta; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Norepinephrine; Stress, Physiological; Tumor Necrosis Factor-alpha
PubMed: 33545051
DOI: 10.1016/j.cmet.2021.01.012 -
Journal of Neurology Dec 2019The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to... (Meta-Analysis)
Meta-Analysis
The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to identify the most appropriate management strategies. In this review, possible pathogenetic mechanisms are also discussed. A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. 87 articles were included in this review, 29 case-control studies, 52 prospective/retrospective cohort studies and 2 randomised control trials, 1 cross sectional study, and 3 population-based studies. The prevalence of peripheral neuropathy amongst chronic alcohol abusers is 46.3% (CI 35.7- 57.3%) when confirmed via nerve conduction studies. Alcohol-related peripheral neuropathy generally presents as a progressive, predominantly sensory axonal length-dependent neuropathy. The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. At present, it is unclear what the pathogenetic mechanisms for the development of neuropathy amongst those who chronically abuse alcohol are, and therefore, it is unknown whether it is attributed to the direct toxic effects of ethanol or another currently unidentified factor. There is presently sparse data to support a particular management strategy in alcohol-related peripheral neuropathy, but the limited data available appears to support the use of vitamin supplementation, particularly of B-vitamin regimens inclusive of thiamine.
Topics: Alcoholic Neuropathy; Humans; Peripheral Nervous System Diseases
PubMed: 30467601
DOI: 10.1007/s00415-018-9123-1 -
IBRO Neuroscience Reports Dec 2022Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to...
Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to sensory, autonomic, and motor dysfunctions. Despite many studies, the pathogenesis of these lesions is still not completely understood. We investigated few aspects on the development of alcohol-induced peripheral neuropathy, by assessing sensory, motor and autonomic functions, as well as stereological analysis of axonal fibers and myelin sheath of the sciatic nerve. Twelve male Wistar rats were divided into Control group and Alcohol group that was submitted to Two Bottle-Choice Paradigm of intermittent and voluntary alcohol solution intake (20%; v/v) during eight weeks. At the end of treatment, three different sensorium-motor tests were applied - Tactile Sensitivity, Thermal Sensitivity, and Functional Observational Battery (FOB). Quantitative morphometric analysis of sciatic nerve structures was performed by stereological method. Alcohol concentration in the blood was measured to analyze possible correlation between availability of alcohol in the blood and the magnitude of the peripheral nerve lesion. Our data showed a peripheral effect of chronic alcohol intake associated with hyperalgesia and a process of demyelination with a strong correlation with alcohol consumption. This process was associated with increased tactile sensitivity, with behavioral reflexes such as locomotor hyperactivity, changes in gait and balance, and autonomic reflexes such as piloerection.
PubMed: 36065406
DOI: 10.1016/j.ibneur.2022.08.004 -
World Journal of Hepatology May 2015Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the... (Review)
Review
Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels (a "marker" of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.
PubMed: 26019741
DOI: 10.4254/wjh.v7.i9.1258 -
Pharmacological Research Oct 2023There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a... (Review)
Review
There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.
PubMed: 37703962
DOI: 10.1016/j.phrs.2023.106918 -
Frontiers in Endocrinology 2023Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator... (Review)
Review
Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.
Topics: Animals; Humans; C-Peptide; Quality of Life; Diabetes Complications; Diabetes Mellitus
PubMed: 37745697
DOI: 10.3389/fendo.2023.1256093