المؤلفون: Narendra S. Choudhary, Neeraj Saraf, Swapnil Dhampalwar, Arvinder S. Soin

المصدر: Journal of Clinical and Experimental Hepatology

مصطلحات موضوعية: NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, ACLF, acute-on chronic liver failure, Cirrhosis, Coronavirus disease 2019 (COVID-19), liver diseases, ALT, alanine transaminase, NASH, non-alcoholic steatohepatitis, medicine.medical_treatment, LFT, liver function tests, Review Article, AST, aspartate aminotransferase, Liver transplantation, LT, liver transplantation, Chronic liver disease, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, Gastroenterology, MELD, model for end-stage liver disease, 03 medical and health sciences, 0302 clinical medicine, HCWs, health care workers, Internal medicine, medicine, Risk of mortality, ALI, acute liver injury, In patient, COVID-19, Coronavirus disease 2019, immunosuppression, Hepatology, SARS-CoV-2, business.industry, NASH, ACE, angiotensin converting enzyme related carboxypeptidase receptors, Immunosuppression, medicine.disease, Decompensated cirrhosis, mortality, HR, hazard ratio, 030220 oncology & carcinogenesis, CLD, chronic liver disease, 030211 gastroenterology & hepatology, business, OR, Odds ratio

الوصف: Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to non-cirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a3c248e064d1e6f7878934db19f6d0fTest
https://doi.org/10.1016/j.jceh.2021.05.003Test

المؤلفون: Bilal Hameed, Neil Mehta, Amit G. Singal, R. Katie Kelley, Neehar D. Parikh

المصدر: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, vol 19, iss 8
Clinical Gastroenterology and Hepatology

مصطلحات موضوعية: PD-L1, programmed death ligand 1, medicine.medical_treatment, Liver transplantation, Systemic therapy, 0302 clinical medicine, Model for End-Stage Liver Disease, Pandemic, alpha-fetoprotein (AFP), HCC, CMS, Centers for Medicare and Medicaid services, Cancer, COVID-19, Coronavirus disease 2019, AFP, alpha-fetoprotein, Liver Disease, Liver Neoplasms, BCLC, Barcelona Clinic Liver Cancer, Gastroenterology, RETREAT, Risk estimation of tumor recurrence after liver transplantation, LRT, local regional therapy, VEGF, vascular endothelial growth factor, Local, HCV, hepatitis C virus, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Screening, 030211 gastroenterology & hepatology, alpha-Fetoproteins, Patient Safety, Alpha-Fetoprotein, Liver Cancer, medicine.medical_specialty, Carcinoma, Hepatocellular, CTP, Child-Turcotte-Pugh, NASH, non-alcoholic steatohepatitis, AFP, Clinical Sciences, Context (language use), LT, liver transplantation, Lower risk, Article, 03 medical and health sciences, Rare Diseases, SBRT, stereotactic body radiotherapy, Clinical Research, GALAD, gender, age, AFP-L3, AFP, and DCP, medicine, AFP-L3, lectin-reactive alpha-fetoprotein, Humans, DCP, des-gamma carboxyprothrombin, Intensive care medicine, Adverse effect, Pandemics, RCT, randomized control trial, UNOS, United Network for Organ Sharing, Gastroenterology & Hepatology, Hepatology, SARS-CoV-2, business.industry, screening, MELD, Model for End Stage Liver Disease, Prevention, Carcinoma, COVID-19, Evaluation of treatments and therapeutic interventions, Hepatocellular, medicine.disease, TACE, trans-arterial chemoembolization, Coronavirus, HBV, hepatitis B virus, Neoplasm Recurrence, Good Health and Well Being, Neoplasm Recurrence, Local, HCC, hepatocellular carcinoma, Digestive Diseases, business

الوصف: The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors’ recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07686baa7bc3f15f14e5a0d806140ee4Test
https://doi.org/10.1016/j.cgh.2020.06.072Test

المؤلفون: Jie Li, Xiaoyun Zhu, Jie Zou, Hao Zhang, Dejuan Xiang, Ling-Yi Kong, Zhigui Su, Yanqiu Zhang

المصدر: Acta Pharmaceutica Sinica B, Vol 11, Iss 6, Pp 1578-1591 (2021)
Acta Pharmaceutica Sinica. B

مصطلحات موضوعية: Hepatocellular carcinoma, NASH, non-alcoholic steatohepatitis, Proliferation, Fructose 1,6-bisphosphatase, RM1-950, Carbohydrate metabolism, LIX1L, Limb and CNS expressed 1 like, Metastasis, 03 medical and health sciences, 0302 clinical medicine, FBP1, CCl4, carbon tetrachloride, miRNA, microRNA, medicine, shRNA, short-hairpin RNA, General Pharmacology, Toxicology and Pharmaceutics, 030304 developmental biology, Glucose metabolism, 0303 health sciences, Gene knockdown, ECAR, extracellular acidification rate, biology, business.industry, Gluconeogenesis, Cell migration, medicine.disease, Seq, sequencing, LIX1L, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Original Article, miR-21-3p, Therapeutics. Pharmacology, HCC, hepatocellular carcinoma, Liver cancer, business, EMT, epithelial–mesenchymal transition, FBP1, fructose-1,6-bisphosphatase 1, DEN, diethylnitrosamine

الوصف: Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice. Functional studies indicated that LIX1L overexpression elevated proliferation, migratory, invasive capacities of HCC cells in vitro, and promoted liver cancer growth and metastasis in vivo. LIX1L knockdown up-regulated fructose-1,6-bisphosphatase (FBP1) expression to reduce glucose consumption as well as lactate production. Mechanistically, LIX1L increased miR-21-3p expression, which targeted and suppressed FBP1, thereby promoting HCC growth and metastasis. MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration, invasion, and glucose metabolism. Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model. Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression, with implications for prognosis and treatment.
Graphical abstract Limb and CNS expressed 1 like (LIX1L) promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase. LIX1L and miR-21-3p may be important cellular targets for designing new therapies against liver cancer.Image 1

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c970bf879a240521753514a3be8c82cTest
https://doi.org/10.1016/j.apsb.2021.02.005Test

المؤلفون: Yoshio Sakai, Taro Yamashita, Yasuhito Imai, Oto Inoue, Kazuhide Higuchi, Tuyen Thuy Bich Ho, Soichiro Usui, Shuichi Kaneko, Yusuke Tsuchimoto, Akira Asai, Kuniaki Arai, Tatsuya Yamashita, Takashi Wada, Kenichi Yoshimura, Masao Honda, Shinya Fukunishi, Shinichiro Takashima, Kenichi Harada, Eishiro Mizukoshi, Toshinori Murayama, Masayuki Takamura, Alessandro Nasti, Akihiro Seki, Kazunori Kawaguchi

المصدر: Regenerative Therapy
Regenerative Therapy, Vol 18, Iss, Pp 97-101 (2021)

مصطلحات موضوعية: 0301 basic medicine, Medicine (General), medicine.medical_specialty, Cirrhosis, MSCs, mesenchymal stem cells, Adipose tissue dissociation device, NASH, non-alcoholic steatohepatitis, Biomedical Engineering, Adipose tissue, Gastroenterology, Biomaterials, Cell therapy, 03 medical and health sciences, R5-920, 0302 clinical medicine, Internal medicine, Fatty liver diseases, medicine, Adipose tissue-derived regenerative (stem) cells, Non-alcoholic steatohepatitis, QH573-671, business.industry, Fatty liver, Conductible, ADRCs, adipose tissue derived regenerative (stem) cells, medicine.disease, Clinical trial, 030104 developmental biology, PMDA, Japan Pharmaceuticals and Medical Devices Agency, Liver cirrhosis, Original Article, NAFLD, nonalcoholic fatty liver disease, Steatohepatitis, Stem cell, Cytology, business, 030217 neurology & neurosurgery, Developmental Biology

الوصف: Introduction Liver cirrhosis is the ultimate condition of chronic liver diseases. Non-alcoholic steatohepatitis and fatty liver diseases are emerging in association with metabolic syndrome largely due to excess nutrition. Stromal cells of adipose tissue are enriched mesenchymal stem cells which are pluripotent and immunomodulatory, which are expected to be applied for repairing/regenerative therapy of the impaired organs. Methods We conducted the multi-institutional clinical trial (Japanese UMIN Clinical Trial Registry: UMIN000022601) of cell therapy using freshly isolated autologous adipose tissue-derived regenerative (stem) cells (ADRCs), which are obtained by the investigational trial device, adipose tissue dissociation device, for liver cirrhosis patients due to non-alcoholic steatohepatitis or fatty liver disease, to exploratory assess efficacy as well as safety of this trial. We completed treatment and 24 weeks follow-up for 7 patients. Results We observed that 6 out of 7 patients' serum albumin concentration was improved. As for prothrombin activity, 5 out of 7 patients showed improvement. No trial-related adverse events, which were serious or non-serious, was observed. Besides, no malfunction of the investigational trial device was encountered. Conclusion Thus, treatment with autologous ADRCs obtained with the investigational trial device in steatohepatitis-related cirrhosis was confirmed to be safely conductible and potentially promising for the retaining or improving the impaired hepatic reserve.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::498cb8601adedc4119b89a161cd23e11Test
http://europepmc.org/articles/PMC8165289Test

المؤلفون: Raluca Pais, Rachel Ostroff, Stephen Harrison, Lars Friis Mikkelsen, Elisabeth Erhardtsen, Sudha Shankar, Kimmo Porthan, Jérôme Boursier, Antonia Sinisi, Michael Kalutkiewicz, Sven Francque, Miljen Martic, Vanessa Pellegrinelli, Phil N. Newsome, Guido Hanauer, Hannele Yki-Järvinen, Rebecca Darlay, Joel Myers, Carla Yunis, Salvatore Petta, Mette Skalshøi Kjær, Pablo Ortiz, Ann K. Daly, James H. Clark, Dina Tiniakos, Yasaman Vali, Hadi Zafarmand, Matej Orešič, Maurizio Parola, Estelle Sandt, Lori L. Jennings, Matt Kelly, Tuulia Hyötyläinen, Detlef Schuppan, Céline Fournier, Chiara Rosso, Diane E. Shevell, Maria Manuela Tonini, Paul Hockings, Aidan McGlinchey, Salma Akhtar, Mette Juul Fisker, Morten A. Karsdal, Diane Whalley, Melissa R. Miller, Aldo Trylesinski, Mattias Ekstedt, Stefan Neubauer, Jeremy M. Palmer, Partho Sen, Michael Pavlides, Per Qvist, Isabel Fernández, Luca Miele, Fabio Marra, Stergios Kechagias, Richard Torstenson, Katherine Johnson, Jean-François Dufour, Elisabetta Bugianesi, M. Julia Brosnan, George V. Papatheodoridis, Kay M. Pepin, Daniel Guldager Kring Rasmussen, Henrik Landgren, Rachel Queen, Simon Cockell, Michael Allison, Patrick M.M. Bossuyt, Rocío Gallego-Durán, Christian Rosenquist, Leigh Alexander, Elizabeth Shumbayawonda, Michele Vacca, Antonio Vidal-Puig, David Wenn, Rémy Hanf, Oscar Millet, Michalina Zatorska, R. Myers, José M. Mato, Jenny Lee, Theresa Tuthill, James Twiss, Ramy Younes, Peter Leary, Lynda Doward, Kristy Wonders, Guruprasad P. Aithal, Sarah Charlton, Vlad Ratziu, Cecília M. P. Rodrigues, Christian Trautwein, Helena Cortez-Pinto, Gideon Ho, Matt J. Barter, Judith Ertle, Jörn M. Schattenberg, Maria-Magdalena Balp, Yang-Lin Liu, Clifford A. Brass, Olivier Govaere, Amalia Gastaldelli, Sergio Rodriguez Cuenca, Pierre Chaumat, Fiona Oakley, Luca Valenti, Simon J. Cockell, Saskia W.C. van Mil, Ferenc E. Mózes, Andreas Geier, Timothy Hardy, Pierre Bedossa, Andrea Dennis, Richard L. Ehman, Charlotte Erpicum, Karine Clément, Jeremy F. L. Cobbold, Christopher P. Day, Rajarshi Banerjee, Manuel Romero-Gómez, Quentin M. Anstee, Adriaan G. Holleboom, Heather J. Cordell, Kevin L. Duffin, Diana Julie Leeming

المساهمون: Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Graduate School, Investigators, LITMUS Consortium, Johnson K., Leary P.J., Govaere O., Barter M.J., Charlton S.H., Cockell S.J., Tiniakos D., Zatorska M., Bedossa P., Brosnan M.J., Cobbold J.F., Ekstedt M., Aithal G.P., Clement K., Schattenberg J.M., Boursier J., Ratziu V., Bugianesi E., Anstee Q.M., Daly A.K., Clark J., Cordell H.J., Darlay R., Day C.P., Hardy T., Liu Y.-L., Oakley F., Palmer J., Queen R., Wonders K., Bossuyt P.M., Holleboom A.G., Zafarmand H., Vali Y., Lee J., Pais R., Schuppan D., Allison M., Cuenca S.R., Pellegrinelli V., Vacca M., Vidal-Puig A., Hyotylainen T., McGlinchey A., Oresic M., Sen P., Mato J., Millet O., Dufour J.-F., Harrison S., Neubauer S., Pavlides M., Mozes F., Akhtar S., Banerjee R., Kelly M., Shumbayawonda E., Dennis A., Erpicum C., Romero-Gomez M., Gallego-Duran R., Fernandez I., Karsdal M., Leeming D., Fisker M.J., Erhardtsen E., Rasmussen D., Qvist P., Sinisi A., Sandt E., Tonini M.M., Parola M., Rosso C., Marra F., Gastaldelli A., Francque S., Kechagias S., Yki-Jarvinen H., Porthan K., van Mil S., Papatheodoridis G., Cortez-Pinto H., Valenti L., Petta S., Miele L., Geier A., Trautwein C., Hockings P., Newsome P., Wenn D., Pereira Rodrigues C.M., Hanf R., Chaumat P., Rosenquist C., Trylesinski A., Ortiz P., Duffin K., Yunis C., Miller M., Tuthill T., Ertle J., Younes R., Alexander L., Ostroff R., Kjaer M.S., Mikkelsen L.F., Brass C., Jennings L., Balp M.-M., Martic M., Hanauer G., Shankar S., Torstenson R., Fournier C., Ehman R., Kalutkiewicz M., Pepin K., Myers J., Shevell D., Ho G., Landgren H., Myers R., Doward L., Whalley D., Twiss J., Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Kjær, Mette Skalshøi, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Fournier, Céline, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, Twiss, James, Clark, James, Cordell, Heather J., Darlay, Rebecca, Day, Christopher P., Hardy, Tim, Liu, Yang-Lin, Oakley, Fiona, Palmer, Jeremy, Queen, Rachel, Wonders, Kristy, Bossuyt, Patrick M., Holleboom, Adriaan G., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Clement, Karine, Pais, Raluca, Schuppan, Detlef, Allison, Michael, Cuenca, Sergio Rodriguez, Pellegrinelli, Vanessa, Vacca, Michele, Vidal-Puig, Antonio, Hyötyläinen, Tuulia, McGlinchey, Aidan, Orešič, Matej, Sen, Partho, Mato, Jose, Millet, Óscar, Dufour, Jean-Francois, Harrison, Stephen, Neubauer, Stefan, Pavlides, Michael, Mozes, Ferenc, Akhtar, Salma, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Erpicum, Charlotte, Romero-Gomez, Manuel, Gallego-Durán, Rocío, Fernández, Isabel, Karsdal, Morten, Leeming, Diana, Fisker, Mette Juul, Erhardtsen, Elisabeth, Rasmussen, Daniel, Qvist, Per, Sinisi, Antonia, Sandt, Estelle, Tonini, Maria Manuela, Parola, Maurizio, Rosso, Chiara, Marra, Fabio, Gastaldelli, Amalia, Francque, Sven, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Valenti, Luca, Petta, Salvatore, Miele, Luca, Geier, Andreas, Trautwein, Christian, Hockings, Paul, Newsome, Phil, Wenn, David, Pereira Rodrigues, Cecília Maria, Hanf, Rémy, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, Yunis, Carla

المصدر: JHEP Reports, 4(2):100409. Elsevier
JHEP Reports
JHEP Reports, Vol 4, Iss 2, Pp 100409-(2022)
JHEP reports 4(2), 100409 (2022). doi:10.1016/j.jhepr.2021.100409

مصطلحات موضوعية: SCORING SYSTEM, CPM, counts per million, AUROC, area under the receiver operating characteristic, RC799-869, AST, aspartate aminotransferase, MicroRNA, Non-alcoholic fatty liver disease, Biomarker, Sequencing, TGF-β, transforming growth factor-beta, Gastroenterology, STEATOHEPATITIS, Liver disease, 0302 clinical medicine, Fibrosis, miRNA, microRNA, logFC, log2 fold change, FIBROSIS, Immunology and Allergy, 0303 health sciences, education.field_of_study, NAS, NAFLD activity score, medicine.diagnostic_test, Fatty liver, GTEx, Genotype-Tissue Expression, Diseases of the digestive system. Gastroenterology, 3. Good health, Real-time polymerase chain reaction, Biomarker, MicroRNA, Non-alcoholic fatty liver disease, Sequencing, Liver biopsy, ACID, Biomarker (medicine), 030211 gastroenterology & hepatology, Life Sciences & Biomedicine, Research Article, EXPRESSION, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, Population, Gastroenterology and Hepatology, SAF, steatosis–activity–fibrosis, VALIDATION, ER, endoplasmic reticulum, 03 medical and health sciences, cDNA, complementary DNA, Internal medicine, ALT, alanine aminotransferase, Gastroenterologi, Internal Medicine, medicine, NAFL, non-alcoholic fatty liver, ALGORITHM, FIB-4, fibrosis-4, education, 030304 developmental biology, PCA, principal component analysis, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, FC, fold change, medicine.disease, digestive system diseases, FLIP, fatty liver inhibition of progression, Ct, cycle threshold, Steatosis, qPCR, quantitative PCR, business

الوصف: Background & Aims Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
Graphical abstract
Highlights • Serum miRNA was sequenced in 183 NAFLD cases of varying severity and 10 population controls. • Plasma levels of miR-193a-5p were significantly increased in patients with advanced fibrosis, high NAS scores, or high SAF scores. • Other miRNAs including miR378d and miR378e were also significantly increased in certain comparisons. • The findings for miR-193a-5p were replicated in a cohort of 372 additional NAFLD cases.

وصف الملف: application/pdf; Electronic-eCollection

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c39a3a5921e0d464a7b2b93c40ef52cTest
https://pure.amc.nl/en/publications/increased-serum-mir193a5p-during-nonalcoholic-fatty-liver-disease-progressionTest(bd6dd66c-d686-4b4d-be46-956a848f1f3b).html

المؤلفون: Masaru Ishii, Junichi Kikuta, Atsunori Tsuchiya, Masaaki Takamura, Kenji Nakajima, Hara Yukio, Masahiro Ogawa, Suguru Takeuchi, Shunsuke Nojiri, Yuichi Kojima, Junji Yamashita, Shuji Terai, Takayuki Watanabe

المصدر: Regenerative Therapy, Vol 11, Iss, Pp 269-281 (2019)
Regenerative Therapy

مصطلحات موضوعية: 0301 basic medicine, Cirrhosis, ALP, Alkaline phosphatase, Adipose tissue, PGE2, Prostaglandin E2, Pharmacology, medicine.disease_cause, Prostaglandin E synthase, SOD, Superoxide dismutase, Cell therapy, hypoMSCs, MSCs cultured under hypoxic oxygen (5% O2) conditions, 0302 clinical medicine, norMSCs, MSCs cultured under normal oxygen (21% O2) conditions, Fibrosis, CAGE, Cap analysis of gene expression, Prostaglandin E2, LPS, Lipopolysaccharide, lcsh:R5-920, biology, HHSteC, Human Hepatic Stellate Cells, Chemistry, lcsh:Cytology, 8-OHdG, DNA 8-hydroxy-2’-deoxyguanosine, ALB, Albumin, id-BMM, Induced Bone Marrow Derived Macrophage, Original Article, PGE2, lcsh:Medicine (General), medicine.drug, T-Bil, Total bilirubin, Biomedical Engineering, Biomaterials, 03 medical and health sciences, ECM, Extracellular matrix, Hypoxic condition, medicine, lcsh:QH573-671, MDA, Malondialdehyde, LC, Liver cirrhosis, NASH, Non-alcoholic steatohepatitis, miR210, Mesenchymal stem cell, ALT, Alanine aminotransferase, MSCs, Mesenchymal stem cells, medicine.disease, 030104 developmental biology, Liver cirrhosis, biology.protein, Mesenchymal stem cells, PCR, Polymerase chain reaction, CCl4, Carbon tetrachloride, 030217 neurology & neurosurgery, Oxidative stress, Developmental Biology

الوصف: Background Mesenchymal stem cells (MSCs) can be easily expanded. They can be acquired from medical waste such as adipose and umbilical cord tissues, are influenced by culturing conditions, and exert anti-inflammatory, antioxidant, anti-fibrotic, and angiogenic effects. We analyzed the multi-directional effects of MSCs cultured under hypoxic conditions and their underlying mechanisms in the treatment of liver cirrhosis in a mouse model. Methods Human bone marrow-derived MSCs cultured under hypoxic (5% O2; hypoMSCs) and normoxic (21% O2; norMSCs) conditions were compared by cap analysis of gene expression (CAGE) with or without serum from liver cirrhosis patients. The therapeutic effects of MSCs, including serum liver enzyme induction, fibrosis regression, and hepatic oxidative stress, were evaluated by injecting 1 × 106, 2 × 105, or 4 × 104 MSCs/mouse into the tail veins of mice with carbon tetrachloride (CCl4)-induced liver cirrhosis. Intravital imaging was performed with a two-photon excitation microscope to confirm the various MSC migration paths to the liver. Results CAGE analysis revealed that the RNA expression levels of prostaglandin E synthase (Ptges) and miR210 were significantly higher in hypoMSCs than in norMSCs. In vivo analysis revealed that both hypoMSCs and norMSCs reduced serum alanine aminotransferase, oxidative stress, and fibrosis compared to that in control mice in a dose-dependent manner. However, hypoMSCs had stronger therapeutic effects than norMSCs. We confirmed this observation by an in vitro study in which hypoMSCs changed macrophage polarity to an anti-inflammatory phenotype via prostaglandin E2 (PGE2) stimulation. In addition, miR210 reduced the rate of hepatocyte apoptosis. Intravital imaging after MSC administration showed that both cell types were primarily trapped in the lungs. Relatively a few hypoMSCs and norMSCs migrated to the liver. There were no significant differences in their distributions. Conclusion The therapeutic effect of hypoMSCs was mediated by PGE2 and miR210 production and was greater than that of norMSCs. Therefore, MSCs can be manipulated to improve their therapeutic efficacy in the treatment of liver cirrhosis and could potentially serve in effective cell therapy. MSCs produce several factors with multidirectional effects and function as “conducting cells” in liver cirrhosis.
Highlights • HypoMSCs decreased liver damage and fibrosis in mice in a dose-dependent manner. • HypoMSCs produced more PTGES and miR-210 than norMSCs. • HypoMSCs reduced oxidative stress more effectively than norMSCs. • HypoMSCs induced anti-inflammatory macrophage growth via prostaglandin E2 production. • miR-210 reduced hepatocyte apoptosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::796000c604663d3d982bebac495f5eedTest
http://www.sciencedirect.com/science/article/pii/S2352320419300811Test

المؤلفون: Sujit Mukherjee, Evangelos Triantafyllou, Oltin T Pop, Fabien Zoulim, Enes Tunc, Alberto Quaglia, Arjuna Singanayagam, Wafa Khamri, Mark Thursz, Tie Zheng Hou, Fanny Lebossé, Julia Wendon, Rooshi Nathwani, Charalambos G. Antoniades, Cathrin Gudd, Naveenta Kumar, A. Dhar

المساهمون: Imperial College London, King‘s College London, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), Manship, Brigitte, BRC ITMAT Funding Scheme, Medical Research Council

المصدر: EBioMedicine
EBioMedicine, 2019, 49, pp.258-268. ⟨10.1016/j.ebiom.2019.10.011⟩

مصطلحات موضوعية: CHRONIC LIVER-FAILURE, 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Research paper, Transcription, Genetic, Apoptosis, Research & Experimental Medicine, CD8-Positive T-Lymphocytes, Chronic liver disease, Severity of Illness Index, 0302 clinical medicine, INFECTION, Ascites, Cytotoxic T cell, Myeloid Cells, CD8(+)T cells, ALD, alcohol-related liver disease, NEUTROPHILS, CD8(+) T cells, medicine.diagnostic_test, ACLF, acute-on-chronic-liver disease, General Medicine, Middle Aged, 3. Good health, CD8+T cells, Phenotype, Treatment Outcome, Medicine, Research & Experimental, 030220 oncology & carcinogenesis, SURVIVAL, CLD, Chronic liver disease, Female, Disease Susceptibility, medicine.symptom, Peritoneum, Life Sciences & Biomedicine, EXPRESSION, CAID, cirrhosis-associated immune dysfunction, NASH, non-alcoholic steatohepatitis, Cirrhosis-associated immune dysfunction, [SDV.CAN]Life Sciences [q-bio]/Cancer, AAH, acute alcoholic hepatitis, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, Flow cytometry, 03 medical and health sciences, Medicine, General & Internal, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, General & Internal Medicine, medicine, HV, Healthy volunteers, Humans, Aged, Cell Proliferation, Inflammation, Science & Technology, business.industry, ELD, End-stage-liver diseases, HLA-DR Antigens, medicine.disease, AD, acute decompensation, 030104 developmental biology, Immunology, Natural Killer T-Cells, business, CD8, Biomarkers, PMNs, polymorphonuclear neutrophils

الوصف: Background Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8+ T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses. Methods Sixty patients with cirrhosis were prospectively recruited for this study. CD8+ T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR+CD8+ T cells was performed using Nanostring™ technology. HLA-DR+CD8+ T cells interactions with PBMCs and myeloid cells were tested in vitro. Findings Peripheral CD8+ T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8+ T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8+ T cells. HLA-DR+CD8+ T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR+CD8+ T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR+CD8+ T cells. In comparison to their HLA-DR− counterparts, HLA-DR+CD8+ T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro. Interpretation In patients with cirrhosis, CD8+ T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID. Fund This work was supported by Medical Research Council, the Rosetrees Charitable Trust, Robert Tournut 2016 grant (Societe Nationale Francaise de GastroEnterologie), Gilead® sciences, and NIHR Imperial Biomedical Research Centre.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9318081e284f95b31ce34f205764d8dbTest
http://europepmc.org/articles/PMC6945243Test

المؤلفون: Hans-Peter Hammes, Elena Heidenreich, Peter P. Nawroth, Martina U. Muckenthaler, Sandro Altamura, Thomas Fleming, Andrea Schlotterer, Katja Müdder, Ruiyue Qiu

المصدر: Molecular Metabolism, Vol 51, Iss, Pp 101235-(2021)
Molecular Metabolism

مصطلحات موضوعية: 0301 basic medicine, Blood Glucose, Male, DR, diabetic retinopathy, Hepcidin, medicine.disease_cause, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, MetS, Metabolic Syndrome, Internal medicine, biology, Fpn, Ferroportin, Fatty liver, Liver, DIOS, dysmetabolic iron overload syndrome, CRP, C-reactive protein, Receptors, Leptin, HH, hereditary hemochromatosis, Original Article, IRP, Iron Regulatory Protein, medicine.medical_specialty, Iron Overload, Iron, 030209 endocrinology & metabolism, Mice, Transgenic, IR, Insulin Resistance, SEM, standard error of the mean, 03 medical and health sciences, Insulin resistance, ROS, reactive oxygen species, NASH, Non Alcoholic Steatohepatitis, NAFLD, medicine, Animals, Humans, Molecular Biology, business.industry, NTBI, Non Transferrin Bound Iron, Cell Biology, medicine.disease, RC31-1245, IRS1, Db/db Mouse, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, biology.protein, NAFLD, Non Alcoholic Fatty Liver Disease, Lipid Peroxidation, Steatosis, Metabolic syndrome, business, Oxidative stress, IRE, Iron Responsive Element, T2DM, Type 2 Diabetes Mellitus

الوصف: Objective The molecular pathogenesis of late complications associated with type 2 diabetes mellitus (T2DM) is not yet fully understood. While high glucose levels indicated by increased HbA1c only poorly explain disease progression and late complications, a pro-inflammatory status, oxidative stress, and reactive metabolites generated by metabolic processes were postulated to be involved. Individuals with metabolic syndrome (MetS) frequently progress to T2DM, whereby 70% of patients with T2DM show non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of MetS, and insulin resistance (IR). Epidemiological studies have shown that T2DM and steatosis are associated with alterations in iron metabolism and hepatic iron accumulation. Excess free iron triggers oxidative stress and a switch towards a macrophage pro-inflammatory status. However, so far it remains unclear whether hepatic iron accumulation plays a causative role in the generation of IR and T2DM or whether it is merely a manifestation of altered hepatic metabolism. To address this open question, we generated and characterized a mouse model of T2DM with IR, steatosis, and iron overload. Methods Leprdb/db mice hallmarked by T2DM, IR and steatosis were crossed with Fpnwt/C326S mice with systemic iron overload to generate Leprdb/db/Fpnwt/C326S mice. The resulting progeny was characterized for major diabetic and iron-related parameters. Results We demonstrated that features associated with T2DM in Leprdb/db mice, such as obesity, steatosis, or IR, reduce the degree of tissue iron overload in Fpnwt/C326S mice, suggesting an ‘iron resistance’ phenotype. Conversely, we observed increased serum iron levels that strongly exceeded those in the iron-overloaded Fpnwt/C326S mice. Increased hepatic iron levels induced oxidative stress and lipid peroxidation and aggravated IR, as indicated by diminished IRS1 phosphorylation and AKT activation. Additionally, in the liver, we observed gene response patterns indicative of de novo lipogenesis and increased gluconeogenesis as well as elevated free glucose levels. Finally, we showed that iron overload in Leprdb/db/Fpnwt/C326S mice enhances microvascular complications observed in retinopathy, suggesting that iron accumulation can enhance diabetic late complications associated with the liver and the eye. Conclusion Taken together, our data show that iron causes the worsening of symptoms associated with the MetS and T2DM. These findings imply that iron depletion strategies together with anti-diabetic drugs may ameliorate IR and diabetic late complications.
Highlights • T2DM causes an iron resistance phenotype. • Iron affects hepatic insulin resistance. • Systemic iron accumulation aggravates diabetic pericyte loss.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::746ad7abfa625d87337f2502f8e59462Test
http://www.sciencedirect.com/science/article/pii/S2212877821000806Test

المؤلفون: N. Thao N. Galvan, Mercedes Barzi, John A. Goss, William R. Lagor, David D. Moore, Adam Dean, Neil J. McKenna, Pavel Sumazin, Barry Zorman, Diane Yang, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Xavier Legras, David E. Cohen, Robert Brian York, Malgorzata Borowiak, Michele Alves-Bezerra, Scott A. Ochsner

المصدر: JHEP reports : innovation in hepatology, vol 3, iss 3
JHEP Reports
JHEP Reports, Vol 3, Iss 3, Pp 100281-(2021)

مصطلحات موضوعية: phosphatidylinositol, Cirrhosis, Steatosis, ALT, hexosylceramide, Humanised mice, SREBP, sterol regulatory element-binding protein, PI, RC799-869, CMHs, chimeric mouse hepatocytes, 0302 clinical medicine, GGT, gamma-glutamyl transpeptidase, aspartate aminotransferase, HCC, gamma-glutamyl transpeptidase, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, Western-type diet, Gastroenterology, NASH, CHHs, Diseases of the digestive system. Gastroenterology, 3. Good health, confidence transcript, HCT, cholesteryl ester, human albumin, DCER, dihydroceramide, 030211 gastroenterology & hepatology, PC, non-alcoholic steatohepatitis, PE, transgene-free Il2rg-/-/Rag2-/-/Fah, free fatty acid, LPE, lysophosphatidylethanolamine, DCER, NASH, non-alcoholic steatohepatitis, HCER, hexosylceramide, NC, normal chow, TIRF, PE, phosphatidylethanolamine, nitisinone, lysophosphatidylethanolamine, 03 medical and health sciences, dihydroceramide, Human disease modelling, NAFLD, FFA, free fatty acid, LCER, DEG, MUFA, education, phosphatidylcholine, chimeric mouse hepatocytes, FAH, SM, sphingomyelin, ALP, alkaline phosphatase, FA, fatty acid, NTBC, Fatty acid, medicine.disease, differentially expressed gene, lactosylceramide, PNPLA3, patatin-like-phospholipase domain-containing protein 3, Lipid metabolism, chemistry, fatty acid, PUFA, hALB, human albumin, TIRF, transgene-free Il2rg-/-/Rag2-/-/Fah, AST, aspartate aminotransferase, CT, confidence transcript, PC, phosphatidylcholine, monounsaturated fatty acid, DEG, differentially expressed gene, MUFA, monounsaturated fatty acid, Immunology and Allergy, MAG, monoacylglycerol, PUFA, polyunsaturated free FA, CE, cholesteryl ester, CER, diacylglycerol, FAH, fumarylacetoacetate hydrolase, Fatty liver, SM, chimeric human hepatocytes, hepatocellular carcinoma, CBPEGs, cholesterol biosynthesis pathway enzyme genes, CE, MAG, LPC, patatin-like-phospholipase domain-containing protein 3, triacylglycerol, LPE, alkaline phosphatase, sterol regulatory element-binding protein, Polyunsaturated fatty acid, Research Article, CT, NAFLD, non-alcoholic fatty liver disease, FA, HCER, TAG, triacylglycerol, fumarylacetoacetate hydrolase, monoacylglycerol, alanine aminotransferase, Population, cholesterol biosynthesis pathway enzyme genes, Biology, SREBP, PI, phosphatidylinositol, sphingomyelin, lysophosphatidylcholine, WD, ALT, alanine aminotransferase, high confidence transcriptional target, Internal Medicine, medicine, CBPEGs, ceramide, hALB, LCER, lactosylceramide, normal chow, AST, polyunsaturated free FA, WD, Western-type diet, PNPLA3, 030304 developmental biology, Hepatitis, LPC, lysophosphatidylcholine, Hepatology, DAG, non-alcoholic fatty liver disease, NTBC, nitisinone, CMHs, GGT, HCT, high confidence transcriptional target, phosphatidylethanolamine, TAG, Cancer research, CHHs, chimeric human hepatocytes, ALP, Liver function, NC, CER, ceramide, HCC, hepatocellular carcinoma, FFA, DAG, diacylglycerol, Non-alcoholic fatty liver disease

الوصف: Background & Aims The accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world’s population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model. Methods We generated TIRF (transgene-free Il2rg-/-/Rag2-/-/Fah-/-) mice, populated their livers with human hepatocytes, and fed them a Western-type diet for 12 weeks. Results Within the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis. Conclusions These NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis. Lay summary Fatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in humans with fatty liver. This novel humanised mouse system can be used to study human fatty liver disease.
Graphical abstract
Highlights • Human liver chimeric mice fed a western diet develop NAFLD. • Within the same chimeric liver, human hepatocytes developed pronounced steatosis while murine hepatocytes remained normal. • Unbiased metabolomics and lipidomics of fatty humanised mouse livers revealed signatures of clinical NAFLD. • Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes. • This humanised NAFLD model is a physiologically relevant, experimentally tractable model for the study of steatosis.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52b0393a5555874a5526c491b8421dfdTest
https://escholarship.org/uc/item/2hg8h2x9Test

المؤلفون: Valentin A. Pavlov

المصدر: Pharmacology & Therapeutics

مصطلحات موضوعية: 0301 basic medicine, ChAT, choline acetyltransferase, BMI, body mass index, Inflammatory reflex, NLRP3, NLRs nucleotide-binding oligomerization domain (NOD)-like receptors nucleotide-binding oligomerization domain-like receptor family pyrin domain containing-3, Type 2 diabetes, Disease, Bioinformatics, 0302 clinical medicine, AChE, acetylcholinesterase, Medicine, Pharmacology (medical), TLR, toll-like receptors, NF-κB, nuclear factor kappa B, COVID-19, coronavirus disease 2019, TNF, tumor necrosis factor, IBD, inflammatory bowel disease, HDL-C, high density lipoprotein-cholesterol, Vagus Nerve, GI, gastrointestinal, Metabolic syndrome, ICU, intensive care unit, Bioelectronic medicine, VNS, vagus nerve stimulation, 030220 oncology & carcinogenesis, LPS, lipopolysaccharide, MetS, metabolic syndrome, medicine.symptom, SARS-CoV, severe acute respiratory syndrome CoV, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, α7nAChR, alpha 7 nicotinic acetylcholine receptor, Inflammation, HRV, heart rate variability, Article, 03 medical and health sciences, NTS, nucleus tractus solitarius, Immune system, DMN, dorsal motor nucleus of the vagus, Humans, Obesity, mAChR, muscarinic acetylcholine receptor, ARDS, acute respiratory distress syndrome, Pharmacology, SARS-CoV-2, ACh, acetylcholine, business.industry, COVID-19, medicine.disease, NA, nucleus ambiguus, IL, interleukin, Vagus nerve, The inflammatory reflex, 030104 developmental biology, MERS-CoV, Middle East respiratory syndrome corona virus, JAK2/STAT3, Janus kinase 2/signal transducer and activator of transcription 3, business, SARS-CoV-2, severe acute respiratory syndrome coronavirus-2

الوصف: Obesity and the metabolic syndrome (MetS), which have reached pandemic proportions significantly increase the risk for type 2 diabetes, cardiovascular disease, and other serious conditions. Recent data with COVID-19 patients indicate that obesity also is a significant risk factor for this novel viral disease and poor outcome of associated critical illness. These findings considerably change the view of obesity as a driver of serious, but slowly-progressing chronic diseases, and emphasize the urgency to explore new therapeutic approaches. Inflammation is a recognized driver of metabolic derangements in obesity and MetS, and a core feature of COVID-19 pathobiology. Recent advances in our understanding of inflammatory regulation have highlighted the role of the nervous system and the vagus nerve-based inflammatory reflex. Current bioelectronic and pharmacological therapeutic explorations centered on the inflammatory reflex offer new approaches for conditions characterized by immune and metabolic dysregulation and for ameliorating the escalating burden of obesity, MetS, and COVID-19.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2e3679f48f885bb324216f0c362acfbTest