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Article ; Online: Increased TLR/MyD88 signaling in patients with obesity: is there a link to COVID-19 disease severity?

Cuevas, Ada M / Clark, Jeanne M / Potter, James J

International journal of obesity (2005)

2021 Volume 45, Issue 5, Page(s) 1152–1154

Abstract: COVID-19 is a pandemic disease caused by a coronavirus, designed as SARS CoV-2, whose clinical presentation is widely variable, with most patients having mild or no symptoms, but others developing a malign disease with multi-organ failure and even death. ...

Abstract	COVID-19 is a pandemic disease caused by a coronavirus, designed as SARS CoV-2, whose clinical presentation is widely variable, with most patients having mild or no symptoms, but others developing a malign disease with multi-organ failure and even death. Accumulating data from different populations have shown that obesity is a risk factor for a severe evolution of the disease, however, the mechanisms that explain this association are not clearly understood. An ominous evolution of COVID-19 has been attributed to an exacerbated inflammatory response, designed as "cytokine storm" with augmented production of cytokines/chemokines through the activation of toll-like receptors (TLR) by pathogen-associated molecular patterns, that triggers an inflammatory downstream response, mediated in part by the adaptor molecule, myeloid differentiation factor 88 (MyD88). Previous studies have reported an increased expression of MyD88 and TLRs in people with obesity, mainly in those with metabolic complications. Therefore, we hypothesize, that an underlying increased Myd88/TLR signaling may predispose to patients with obesity to develop an exaggerated and dangerous inflammatory reaction against SARS CoV-2 infection, explaining at least in part, the higher severity of COVID-19. In addition, MyD88/TLR signaling in people with obesity could have a role in the development of several chronic diseases.
MeSH term(s)	COVID-19/complications ; COVID-19/immunology ; COVID-19/physiopathology ; Cytokine Release Syndrome/immunology ; Humans ; Myeloid Differentiation Factor 88/metabolism ; Obesity/complications ; Obesity/immunology ; Obesity/physiopathology ; Pandemics ; Risk Factors ; SARS-CoV-2 ; Signal Transduction/immunology ; Toll-Like Receptors/metabolism
Chemical Substances	MYD88 protein, human ; Myeloid Differentiation Factor 88 ; Toll-Like Receptors
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-021-00768-8
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Article ; Online: Impact of nonalcoholic fatty liver disease on clinical outcomes in patients with COVID-19 among persons living with HIV: A multicenter research network study.

Krishnan, Arunkumar / Woreta, Tinsay A / Sims, Omar T / Hamilton, James P / Potter, James J / Alqahtani, Saleh A

Journal of infection and public health

2023 Volume 16, Issue 5, Page(s) 673–679

Abstract: Background: People living with human immunodeficiency virus (PLWH) are at an increased risk of nonalcoholic fatty liver disease (NAFLD) but how these patients react to COVID-19 infection is unclear. We examined the clinical characteristics and outcomes ... ...

Abstract	Background: People living with human immunodeficiency virus (PLWH) are at an increased risk of nonalcoholic fatty liver disease (NAFLD) but how these patients react to COVID-19 infection is unclear. We examined the clinical characteristics and outcomes of patients with and without nonalcoholic fatty liver disease (NAFLD) among people living with human immunodeficiency virus (PLWH) diagnosed with COVID-19. Methods: A multicenter, retrospective cohort study was conducted using TriNetX. Participants diagnosed with COVID-19 between January 20, 2020, and October 31, 2021, in PLWH were identified and divided into cohorts based on preexisting NAFLD. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization, severe disease, critical care, need for mechanical ventilation, and acute kidney injury(AKI). Propensity score matching (PSM) mitigated the imbalance among group covariates. Risk ratios (RR) with 95 % confidence intervals (CI) were calculated. Results: Of the 5012 PLWH identified with confirmed COVID-19 during the study period, 563 had a diagnosis of NAFLD. After PSM, both groups were well-matched with 561 patients. The primary outcome did not differ between the cohorts at 30-days, even after a fully adjusted analysis, and the risk of all-cause mortality did not differ at 60 and 90 days. NAFLD had a significantly higher risk for hospitalization rates (RR 1.32; 95 % CI, 1.06-1.63) and AKI (RR 2.55; 95 % CI 1.42-4.57) than the non-NAFLD group at 30 days. No other differences were detected in other secondary outcome measures. Conclusions: Preexisting NAFLD is associated with an increased risk for hospitalization and AKI among PLWH infected with COVID-19. The potential role of NAFLD in developing severe COVID-19 among PLWH remains to be elucidated in future studies. Still, this study indicates the need for careful monitoring of this at-risk population.
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/epidemiology ; COVID-19/complications ; COVID-19/therapy ; HIV ; Retrospective Studies ; HIV Infections/complications ; HIV Infections/epidemiology
Language	English
Publishing date	2023-02-13
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2023.02.008
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Article: Effects of input shaping on manual control of flexible and time-delayed systems.

Potter, James J / Singhose, William E

Human factors

2015 Volume 56, Issue 7, Page(s) 1284–1295

Abstract: Objective: The objective was to study the performance of a manual tracking task with system flexibility and time delays in the input channel and to examine the effects of input shaping the human operator's commands.: Background: It has long been ... ...

Abstract	Objective: The objective was to study the performance of a manual tracking task with system flexibility and time delays in the input channel and to examine the effects of input shaping the human operator's commands. Background: It has long been known that low-frequency, lightly damped vibration hinders performance of a manually controlled system. Recently, input shaping has been shown to improve the performance of such systems in a compensatory-display tracking task. It is unknown if similar improvements are seen with pursuit-display tasks, or how the improvement changes when time delays are added to the system. Method: A total of 18 novice participants performed a pursuit-view tracking experiment with a spring-centered joystick. Controlled elements included an integrator, an integrator with a lightly damped flexible mode, and an input-shaped integrator with a flexible mode. The input to these controlled elements was delayed between 0 and 1 s. Tracking performance was quantified by root mean square tracking error, and subjective difficulty was quantified by ratings on a Cooper-Harper scale. Results: Performance was best with the undelayed integrator. Both time delay and flexibility degraded performance. Input shaping improved control of the flexible element, with a diminishing benefit as the time delay increased. Tracking error and subjective rating were significantly related. Some operators used a pulsive control strategy. Conclusion: Input shaping can improve the performance of a manually controlled system with flexibility, even when time delays are present. Application: This study is useful to designers of human-controlled systems, especially those with problematic flexibility and/or time delays.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Task Performance and Analysis ; Vibration ; Young Adult
Language	English
Publishing date	2015-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	212725-8
ISSN	1547-8181 ; 0018-7208
ISSN (online)	1547-8181
ISSN	0018-7208
DOI	10.1177/0018720814528004
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Article: Malnutrition Increases Hospital Length of Stay and Mortality among Adult Inpatients with COVID-19

Vong, Tyrus / Yanek, Lisa R. / Wang, Lin / Yu, Huimin / Fan, Christopher / Zhou, Elinor / Oh, Sun Jung / Szvarca, Daniel / Kim, Ahyoung / Potter, James J. / Mullin, Gerard E.

Nutrients. 2022 Mar. 21, v. 14, no. 6

2022

Abstract: Background: Malnutrition has been linked to adverse health economic outcomes. There is a paucity of data on malnutrition in patients admitted with COVID-19. Methods: This is a retrospective cohort study consisting of 4311 COVID-19 adult (18 years and ... ...

Abstract	Background: Malnutrition has been linked to adverse health economic outcomes. There is a paucity of data on malnutrition in patients admitted with COVID-19. Methods: This is a retrospective cohort study consisting of 4311 COVID-19 adult (18 years and older) inpatients at 5 Johns Hopkins-affiliated hospitals between 1 March and 3 December 2020. Malnourishment was identified using the malnutrition universal screening tool (MUST), then confirmed by registered dietitians. Statistics were conducted with SAS v9.4 (Cary, NC, USA) software to examine the effect of malnutrition on mortality and hospital length of stay among COVID-19 inpatient encounters, while accounting for possible covariates in regression analysis predicting mortality or the log-transformed length of stay. Results: COVID-19 patients who were older, male, or had lower BMIs had a higher likelihood of mortality. Patients with malnutrition were 76% more likely to have mortality (p < 0.001) and to have a 105% longer hospital length of stay (p < 0.001). Overall, 12.9% (555/4311) of adult COVID-19 patients were diagnosed with malnutrition and were associated with an 87.9% increase in hospital length of stay (p < 0.001). Conclusions: In a cohort of COVID-19 adult inpatients, malnutrition was associated with a higher likelihood of mortality and increased hospital length of stay.
Keywords	COVID-19 infection ; adults ; cohort studies ; computer software ; hospitals ; males ; malnutrition ; mortality ; regression analysis
Language	English
Dates of publication	2022-0321
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14061310
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Article ; Online: Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients.

Krishnan, Arunkumar / Prichett, Laura / Tao, Xueting / Alqahtani, Saleh A / Hamilton, James P / Mezey, Esteban / Strauss, Alexandra T / Kim, Ahyoung / Potter, James J / Chen, Po-Hung / Woreta, Tinsay A

World journal of gastroenterology

2022 Volume 28, Issue 5, Page(s) 570–587

Abstract: Background: Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood.: Aim: We aimed ... ...

Abstract	Background: Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood. Aim: We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality. Methods: This retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis. Results: A total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilation. Conclusion: Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient's severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.
MeSH term(s)	Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Baltimore ; Bilirubin ; COVID-19/diagnosis ; COVID-19/therapy ; Hospitalization ; Humans ; Liver/chemistry ; Retrospective Studies ; Severity of Illness Index
Chemical Substances	Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Alkaline Phosphatase (EC 3.1.3.1) ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v28.i5.570
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Article ; Online: Malnutrition Increases Hospital Length of Stay and Mortality among Adult Inpatients with COVID-19.

Vong, Tyrus / Yanek, Lisa R / Wang, Lin / Yu, Huimin / Fan, Christopher / Zhou, Elinor / Oh, Sun Jung / Szvarca, Daniel / Kim, Ahyoung / Potter, James J / Mullin, Gerard E

Nutrients

2022 Volume 14, Issue 6

Abstract	Background: Malnutrition has been linked to adverse health economic outcomes. There is a paucity of data on malnutrition in patients admitted with COVID-19. Methods: This is a retrospective cohort study consisting of 4311 COVID-19 adult (18 years and older) inpatients at 5 Johns Hopkins-affiliated hospitals between 1 March and 3 December 2020. Malnourishment was identified using the malnutrition universal screening tool (MUST), then confirmed by registered dietitians. Statistics were conducted with SAS v9.4 (Cary, NC, USA) software to examine the effect of malnutrition on mortality and hospital length of stay among COVID-19 inpatient encounters, while accounting for possible covariates in regression analysis predicting mortality or the log-transformed length of stay. Results: COVID-19 patients who were older, male, or had lower BMIs had a higher likelihood of mortality. Patients with malnutrition were 76% more likely to have mortality (p < 0.001) and to have a 105% longer hospital length of stay (p < 0.001). Overall, 12.9% (555/4311) of adult COVID-19 patients were diagnosed with malnutrition and were associated with an 87.9% increase in hospital length of stay (p < 0.001). Conclusions: In a cohort of COVID-19 adult inpatients, malnutrition was associated with a higher likelihood of mortality and increased hospital length of stay.
MeSH term(s)	Adult ; COVID-19 ; Hospitals ; Humans ; Inpatients ; Length of Stay ; Male ; Malnutrition/diagnosis ; Retrospective Studies
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14061310
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Article ; Online: Changes in Gut Microbiome after Bariatric Surgery Versus Medical Weight Loss in a Pilot Randomized Trial.

Lee, Clare J / Florea, Liliana / Sears, Cynthia L / Maruthur, Nisa / Potter, James J / Schweitzer, Michael / Magnuson, Thomas / Clark, Jeanne M

Obesity surgery

2019 Volume 29, Issue 10, Page(s) 3239–3245

Abstract: Background: Gut microbiota likely impact obesity and metabolic diseases. We evaluated the changes in gut microbiota after surgical versus medical weight loss in adults with diabetes and obesity.: Methods: We performed 16S rRNA amplicon sequencing to ... ...

Abstract	Background: Gut microbiota likely impact obesity and metabolic diseases. We evaluated the changes in gut microbiota after surgical versus medical weight loss in adults with diabetes and obesity. Methods: We performed 16S rRNA amplicon sequencing to identify the gut microbial composition at baseline and at 10% weight loss in adults with diabetes who were randomized to medical weight loss (MWL, n = 4), adjustable gastric banding (AGB, n = 4), or Roux-en-Y gastric bypass (RYGB, n = 4). Results: All participants were female, 75% reported black race with mean age of 51 years. At similar weight loss amount and glycemic improvement, the RYGB group had the most number of bacterial species (10 increased, 1 decreased) that significantly changed (p < 0.05) in relative abundance. Alpha-diversity at follow-up was significantly lower in AGB group compared to MWL and RYGB (observed species for AGB vs. MWL, p = 0.0093; AGB vs. RYGB, p = 0.0093). The relative abundance of Faecalibacterium prausnitzii increased in 3 participants after RYGB, 1 after AGB, and 1 after MWL. Conclusions: At similar weight loss and glycemic improvement, the greatest alteration in gut microbiota occurred after RYGB with an increase in the potentially beneficial bacterium, F. prausnitzii. Gut microbial diversity tended to decrease after AGB and increase after RYGB and MWL. Future studies are needed to determine the impact and durability of gut microbial changes over time and their role in long-term metabolic improvement after bariatric surgery in adults with type 2 diabetes. Clinical trial registration: NCTDK089557- ClinicalTrials.gov.
MeSH term(s)	Adult ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; Bacterial Typing Techniques ; Bariatric Surgery/methods ; Biodiversity ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/microbiology ; Diabetes Mellitus, Type 2/surgery ; Feces/microbiology ; Female ; Gastric Bypass ; Gastrointestinal Microbiome/physiology ; Gastroplasty ; Humans ; Middle Aged ; Obesity/blood ; Obesity/microbiology ; Obesity/surgery ; Obesity, Morbid/blood ; Obesity, Morbid/microbiology ; Obesity, Morbid/surgery ; Pilot Projects ; Postoperative Period ; RNA, Ribosomal, 16S/genetics ; Weight Loss/physiology
Chemical Substances	Blood Glucose ; RNA, Ribosomal, 16S
Language	English
Publishing date	2019-06-30
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-019-03976-4
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Article ; Online: Acetaldehyde increases endogenous adiponectin and fibrogenesis in hepatic stellate cells but exogenous adiponectin inhibits fibrogenesis.

Potter, James J / Mezey, Esteban

Alcoholism, clinical and experimental research

2007 Volume 31, Issue 12, Page(s) 2092–2100

Abstract: Background: Adiponectin has antifibrogenic properties. Acetaldehyde, the principal metabolite of ethanol, is known to stimulate the expression of type I collagen genes and the production of type I collagen by wild-type (wt) but not by obese gene (ob/ob) ...

Abstract	Background: Adiponectin has antifibrogenic properties. Acetaldehyde, the principal metabolite of ethanol, is known to stimulate the expression of type I collagen genes and the production of type I collagen by wild-type (wt) but not by obese gene (ob/ob) stellate cells. The aim of this study was to determine the expression of adiponectin in activated stellate cells obtained from wt and ob/ob mice and to determine the effects of acetaldehyde on adiponectin in relation to the expression of type I collagen. Methods: Stellate cells were isolated from wt and ob/ob mice by perfusion of the portal vein and cultured. Cell adiponectin was visualized by immunohistochemistry and confocal microscopy and determined by radioimmunoassay and by western blot. Adiponectin mRNA and alpha(1)(I) collagen mRNA were determined by quantitative real time polymerase chain reaction. Results: Adiponectin levels were similar in wt and ob/ob stellate cells. Adiponectin receptor 2 mRNA (AdipoR2 mRNA) and AdipoR2 immunoprotein were higher in ob/ob than in wt stellate cells (p < 0.01). Acetaldehyde (200 microM) increased adiponectin both in wt and in ob/ob stellate cells (p < 0.05), but increased AdipoR2 immunoprotein only in ob/ob stellate cells (p < 0.01). However, in the presence of leptin, acetaldehyde decreased adiponectin in ob/ob stellate cells (p < 0.01). Acetaldehyde enhanced alpha(1)(I) collagen mRNA in wt (p < 0.05), but decreased it in ob/ob stellate cells (p < 0.01). Leptin abrogated the effect of acetaldehyde in decreasing alpha(1)(I) collagen mRNA in ob/ob stellate cells (p < 0.01). Adiponectin inhibited alpha(1)(I) collagen mRNA in the basal state in wt stellate cells or when enhanced by acetaldehyde. Conclusions: Adiponectin and adiponectin receptor are present in activated stellate cells. Adiponectin has a negative regulatory role on the enhancing effect of acetaldehyde on fibrogenesis in alcoholic liver disease.
MeSH term(s)	Acetaldehyde/antagonists & inhibitors ; Acetaldehyde/pharmacology ; Adiponectin/genetics ; Adiponectin/pharmacology ; Animals ; Blotting, Western ; Cells, Cultured ; Collagen Type I/genetics ; Drug Interactions ; Fibrosis/pathology ; Gene Expression/drug effects ; Hepatocytes/drug effects ; Hepatocytes/pathology ; Liver/drug effects ; Liver/pathology ; Liver Cirrhosis/chemically induced ; Liver Cirrhosis/pathology ; Liver Cirrhosis/prevention & control ; Male ; Mice ; Mice, Obese ; Microscopy, Confocal ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Radioimmunoassay ; Receptors, Adiponectin/drug effects ; Receptors, Adiponectin/genetics
Chemical Substances	Adiponectin ; Collagen Type I ; RNA, Messenger ; Receptors, Adiponectin ; adiponectin receptor 1, mouse ; Acetaldehyde (GO1N1ZPR3B)
Language	English
Publishing date	2007-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2007.00529.x
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Article ; Online: The combination of selenium and vitamin E inhibits type I collagen formation in cultured hepatic stellate cells.

Mezey, Esteban / Liu, Xiaopu / Potter, James J

Biological trace element research

2011 Volume 140, Issue 1, Page(s) 82–94

Abstract: This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without ... ...

Abstract	This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α(1)(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
MeSH term(s)	Cells, Cultured ; Collagen Type I/antagonists & inhibitors ; Collagen Type I/biosynthesis ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Humans ; Procollagen/antagonists & inhibitors ; Procollagen/biosynthesis ; Sodium Selenite/pharmacology ; Structure-Activity Relationship ; Vitamin E/pharmacology
Chemical Substances	Collagen Type I ; Procollagen ; Vitamin E (1406-18-4) ; Sodium Selenite (HIW548RQ3W)
Language	English
Publishing date	2011-04
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-010-8672-7
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Article: The Combination of Selenium and Vitamin E Inhibits Type I Collagen Formation in Cultured Hepatic Stellate Cells

Mezey, Esteban / Liu, Xiaopu / Potter, James J

Biological trace element research.. 2011 Apr., v. 140, no. 1

2011

Abstract	This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α1(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
Keywords	antioxidant activity ; apoptosis ; collagen ; crosslinking ; cultured cells ; fibrosis ; humans ; lead ; lipid peroxidation ; messenger RNA ; protective effect ; protein-glutamine gamma-glutamyltransferase ; secretion ; selenium ; sodium selenite ; transforming growth factors ; vitamin E
Language	English
Dates of publication	2011-04
Size	p. 82-94.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-010-8672-7
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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito