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2.
Cell Death Dis ; 12(1): 25, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414395

RESUMO

The human leukocyte antigen F-associated transcript 10 (FAT10) is a member of the small ubiquitin-like protein family that binds to its target proteins and subjects them to degradation by the ubiquitin-proteasome system (UPS). In the heart, FAT10 plays a cardioprotective role and affects predisposition to cardiac arrhythmias after myocardial ischemia (MI). However, whether and how FAT10 influences cardiac arrhythmias is unknown. We investigated the role of FAT10 in regulating the sodium channel Nav1.5, a major regulator of cardiac arrhythmias. Fat10 was conditionally deleted in cardiac myocytes using Myh6-Cre and Fat10F/F mice (cFat10-/-). Compared with their wild-type littermates, cFat10-/- mice showed prolonged RR, PR, and corrected QT (QTc) intervals, were more likely to develop ventricular arrhythmia, and had increased mortality after MI. Patch-clamp studies showed that the peak Na+ current was reduced, and the late Na+ current was significantly augmented, resulting in a decreased action potential amplitude and delayed depolarization. Immunoblot and immunofluorescence analyses showed that the expression of the membrane protein Nav1.5 was decreased. Coimmunoprecipitation experiments demonstrated that FAT10 stabilized Nav1.5 expression by antagonizing Nav1.5 ubiquitination and degradation. Specifically, FAT10 bound to the lysine residues in the C-terminal fragments of Nav1.5 and decreased the binding of Nav1.5 to the Nedd4-2 protein, a ubiquitin E3 ligase, preventing degradation of the Nav1.5 protein. Collectively, our findings showed that deletion of the Fat10 in cardiac myocytes led to increased cardiac arrhythmias and increased mortality after MI. Thus, FAT10 protects against ischemia-induced ventricular arrhythmia by binding to Nav1.5 and preventing its Neddylation and degradation by the UPS after MI.

3.
Adv Mater ; : e2007497, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33448064

RESUMO

Owing to their high safety and reversibility, aqueous microbatteries using zinc anodes and an acid electrolyte have emerged as promising candidates for wearable electronics. However, a critical limitation that prevents implementing zinc chemistry at the microscale lies in its spontaneous corrosion in an acidic electrolyte that causes a capacity loss of 40% after a ten-hour rest. Widespread anti-corrosion techniques, such as polymer coating, often retard the kinetics of zinc plating/stripping and lack spatial control at the microscale. Here, a polyimide coating that resolves this dilemma is reported. The coating prevents corrosion and hence reduces the capacity loss of a standby microbattery to 10%. The coordination of carbonyl oxygen in the polyimide with zinc ions builds up over cycling, creating a zinc blanket that minimizes the concentration gradient through the electrode/electrolyte interface and thus allows for fast kinetics and low plating/stripping overpotential. The polyimide's patternable feature energizes microbatteries in both aqueous and hydrogel electrolytes, delivering a supercapacitor-level rate performance and 400 stable cycles in the hydrogel electrolyte. Moreover, the microbattery is able to be attached to human skin and offers strong resistance to deformations, splashing, and external shock. The skin-mountable microbattery demonstrates an excellent combination of anti-corrosion, reversibility, and durability in wearables.

4.
Funct Integr Genomics ; 21(1): 125-138, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33415515

RESUMO

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). Nevertheless, the mechanism and regulatory network associated with this process remain largely unknown. In this study, we performed a comprehensive analysis of the expression of mRNAs, lncRNAs, and circRNAs by RNA-seq. A total of 3265 mRNAs, 1084 lncRNAs, and 38 circRNAs were found to be differentially expressed. Among these, 269 mRNAs were found to encode transcription factors (TFs). Functional enrichment analysis indicated that the dysregulated TFs are associated with the Hedgehog, Jak-STAT, TGF-beta, and MAPK signaling pathways. Furthermore, we constructed co-expression networks to screen the core lncRNAs and circRNAs involved in the regulation of transcription factors in these four pathways. Finally, we constructed a competing endogenous RNA (ceRNA) network of ESCC based on the abovementioned pathways. Our findings provide important insight into the role of lncRNAs and circRNAs in ESCC; the differentially expressed lncRNAs and circRNAs may represent potential targets for ESCC diagnosis and therapy.

5.
J Mol Cell Cardiol ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33307094

RESUMO

Autophagy plays a deleterious role in ischemic myocardial injury. The deacetylase SIRT1 is a well-established regulator of autophagy that can be modified by the ubiquitin-like protein SUMO1. Our previous work demonstrated that another ubiquitin-like protein, FAT10, exerts cardioprotective effects against myocardial ischemia by stabilizing the caveolin-3 protein; however, the effects of FAT10 on autophagy through SIRT1 are unclear. Here, we constructed a Fat10-knockout rat model to evaluate the role of FAT10 in autophagy. In vivo and in vitro assays confirmed that FAT10 suppressed autophagy to protect the heart from ischemic myocardial injury. Mechanistically, FAT10 was mainly involved in the regulation of the autophagosome formation process. FAT10 affected autophagy through modulating SIRT1 degradation, which resulted in reduced SIRT1 nuclear translocation and inhibited SIRT1 activity via its C-terminal glycine residues. Notably, FAT10 competed with SUMO1 at the K734 modification site of SIRT1, which further reduced LC3 deacetylation and suppressed autophagy. Our findings suggest that FAT10 inhibits autophagy by antagonizing SIRT1 SUMOylation to protect the heart from ischemic myocardial injury. This is a novel mechanism through which FAT10 regulates autophagy as a cardiac protector.

6.
World J Gastrointest Oncol ; 12(11): 1272-1287, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33250960

RESUMO

BACKGROUND: Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer. AIM: To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism. METHODS: We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed. RESULTS: C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis. CONCLUSION: C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.

7.
Liver Transpl ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217178

RESUMO

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well-characterized. Here, we describe renal function and characteristics associated with renal dysfunction at 30-days post-TIPS. METHODS: Adults with cirrhosis who underwent TIPS at nine hospitals in the US 2010-2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤ -15ml/min/1.73m2 and eGFR ≤ 60ml/min/1.73m2 , or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. RESULTS: Of 673 patients: median age 57 years, 38% female, 26% had diabetes, median MELDNa 17. Thirty days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared to those with stable renal function, were more likely to have NAFLD (33% versus 17%, p = 0.01) and comorbid diabetes (42% versus 24%, p < 0.01). Multivariate logistic regressions showed NAFLD (OR 2.04, 95%CI 1.00 to 4.17, p = 0.05), serum sodium (OR 1.06 per mEq/L, 95%CI 1.01 to 1.12, p = 0.03), and diabetes (OR 2.04, 95%CI 1.16 to 3.61, p = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed those with post-TIPS renal dysfunction were at higher sub-hazard of death (sHR 1.74, 95%CI 1.18 to 2.56, p = 0.01). CONCLUSIONS: In this large multi-center cohort, we found NAFLD, diabetes, and baseline serum sodium associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities prior to proceeding with the procedure.

8.
Pharmacol Res ; : 105286, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157234

RESUMO

Alcohol consumption is one of the risk factors for kidney injury. The underlying mechanism of alcohol-induced kidney injury remains largely unknown. We previously found that the kidney in a mouse model of alcoholic kidney injury had severe inflammation. In this study, we found that the administration of alcohol was associated with the activation of NLRP3 inflammasomes and NF-κB signaling, and the production of pro-inflammatory cytokines. Whole-genome methylation sequencing (WGBS) showed that the DNA encoding fat mass and obesity-associated protein (FTO) was significantly methylated in the alcoholic kidney. This finding was confirmed with the bisulfite sequencing (BSP), which showed that alcohol increased DNA methylation of FTO in the kidney. Furthermore, inhibition of DNA methyltransferases (DNMTs) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified peroxisome proliferator activated receptor-α (PPAR-α) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-α m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-κB-driven renal inflammation in the kidney. These findings may provide novel strategies for preventing and treating alcoholic kidney diseases.

9.
Adv Sci (Weinh) ; 7(19): 2001561, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33042763

RESUMO

High performance, flexibility, safety, and robust integration for micro-supercapacitors (MSCs) are of immense interest for the urgent demand for miniaturized, smart energy-storage devices. However, repetitive photolithography processes in the fabrication of on-chip electronic components including various photoresists, masks, and toxic etchants are often not well-suited for industrial production. Here, a cost-effective stamping strategy is developed for scalable and rapid preparation of graphene-based planar MSCs. Combining stamps with desired shapes and highly conductive graphene inks, flexible MSCs with controlled structures are prepared on arbitrary substrates without any metal current collectors, additives, and polymer binders. The interdigitated MSC exhibits high areal capacitance up to 21.7 mF cm-2 at a current of 0.5 mA and a high power density of 6 mW cm-2 at an energy density of 5 µWh cm-2. Moreover, the MSCs show outstanding cycling performance and remarkable flexibility over 10 000 charge-discharge cycles and 300 bending cycles. In addition, the capacitance and output voltage of the MSCs are easily adjustable through interconnection with well-defined arrangements. The efficient, rapid manufacturing of the graphene-based interdigital MSCs with outstanding flexibility, shape diversity, and high areal capacitance shows great potential in wearable and portable electronics.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32927050

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 U.S. medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; p<0.001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; p<0.001). CONCLUSION: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

11.
Front Cell Dev Biol ; 8: 837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974354

RESUMO

The reproductive altruism in social insects is an evolutionary enigma that has been puzzling scientists starting from Darwin. Unraveling how reproductive skew emerges and maintains is crucial to understand the reproductive altruism involved in the consequent division of labor. The regulation of adult worker reproduction involves conspecific inhibitory signals, which are thought to be chemical signals by numerous studies. Despite the primary identification of few chemical ligands, the action modes of primer pheromones that regulate reproduction and their molecular causes and effects remain challenging. Here, these questions were elucidated by comprehensively reviewing recent advances. The coordination with other modalities of queen pheromones (QPs) and its context-dependent manner to suppress worker reproduction were discussed under the vast variation and plasticity of reproduction during colony development and across taxa. In addition to the effect of QPs, special attention was paid to recent studies revealing the regulatory effect of brood pheromones. Considering the correlation between pheromone and hormone, this study focused on the production and perception of pheromones under the endocrine control and highlighted the pivotal roles of nutrition-related pathways. The novel chemicals and gene pathways discovered by recent works provide new insights into the understanding of social regulation of reproductive division of labor in insects.

12.
Org Lett ; 22(20): 7952-7957, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32991188

RESUMO

Difluoroisoxazolacetophenone (DFIO) is developed as a new difluoroalkylation reagent that can be easily prepared from inexpensive starting materials. In situ remote C-C bond cleavage of DFIO affords γ,γ-difluoroisoxazole nitronate that undergoes base-catalyzed vinylogous nitroaldol additions to isatins, benzothiophene-2,3-dione, unsaturated-α-ketoesters, and cyclic 1,2-diketones. This organocatalytic debenzoate vinylogous nitroaldol reaction provides a new and mild approach for the preparation of various difluoroisoxazole-substituted 3-hydroxy-2-oxindoles.

13.
Life Sci ; 261: 118316, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32835698

RESUMO

AIMS: Deubiquitinase ubiquitin-specific protease 33 (USP33) is abnormally expressed in various tumors and participates in tumor progression. However, the expression and biological role of USP33 in hepatocellular carcinoma (HCC) are still unclear. MAIN METHODS: We performed immunohistochemistry, western blotting, and qRT-PCR analysis to determine the expression of USP33 in HCC. We then analyzed the effects of USP33 expression on the prognosis of HCC. The roles of USP33 in regulating HCC cell migration and invasion were further explored in vitro. Animal studies were performed to investigate the effects of USP33 on tumor metastasis. RNA sequencing and luciferase reporter and immunofluorescence assays were used to identify the activation of the specificity protein 1 (SP1)/c-Met axis. KEY FINDINGS: Here, for the first time, we reported an abnormal increase in the expression of USP33 in HCC tissues and that USP33 may act as a prognostic biomarker for HCC patients. We found that USP33 knockdown inhibited the invasion and metastasis in HCC cells both in vitro and in vivo, which was partly dependent on c-Met. Further investigations revealed that USP33 regulated c-Met expression by enhancing the protein stability of the transcription factor SP1 in HCC cells. Mechanistically, USP33 directly bound SP1 and decreased its ubiquitination, thereby upregulating c-Met expression. SIGNIFICANCE: Our results reveal that USP33 acts as the deubiquitinating enzyme of SP1 and contributes to HCC invasion and metastasis through activation of the SP1/c-Met axis. These data indicate a previously unknown function of USP33, which may provide potential targets for the treatment of HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-met/genética , Ubiquitina Tiolesterase/genética , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Prognóstico , Fator de Transcrição Sp1/metabolismo , Regulação para Cima
14.
Cell Biol Int ; 44(10): 2140-2152, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32678496

RESUMO

The pyroptosis is a causative agent of rheumatoid arthritis, a systemic autoimmune disease merged with degenerative articular cartilage. Nevertheless, the precise mechanism of extracellular acidosis on chondrocyte pyroptosis is largely unclear. Acid-sensing ion channels (ASICs) belong to an extracellular H+ -activated cation channel family. Accumulating evidence has highlighted activation of ASICs induced by extracellular acidosis upregulate calpain and calcineurin expression in arthritis. In the present study, to investigate the expression and the role of acid-sensing ion channel 1a (ASIC1a), calpain, calcineurin, and NLRP3 inflammasome proteins in regulating acid-induced articular chondrocyte pyroptosis, primary rat articular chondrocytes were subjected to different pH, different time, and different treatments with or without ASIC1a, calpain-2, and calcineurin, respectively. Initially, the research results showed that extracellular acidosis-induced the protein expression of ASIC1a in a pH- and time-dependent manner, and the messenger RNA and protein expressions of calpain, calcineurin, NLRP3, apoptosis-associated speck-like protein, and caspase-1 were significantly increased in a time-dependent manner. Furthermore, the inhibition of ASIC1a, calpain-2, or calcineurin, respectively, could decrease the cell death accompanied with the decreased interleukin-1ß level, and the decreased expression of ASIC1a, calpain-2, calcineurin, and NLRP3 inflammasome proteins. Taken together, these results indicated the activation of ASIC1a induced by extracellular acidosis could trigger pyroptosis of rat articular chondrocytes, the mechanism of which might partly be involved with the activation of calpain-2/calcineurin pathway.

15.
Hepatology ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32491208

RESUMO

BACKGROUND AND AIMS: Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality. APPROACH AND RESULTS: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79. CONCLUSIONS: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

16.
Exp Cell Res ; 394(2): 112152, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32574605

RESUMO

Protein arginine methyltransferases (PRMTs) have been implicated in the development of various cancers. PRMT2, a member of the type I PRMT family, is overexpressed in multiple tumors. However, the expression and role of PRMT2 in hepatocellular carcinoma (HCC) have not been studied. Here, we discovered that PRMT2 expression is elevated in HCC tissues compared to the corresponding non-tumor tissues, and PRMT2 overexpression is an independent predictor of poor prognosis in HCC patients. Depletion of PRMT2 in HCC cell lines inhibited their cell growth and induced apoptosis. Mechanistic investigations showed that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a). H3R8me2a enrichment at the Bcl2 promoter increases its accessibility to STAT3, promoting Bcl2 gene expression. In addition, our results confirmed that the catalytically inactive mutant of PRMT2 or the type I PRMT inhibitor MS023 impaired the pro-tumorigenic functions of PRMT2 in HCC cells. Overall, our findings showed that PRMT2 functions as an oncogenic gene in HCC, revealing its potential as a novel therapeutic target in HCC.

17.
Vasa ; : 1-6, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32552609

RESUMO

Iliac vein compression syndrome, also known as May-Thurner Syndrome, is a type of vein reflux disorders which is often ignored due to lack of efficient diagnostic methods. The traditional gold standard of diagnosis is venography, but this has been challenged and largely replaced by intravascular ultrasound (IVUS). Here we report a case that a patient suffered with iodine anaphylaxis was successfully performed iliac vein stenting guided by using IVUS alone. This case provides the evidence that IVUS can offer necessary information for physicians in the diagnosis and treatment of iliac vein compression. We also find that balloon dilatation notch cannot precisely reflect the whole lesion, indicating it may be unreliable for diagnosis. Differ from the commonly accepted opinion, we find that comparing to IVUS, the notch of balloon dilatation cannot completely reflect the extent of lesion narrowness. Thus, we think the notch should not be used as a reference for seriousness of the lesion, and the diagnosis of stenosis cannot be ruled out even if there is no presence of notch.

18.
Heliyon ; 6(6): e04097, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32529075

RESUMO

Nutritional and microbiological psychiatry, especially the contribution of the gut microbiota to depression, has become a promising research field over the past several decades. An imbalance in the "microbiota-gut-brain axis", which reflects the constant bidirectional communication between the central nervous system and the gastrointestinal tract, has been used as a hypothesis to interpret the pathogenesis of depression. Alterations in gut microbiota composition could increase the permeability of the gut barrier, activate systemic inflammation and immune responses, regulate the release and efficacy of monoamine neurotransmitters, alter the activity and function of the hypothalamic-pituitary-adrenal (HPA) axis, and modify the abundance of brain-derived neurotrophic factor (BDNF), eventually leading to depression. In this article, we review changes in gut microbiota in depressive states, the association between these changes and depression-like behavior, the potential mechanism linking gut microbiota disruptions and depression, and preliminary attempts at using gut microbiota intervention for the treatment of depression. In summary, although the link between gut microbiota and depression and the potential mechanism have been discussed, a more detailed mechanistic understanding is needed to fully realize the importance of the microbiota-gut-brain axis in depression. Future efforts should aim to determine the potential causative mechanisms, which will require further animal and clinical research as well as the development of analytical approaches.

20.
Liver Int ; 40(7): 1725-1735, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412164

RESUMO

BACKGROUND: Women on the liver transplant waitlist are at greater risk of hospitalization compared with men, but whether this impacts length of stay (LOS) post-transplant is unknown. We aimed to evaluate gender disparities in post-transplant LOS, an important surrogate of health resource utilization post-transplant. METHODS: Using the UNOS/OPTN registry, we analysed all non-Status 1 adult deceased donor liver transplant recipients without exception points from 2008 to 2017. Poisson regression associated female gender with post-transplant LOS. RESULTS: Of 27 294 transplant recipients, 36% were women. Women were more likely to be hospitalized pretransplant than men (44% vs 39%, P < .01). Post-transplant, women were more likely to have prolonged (≥20d) LOS (25% vs 22%, P < .01). In univariable analysis, female gender was associated with longer post-transplant LOS (IRR 1.09, 95%CI 1.06-1.12, P < .01). Prolonged pretransplant admission was also associated with post-transplant LOS (IRR 1.83, 95%CI 1.77-1.89, P < .01). In multivariable analysis, female gender remained independently associated with post-transplant LOS (aIRR 1.05, 95%CI 1.02-1.08, P < .01), after adjustment for age, UNOS region, insurance type, MELDNa, cirrhosis complications, and donor risk index. Pretransplant hospitalization mediated this relationship, explaining 14.1% (95%CI 9.7%-25.4%) of the total effect. CONCLUSIONS: Women who undergo deceased donor liver transplant have increased healthcare utilization in the peritransplant period compared with men. Reducing gender disparities in liver transplantation, including the disproportionate burden of healthcare utilization by women pre- and post-transplant, will require interventions targeted at preventing hospitalization among women on the transplant waitlist and developing tools aimed at better characterizing the severity of end-stage liver disease in women.

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