Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.292
Filtrar
1.
Brain Imaging Behav ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155171

RESUMO

Although numerous studies have revealed the structural and functional alterations in major depressive disorder (MDD) using unimodal diffusion magnetic resonance imaging (MRI) or functional MRI, however, the potential associations between changed microstructure and corresponding functional activities in the MDD has been largely uninvestigated. Herein, 27 medication-free MDD patients and 54 gender-, age-, and educational level-matched healthy controls (HC) were used to investigate the concurrent alterations of white matter microstructure and functional activities using tract-based spatial statistics (TBSS) analyses, fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC). The TBSS analyses revealed significantly decreased fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF I) in the MDD patients compared to HC. Correlation analyses showed that decreased FA in the SLF I was significantly correlated with fALFF in left pre/postcentral gyrus and binary, weighted DC in right posterior cerebellum. Moreover, the fALFF in left pre/postcentral gyrus significantly reduced in MDD patients while binary and weighted DC in right posterior cerebellum significantly increased in MDD patients. Our results revealed concurrent structural and functional changes in MDD patients suggesting that the underlying structural disruptions are an important indicator of functional abnormalities.

3.
Environ Res ; : 110467, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33197421

RESUMO

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33170048

RESUMO

Mitochondrial DNA cytochrome b and d-loop sequences (1,984 bp) from 92 specimens of the freshwater goby Rhinogobius delicatus from seven drainages in East Taiwan were identified as two major lineages exhibiting a southern or northern distribution. The existence of low genetic diversity, a pattern of population decline and high population differentiation (F ST=0.711) support the need for the development of management strategies for the conservation of localized populations. The results of a statistical dispersal-vicariance analysis suggested that the ancestral populations of R. delicatus were widely distributed in East Taiwan. Compared with the phylogeographic patterns of the other endemic eastern Taiwan freshwater fishes, Onychostoma alticorpus, Aphyocypris kikuckii and Hemimyzon taitungensis, our study suggests that the freshwater fishes colonized East Taiwan through northeastern and southwestern Taiwan, although the ancestral populations colonized the island before it reached its present shape.

5.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4692-4698, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164434

RESUMO

The aim of this paper was to investigate the effect of total polysaccharide from Balanophora henryi(TBP) on alcoholic liver disease(ALD) and explore the possible mechanism. C57 BL/6 N mice were randomly divided into 4 groups: pair-feeding group, alcohol-feeding model group, model+TBP group and TBP drug control group. The Gao-binge method was used to prepare the chronic ALD model, and at the same time, 400 mg·kg~(-1) TBP was given for interventional therapy. After feeding for 6 weeks, the serum, liver and colon tissues were collected for detection. As compared with the pair-feeding group, the model group mice showed obvious fatty degeneration and a large number of infiltration of inflammatory cells in the liver, with increased serum ALT and AST levels. After TBP intervention, histopathological changes in liver tissues were significantly improved, with decreased lipid deposition, closer arrangement of hepatocytes, lower expression level of inflammatory factors, and reduced activity of serum ALT and AST, indicating that TBP had a significant improvement effect on ALD. The observation of colonic tissues in mice showed that TBP effectively maintained the integrity of intestinal tissue structure of mice with ALD, enhanced the expression of tight junction protein occludin and reduced miR-122 a expression level. More importantly, TBP significantly reduced serum lipopolysaccharide(LPS) level in model mice. These results indicated that TBP may improve ALD by maintaining and enhancing intestinal barrier function. In vitro experiments showed that TBP significantly inhibited the expression level of miR-122 a in Caco-2 cells exposed to ethanol. Overexpression of miR-122 a in Caco-2 cells induced the inhibition of occludin protein production, and the addition of TBP significantly interfered with the effect. These results suggested that TBP could improve ALD by maintaining the stability of intestinal barrier function and reducing LPS content into the liver, and the mechanism may be partially related to inhibiting miR-122 a expression.


Assuntos
Hepatopatias Alcoólicas , MicroRNAs , Animais , Células CACO-2 , Humanos , Fígado , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Ocludina/genética
6.
Mol Cells ; 43(11): 935-944, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33168788

RESUMO

Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

7.
Exp Biol Med (Maywood) ; : 1535370220970130, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231514

RESUMO

Hepatocellular carcinoma is a malignance that remains difficult to cure. Immunotherapy has shown its potential application in a variety of refractory malignancies. Due to the complexity of immune microenvironment of hepatocellular carcinoma, the efficacy of immunotherapy for hepatocellular carcinoma is not as effective as expected. Expression data of hepatocellular carcinoma from the TCGA and ICGC databases were used for classification and verification of hepatocellular carcinoma subtypes. The immune-related functions and pathways were identified via gene set enrichment analysis, while the sections denoting the subsets of the immune cells were estimated using the CIBERSORT algorithm. Immunity low (Immunity_L), immunity medium (Immunity_M), and immunity high (Immunity_H) were specified as the three immune-related subtypes of hepatocellular carcinoma. The quantity of stromal and immune cells was the most substantial in Immunity_H, compared to the other subtypes. Interestingly, the proportion of M0 macrophages decreased from Immunity_L to Immunity_H, while the proportion of CD8 T cells increased. Furthermore, the HLA genes expression levels, as well as those of six immune checkpoint genes were substantially lower in Immunity_L than in Immunity_H. Functional analysis was performed for 1512 differentially expressed genes between Immunity_L and Immunity_H. Finally, the PPI network was constructed with 118 nodes. The highest connectivity degree nodes were B2M, HLA-DRA, and HLA-DRB1. The above results were verified in ICGC-JP and ICGC-FR databases with a consistent trend. In this study, we divided hepatocellular carcinoma into three subtypes and explored the immune-related characteristics of these subtypes. These results may provide new insights for immunotherapy of hepatocellular carcinoma.

8.
Sci Rep ; 10(1): 18973, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149113

RESUMO

Inhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study. Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included. Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods. To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied. Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1-2.9). The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52-0.89). When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55-0.88) in the highest quartile ICS dose use. The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers. Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD. Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD.

10.
Cancer Lett ; 497: 212-220, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33132120

RESUMO

Stress conditions induced by routine treatments might affect cancer-associated fibroblasts in lung adenocarcinoma. The present study tried to explore transcriptome changes in lung fibroblasts under chemotherapeutics, irradiation, and hypoxia, which were induced by chemotherapy, radiotherapy, and anti-angiogenesis therapy, respectively. We established three in vitro models to mimic the stress conditions for lung fibroblasts. Interestingly, one of the secretory molecules, tumor necrosis factor superfamily member 4 (TNFSF4, also known as OX40L), was significantly up-regulated in lung fibroblasts under stress environments. Lung adenocarcinoma patients received chemotherapy and radiotherapy had a higher expression level of TNFSF4 in serum and tumor tissues. There was a negative correlation between the increase of serum TNFSF4 levels and the shrink of the tumor after chemotherapy. TNFSF4 could promote cisplatin resistance and inhibit the apoptosis of lung adenocarcinoma cells. Furthermore, TNFSF4 could significantly increase the activity of NF-κB/BCL-XL pathway in lung adenocarcinoma cells, which could be counteracted by knocking down the expression of TNFRSF4 (receptor of TNFSF4). In conclusion, TNFSF4, secreted by cancer-associated fibroblasts under stress conditions, could facilitate chemoresistance of lung adenocarcinoma through inhibiting apoptosis of tumor cells.

11.
Int J Surg Case Rep ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33169098

RESUMO

Introduction: This case is shared to reiterate and confirm the principles of ensuring the safety of the surgical team caring for COVID-19-confirmed patients, thus, preventing the spread of infection within the hospital. Case presentation: A 54-year-old male, COVID-19-confirmed patient complaining of abdominal pain since two days prior was transferred to our hospital. Perforated appendicitis with a periappendiceal abscess was diagnosed by computed tomography. Laparoscopic appendectomy was performed in a negative-pressure operating room. The surgical team wore enhanced personal protective equipment. Electrocautery was not used during surgery and no other special instruments were applied to reduce aerosol generation. No special instruments or filters were used for the removal of intra-abdominal gas. The operation was completed successfully and no immediate surgical complications occurred. The patient advanced to a normal diet on the 4th postoperative day. The patient was treated with antibiotics for bacteremia and antiviral therapy for underlying pneumonia in the setting of COVID-19 with most symptoms dissipating by the 7th postoperative day. The patient was discharged on the 30th postoperative day without any complications. Discussion: A well-designed manual, a well-trained surgical team, and a negative-pressure operating room are essential for safe laparoscopic appendectomies in COVID-19 patients. Conclusion: When surgery is performed in a negative-pressure operating room by a well-trained surgical team, a laparoscopic appendectomy can be successfully performed under the principles of obtaining optimum clinical outcomes while faithfully ensuring the safety of healthcare providers and the hospital environment.

12.
Zootaxa ; 4860(1): zootaxa.4860.1.6, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33056175

RESUMO

A new species of the xenodermatid snake genus Achalinus Peters, 1869 is described from Yunnan Province, Southwest China, based on a single male specimen. The new species is assigned to the genus Achalinus on the basis of absence of preocular and postocular, subcaudals arranged in single row, and results of phylogenetic analyses of mitochondrial DNA CO1 sequence data. Achalinus pingbianensis sp. nov. differs from its congeners by the combination of following morphological characters: absence of a loreal, internasals subequal to that between prefrontals and dorsal scales strongly keeled, 23 rows throughout. Currently, 13 species are in the genus Achalinus, further taxonomical and phylogenetic studies based on more extensive samples and more markers will help understand the cryptic diversity and clarify their interspecific relationships.


Assuntos
Serpentes , Distribuição Animal , Estruturas Animais , Animais , China , Masculino , Filogenia
13.
Medicine (Baltimore) ; 99(43): e22924, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120846

RESUMO

RATIONALE: Polymyxin B has been used to treat extensively drug-resistant gram-negative bacteria and shown a better antibacterial effect in the clinic at present. Meanwhile, polymyxin B is associated with several adverse effects. However, there is a lack of awareness that polymyxin B can cause rhabdomyolysis. In this study, we firstly report a case of polymyxin B-induced rhabdomyolysis during antiinfection therapy. PATIENT CONCERNS: A 70-year-old woman suffering from rheumatic heart disease underwent aortic and mitral valve replacement at our institute. Subsequently, she developed bacteremia and pneumonia caused by extensively drug resistance-acinetobacter baumannii. Polymyxin B was administered for 5 days. During treatment, the patient complained of muscle pain and limb weakness, and her serum creatine phosphokinase and myoglobin levels rose. DIAGNOSIS: The clinical symptoms and laboratory examination confirmed rhabdomyolysis, and polymyxin B-induced rhabdomyolysis was considered. INTERVENTION: We ceased polymyxin B treatment and monitored the patient daily. OUTCOMES: Serum creatine phosphokinase levels returned to normal, myoglobin levels decreased, and muscle pain was significantly alleviated after cessation of polymyxin B. We identified this as a case of polymyxin B-induced rhabdomyolysis. LESSONS: Here, we report the first reported case of rhabdomyolysis induced by polymyxin B administration. The awareness of rare adverse reaction helps ensure the clinical safety of polymyxin B treatment.


Assuntos
Antibacterianos/efeitos adversos , Polimixina B/efeitos adversos , Rabdomiólise/induzido quimicamente , Acinetobacter baumannii/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Conscientização , Bacteriemia/tratamento farmacológico , Creatina Quinase/sangue , Feminino , Humanos , Debilidade Muscular/etiologia , Mialgia/etiologia , Mioglobina/sangue , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Rabdomiólise/diagnóstico , Suspensão de Tratamento
14.
J Clin Invest ; 130(11): 5782-5799, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33016927

RESUMO

Glioblastoma multiforme (GBM) heterogeneity causes a greater number of deaths than any other brain tumor, despite the availability of alkylating chemotherapy. GBM stem-like cells (GSCs) contribute to GBM complexity and chemoresistance, but it remains challenging to identify and target GSCs or factors that control their activity. Here, we identified a specific GSC subset and show that activity of these cells is positively regulated by stabilization of methyl CpG binding domain 3 (MBD3) protein. MBD3 binds to CK1A and to BTRCP E3 ubiquitin ligase, triggering MBD3 degradation, suggesting that modulating this circuit could antagonize GBM recurrence. Accordingly, xenograft mice treated with the CK1A activator pyrvinium pamoate (Pyr-Pam) showed enhanced MBD3 degradation in cells expressing high levels of O6-methylguanine-DNA methyltransferase (MGMT) and in GSCs, overcoming temozolomide chemoresistance. Pyr-Pam blocked recruitment of MBD3 and the repressive nucleosome remodeling and deacetylase (NuRD) complex to neurogenesis-associated gene loci and increased acetyl-histone H3 activity and GSC differentiation. We conclude that CK1A/BTRCP/MBD3/NuRD signaling modulates GSC activation and malignancy, and that targeting this signaling could suppress GSC proliferation and GBM recurrence.

15.
Plant Cell Environ ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043459

RESUMO

Soil salinization is a major threat to global food security and the biodiversity of natural ecosystems. To adapt to salt stress, plants rely on ROS-mediated signalling networks that operate upstream of a broad array of physiological and genetic processes. A key player in ROS signalling is NADPH oxidase, a plasma-membrane-bound enzyme encoded by RBOH genes. In this study, we have conducted a comprehensive bioinformatic analysis of over 50 halophytic and glycophytic species to link the difference in the kinetics of ROS signalling between contrasting species with the abundance and/or structure of NADPH oxidases. The RBOH proteins were predicted in all the tested plant lineages except some algae species from the Rhodophyta, Chlorophyta and Streptophyta. Within the glycophytic group, the number of RBOH copies correlated negatively with salinity stress tolerance, suggesting that a reduction in the number of RBOH isoforms may be potentially related to the evolution of plant salinity tolerance. While halophytes did not develop unique protein families during evolution, they evolved additional phosphorylation target sites at the N-termini of NADPH oxidases, potentially modulating enzyme activity and allowing more control over their function, resulting in more efficient ROS signalling and adaptation to saline conditions.

16.
Biochem Genet ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098307

RESUMO

Retinoblastoma (Rb) is the most common pediatric malignant tumor of the eyes. Previous studies demonstrated that miR-491-3p is downregulated in various cancers. However, its function in Rb remains unknown. A total of 15 pairs of primary Rb tissues and adjacent noncancerous tissues were collected. Quantitative real-time PCR (qRT-PCR) was used to investigate the expression profiles of miR-491-3p. qRT-PCR, western blotting and in situ immunocytochemistry were performed to investigate the expression profiles of epithelial-mesenchymal transition-related proteins (E-cadherin, Vimentin and N-cadherin) in Rb tissues and Rb cell lines as well as cell morphology. Cell proliferation was estimated by MTS and colony formation assays. Apoptosis was determined by FACS, cell migration and invasion were analyzed using transwell chambers. MiR-491-3p's target genes were predicted using target gene prediction databases. The interplay between miR-491-3p and SNN was evaluated through dual luciferase reporter gene assay. MiR-491-3p was significantly downregulated in mixed collection of 15 pairs of Rb tissues and Rb cell lines. Overexpression of miR-491-3p enhanced apoptosis, and significantly suppressed proliferation, migration and invasion of Rb cells. In contrast, the present of miR-491-3p inhibitor showed reversed results which apoptosis decreased, while cell proliferation of ARPE-19 cells increased. In addition, miR-491-3p increased the expression of E-cadherin, and dramatically decreased the expression of Vimentin and N-cadherin in Rb tissues and Rb cell lines, noticeable changes in morphology, too, as cells became less cohesive and more adhering. We found out that SNN was the pairing target of miR-491-3p and result showed that miR-491-3p and SNN interacted with each other. We also found out that the effects of miR-491-3p were in Rb cells were almost entirely canceled out at the overexpression of SNN. Our findings collectively suggest that miR-491-3p is an important tumor suppressor in Rb, which inhibits tumor growth and metastasis in Rb. These implicate it may be explored as a new therapeutic target in Rb.

18.
Disabil Rehabil ; : 1-8, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103489

RESUMO

PURPOSE: The Motor-Free Visual Perception Test-4 (MVPT-4) is a multidimensional measure of visual perception with five subscales (visual discrimination, figure-ground, visual memory, spatial relationships, and visual closure). The purpose of this study was to examine practice effect and test-retest reliability of the MVPT-4 over four serial assessments in patients with stroke. METHODS: We recruited outpatients with stroke with age above 20 years, able to follow instructions, and able to sign informed consent. We excluded patients who had visual neglect and visual deficits (e.g., diplopia, cataract, and glaucoma). Sixty patients completed the MVPT-4 four times, one week apart. Cumulative and plateau phases of the practice effect were evaluated across four assessments. Test-retest reliability was examined using the intraclass correlation coefficient (ICC). RESULTS: The MVPT-4 scale and five subscales showed cumulative phases. Only the spatial relationships subscale may have reached a plateau phase at the second assessment. The ICC values of the MVPT-4 scale and five subscales were 0.48-0.87. The minimum and maximum values of the 90% confidence interval (CI) of reliable change index modified for practice (RCIp) were: MVPT-4 scale [-5.0, 7.7]; visual discrimination [-1.7, 2.1]; figure-ground [-2.0, 2.6]; visual memory [-2.6, 3.2]; spatial relationships [-2.3, 3.0]; and visual closure [-2.5, 2.8]. CONCLUSIONS: The MVPT-4 scale and five subscales appeared increasing trends of practice effects and moderate to excellent test-retest reliability in patients with stroke. The minimum and maximum values of the 90% CI RCIp for the spatial relationships subscale which may have reached a plateau phase that can help clinicians and researchers to ascertain whether the real score change is occurred for an individual patient. Implications for rehabilitation Three multilevel regression models were conducted to evaluate the plateau phase of the practice effect over four assessments. The patterns of practice effects and evidences of test-retest reliability of the MVPT-4 scale and five subscales over four serial assessments can be used to follow the progress of patients with stroke. The minimum and maximum values of the 90% CI RCIp of the MVPT-4 can assist clinicians and researchers to explain score changes for an individual patient with stroke.

19.
Front Endocrinol (Lausanne) ; 11: 573891, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071980

RESUMO

Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions. Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment. Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results. Conclusions: The changes in specific taxa and ß-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.

20.
Dis Markers ; 2020: 8539804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082884

RESUMO

Aim: The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments. Methods: The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments. Results: First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM (r = 0.615, P < 0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC = 0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), P = 0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), P = 0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), P = 0.048), reflecting continued worsening of liver fibrosis. Conclusion: CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA