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1.
J Ethnopharmacol ; 246: 112240, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31526861

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a famous Chinese traditional medicine compound that has been used to treat renal function diseases for more than 300 years. It is recorded in Jing Yue Quanshu, which was written by a famous medical scientist named Jiebing Zhang in the Ming Dynasty. AIM OF THE STUDY: Reproductive dysfunction is one of the most serious complications of chronic kidney disease (CKD). The aim of this study was to observe the effect of You-Gui-Yin (YGY) on reproductive dysfunction of male rats with adenine-induced CKD and to determine if any effects occurred via regulation of the HIF1α-STAT5 pathway. MATERIALS AND METHODS: UPLC-Q-TOF-MS was used to detect the main medicinal components and conduct quality control of YGY. A total of 60 rats were randomly divided into 2 groups: the NC group (10 rats) and the CKD model group (50 rats). The CKD model rats was established by administration of adenine 150 mg kg-1 orally for 14 days. After that, the CKD rats were randomly divided into 5 groups: the CKD group, YGY (10 g kg-1 group, 20 g kg-1 group, 40 g kg-1 group) and the GUI-LU-ER-XIAN-JIAO (GL) 10 g kg-1 group with 10 rats in each group. From the 15th day to the 45th day rats were given 150 mg kg-1 adenine orally every other day to maintain the model (except in the NC group). The YGY groups and the GL group were orally administered the relevant drug once per day for 30 days. The NC group and the CKD group were orally administered an equal volume of normal saline for 30 days. On the 45th day, the rats' sexual behavior index was tested. On the 46th day, the rats were sacrificed. Biochemical indexes, histopathological changes of the kidneys and testes, sperm morphology, sperm abnormality rate, and key proteins in the HIF1α-STAT5 pathway in the kidney and testis were detected. RESULTS: Thirteen components in the YGY extract were identified by UPLC-Q-TOF-MS for quality control of the YGY extract. The results of the biochemical and physiological tests validated the success of inducing CKD accompanied by reproductive dysfunction in rats. YGY significantly retarded the CKD progression and improved the hormone levels of male CKD rats. Sexual behavior tests showed YGY can significantly improve CKD rats' sexual function. In addition, the pathological changes of the kidney and testis, sperm abnormality rate and sperm morphological abnormalities of the CKD rats were reduced by YGY. Furthermore, decreased expression of HIF1α and EPO, and increased expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) were observed in the kidney and the testis of the CKD rats. The YGY extract dramatically increased the expression of HIF1α and EPO, and decreased the expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) to regulate key proteins in the HIF1α-STAT5 pathway of the kidney and testis. CONCLUSIONS: YGY has obvious reversal effects on the abnormal symptoms of adenine-induced CKD and the abnormal symptoms of rats with hypothyroidism and male reproductive hypotension. Its mechanism is related to its ability to regulate the HIF1α-STAT5 pathway.

2.
Food Chem ; 306: 125593, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610327

RESUMO

The heat-induced aggregation of edible proteins has been regarded as one of the critical challenges for their application in protein-enriched beverages. Therefore, the formulation of thermal stable proteins to improve the stability of these beverages upon heating is highly desired. In this study, soy proteins (SPs) with enhanced heat stability were obtained by low-concentration-preheating (LCPH). Results from reheating of the above samples showed that pretreatment of SPs at low concentrations (≤1.0%, w/v) increased their resistance against aggregation. Additionally, when the suspensions of the particles were reheated at 10% (w/v) protein concentration, no gelation was found for samples prepared by LCPH, indicating collapsed protein-protein interactions, whereas gelled suspensions were obtained for native SPs and samples prepared by preheating at higher protein concentrations (≥2.0%, w/v). Furthermore, suspensions of particles prepared at lower protein concentration showed lower viscosities and higher flow behavior index values before and after reheat treatment. These findings highlighted that LCPH would provide fundamental information on the application of SPs in high protein beverages.

3.
Clin Chem ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672855

RESUMO

BACKGROUND: Molecular profiling has become essential for tumor risk stratification and treatment selection. However, cancer genome complexity and technical artifacts make identification of real variants a challenge. Currently, clinical laboratories rely on manual screening, which is costly, subjective, and not scalable. We present a machine learning-based method to distinguish artifacts from bona fide single-nucleotide variants (SNVs) detected by next-generation sequencing from nonformalin-fixed paraffin-embedded tumor specimens. METHODS: A cohort of 11278 SNVs identified through clinical sequencing of tumor specimens was collected and divided into training, validation, and test sets. Each SNV was manually inspected and labeled as either real or artifact as part of clinical laboratory workflow. A 3-class (real, artifact, and uncertain) model was developed on the training set, fine-tuned with the validation set, and then evaluated on the test set. Prediction intervals reflecting the certainty of the classifications were derived during the process to label "uncertain" variants. RESULTS: The optimized classifier demonstrated 100% specificity and 97% sensitivity over 5587 SNVs of the test set. Overall, 1252 of 1341 true-positive variants were identified as real, 4143 of 4246 false-positive calls were deemed artifacts, whereas only 192 (3.4%) SNVs were labeled as "uncertain," with zero misclassification between the true positives and artifacts in the test set. CONCLUSIONS: We presented a computational classifier to identify variant artifacts detected from tumor sequencing. Overall, 96.6% of the SNVs received definitive labels and thus were exempt from manual review. This framework could improve quality and efficiency of the variant review process in clinical laboratories.

4.
Brain Behav Immun ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669519

RESUMO

The vicious cycle between the chronicactivationofmicroglia and dopamine neurons degeneration is linked with the progression of Parkinson's disease (PD). Targeting microglialactivationhas proven to be a viable option to develop a disease-modified therapy for PD. Galectin-1, which has been reported to have an anti-neuroinflammation effect was used in the present study to evaluate its therapeutic effects on microglia activation and neuronal degeneration in Parkinson's disease model. It was found that galectin-1 attenuated the inflammatory insult and the apoptosis of SK-N-SH human neuroblastoma cells from conditioned medium of activated microglia induced by Lipopolysaccharides (LPS). Nonetheless, galectin-1 administration (0.5 mg/kg) inhibited the microglia activation, improved the motor deficits in PD mice model induced by MPTP (25 mg/kg weight of mouse, i.p.) and prevented the degeneration of dopaminergic neurons in the substantia nigra. Administration of galectin-1 resulted in p38 and ERK1/2 dephosphorylation followed by IκB/NFκB signaling pathway inhibition. Galectin-1 significantly decreased the secretion of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The protective effects and modulation of the MAPK/IκB/NFκB signaling pathway were abolished with ß-D-galactose which blocked the carbohydrate-recognition domain of galectin-1. The present study demonstrated that galectin-1 inhibited microglia activation and ameliorated neurodegenerative process in PD model by modulating MAPK/IκB/NFκB axis through its Carbohydrate-recognition domain.

5.
Hepatology ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587343

RESUMO

We read with great interest the article by Choi et al.(1) reporting the impacts of concomitant non-alcoholic steatohepatitis (NASH) on the clinical outcomes and all-cause mortality in chronic hepatitis B (CHB) patients. Although the number of patients and follow-up duration are quite impressive, several points require further clarification.

6.
ACS Nano ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585038

RESUMO

Elevated hydrogen peroxide (H2O2) in biological tissues is generally recognized to be relevant to the carcinogenesis process that regulates the proliferative activity of cancer cells and the transformation of malignant features. Inspired by this observation, it can be hypothesized that imaging H2O2 in the tumor microenvironment (TME) could help diagnose tumor types and malignancy, and even guide precise therapy. Thus, in this study, a noninvasive photomedicine strategy is demonstrated that leverages the different levels of H2O2 in the TME, and two representative skin cancers, malignant melanoma (MM, clinically higher incidence of metastasis and recurrence) and cutaneous squamous cell carcinoma (cSCC, relatively less dangerous), are differentially diagnosed. The working probe used here is one we previously developed, namely, intelligent H2O2 responsive ABTS-loaded HRP@Gd nanoprobes (iHRANPs). In this study, iHRANPs have advantages over ratiometric imaging due to their bimodal imaging elements, in which the inherent magnetic resonance imaging (MR) mode can be used as the internal imaging reference and the H2O2 responsive photoacoustic (PA) imaging modality can be used for differential diagnosis. Results showed that after intravenous injection of iHRANPs, the tumor signals on both MM and cSCC are obviously enhanced without significant difference under the MR modality. However, under the PA modality, MM and cSCC can be easily distinguished with obvious variations in signal enhancement. Particularly, guided by PA imaging, photothermal therapy (PTT) can be precisely applied on MM, and a strong antitumor effect was achieved owing to the excessive H2O2 in the TME of MM. Furthermore, exogenous H2O2 was injected into cSCC to remedy H2O2 deficiency in the TME of cSCC, and an evident therapeutic efficacy on cSCC can also be realized. This study demonstrated that MM can be differentially diagnosed from cSCC by noninvasive imaging of H2O2 in the TME with iHRANPs; meanwhile, it further enabled imaging-guided precision PTT ablation, even for those unsatisfactory tumor types (cSCC) through exogenously delivering H2O2.

7.
Chin Med Sci J ; 34(3): 199-204, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601303

RESUMO

Objective Psoriasis is an immune-mediated inflammatory disease. Despite advances in the study of its pathogenesis, the exact development mechanism of psoriasis remains to be fully elucidated. Hyperproliferative epidermis plays a crucial role in psoriasis. This study aimed to investigate the effects of interleukin-36ß (IL-36ß) on keratinocyte dysfunction in vitro. Methods Human keratinocyte cell lines, HaCaT cells, were treated with 0 (control), 50 or 100 ng/ml IL-36ß respectively for 24 h. Cell viability was determined with a cell counting kit-8 assay. Flow cytometry was used to assess the effects of IL-36ß on apoptosis and cell cycle distribution. Expressions of the differentiation markers, such as keratin 10 and involucrin, were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Expressions of the inflammatory cytokines, IL-1ß and IL-6 were tested by ELISA. Results CCK8 assay showed the survival rate had no significant difference between the control and treated group (P > 0.05). Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36ß-treated groups compared with the control group (P < 0.05). RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36ß-treated groups compared with the negative control (P < 0.01). ELISA showed 100 ng/ml IL-36ß enhanced levels of IL-1ß and IL-6 in culture supernatants of HaCaT cells compared with the negative control (P < 0.05). Conclusion Taken together, these findings suggest that IL-36ß could induce cell cycle arrest at S phase, inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.

8.
Nat Med ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591597

RESUMO

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.

9.
J Ethnopharmacol ; : 112301, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31622746

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Babaodan (BBD), a famous traditional Chinese medicine used in clinic, has a strong effect on eliminating jaundice, awakening and enlightening the mind. This paper assesses the preventive and therapeutic effect of BBD on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism. METHODS: The establishment of CHE and AHE rat models: hepatic fibrosis and acute liver failure rat model established by injection of carbon tetrachloride (CCl4) were pretreated with BBD and then induced into hepatic encephalopathy by injection of thioacetamide (TAA). Preventive and therapeutic effect of BBD on brain dysfunction, liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway were detected in both liver and brain in vivo. The rat BMDMs were activated by Lipopolysaccharide (LPS) and the role of BBD in regulation of inflammatory factors and NK-κ B pathway were detected in vitro. RESULTS: In CHE rat model: the total distance and activity rate of the rats with the low dose BBD (BL), high dose BBD (BH) and Lactulose (L) groups significantly improved, and the BH group improved most obviously. BBD can effectively reduce ammonia levels. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA) in CHE rats after BBD intervention were significantly lower, and TP and Alb levels were significantly higher. In the liver, BBD not only inhibited the gene expression of tumor necrosis factor alpha (TNF-a), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B, but also inhibited the protein expression of TLR4, MyD88, NK-κ B and TNF-a. In the brain, BBD inhibited the gene expression of iNOS, IL-6, TNF-a, TLR-4, M yD88, and NF-κ B, as well as inhibited the protein expression of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). In the blood, NO and TNF-α were also improved by BBD. In AHE rats model: BBD improved neurological score and blood ammonia and inhibited brain inflammatory gene expression of iNOS, TNF-α and IL-1ß. BBD also improved liver function markers such as ALT, AST, TBiL, TBA, TP, Alb and inhibited inflammatory and apoptotic gene expression of genes such as TNF-α, IL-1ß, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat bone marrow-derived macrophages (BMDM), BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expression of TNF-α, IL-1 ß and IL-6 as well as the phosphorylation of P65. CONCLUSION: BBD could prevent and cure hepatic encephalopathy derived from both chronic and acute liver diseases. Here, we found that except for the direct improvement of blood and brain ammonia level, inflammation is likely an important target of BBD to treat hepatic encephalopathy. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.

10.
Chem Biodivers ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612620

RESUMO

One new p-terphenyl compound gliocladinins C and two disubstituted tetrahydrofuran derivatives chaetominin A and B were isolated from potato endophytic fungus  Chaetomium subaffine . The absolute configurations of these compounds were elucidated by HR-ESI-MS, NMR, the DP4+ probabilities and electronic circular dichroism (ECD) spectra. In addition gliocladinins C and chaetominin A showed cytotoxin activity against two selected human tumor cell lines (Hep-2 and HepG-2).

11.
Scand J Clin Lab Invest ; : 1-12, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663373

RESUMO

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.

12.
Am J Gastroenterol ; 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31634265

RESUMO

INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77). DISCUSSION: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.

13.
FASEB J ; 33(11): 13051-13061, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31589480

RESUMO

Polycystic kidney disease (PKD) is characterized by the expansion of fluid-filled cysts in the kidney, which impair the function of kidney and eventually leads to end-stage renal failure. It has been previously demonstrated that transgenic overexpression of prothymosin α (ProT) induces the development of PKD; however, the underlying mechanisms remain unclear. In this study, we used a mouse PKD model that sustains kidney-specific low-expression of Pkd1 to illustrate that aberrant up-regulation of ProT occurs in cyst-lining epithelial cells, and we further developed an in vitro cystogenesis model to demonstrate that the suppression of ProT is sufficient to reduce cyst formation. Next, we found that the expression of ProT was accompanied with prominent augmentation of protein acetylation in PKD, which results in the activation of downstream signal transducer and activator of transcription (STAT) 3. The pathologic role of STAT3 in PKD has been previously reported. We determined that this molecular mechanism of protein acetylation is involved with the interaction between ProT and STAT3; consequently, it causes the deprivation of histone deacetylase 3 from the indicated protein. Conclusively, these results elucidate the significant role of ProT, including protein acetylation and STAT3 activation in PKD, which represent potential for ameliorating the disease progression of PKD.-Chen, Y.-C., Su, Y.-C., Shieh, G.-S., Su, B.-H., Su, W.-C., Huang, P.-H., Jiang, S.-T., Shiau, A.-L., Wu, C.-L. Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice.

14.
Pediatr Rheumatol Online J ; 17(1): 69, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651352

RESUMO

BACKGROUND/PURPOSE: Endothelium is a key element in the regulation of vascular homeostasis and its alteration can lead to the development of vascular diseases. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with potential extensive vascular lesions, involving skin vessels, renal glomeruli, cardiovascular system, brain, lung alveoli, gastrointestinal tract vessels and more. We aimed to assess endothelial dysregulation related biomarkers in pediatric-onset SLE (pSLE) patient serum and elucidate its correlation with their clinical features, laboratory parameters, and the overall disease activity. METHODS: Disease activities were evaluated by SLE disease activity index (SLEDAI). Patient characteristics were obtained by retrospective chart review. Six biomarkers associated with endothelial dysregulation, including Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie2, Vascular endothelial growth factor (VEGF), thrombomodulin, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) were tested through enzyme-linked immunosorbent assay (ELISA) measurement. RESULTS: This study comprised 118 pSLE patients. Data from 40 age-matched healthy controls were also obtained. The mean diagnostic age was 13 ± 4.12 years-old and 90.7% are females. Serum levels of VEGF, Tie2, thrombomodulin were significantly higher while serum ADAMTS13 was lower in active pSLE patients when compared to those with inactive diseases (all p < 0.05). In organ specific association, serum thrombomodulin level was higher in pSLE patient with renal involvement, and serum ADAMTS13 levels was negatively associated with neurological involvement (p < 0.05). A cutoff of thrombomodulin at 3333.6 pg/ml best correlated renal involvement. (AUC = 0.752, p < 0.01). CONCLUSION: Endothelial dysregulation associating proteins seems to be potent biomarkers for pSLE activity as well as organ involvement in pSLE patients. These biomarkers may be beneficial in understanding of the vascular pathogenesis and disease monitoring.

15.
Curr Opin Biotechnol ; 64: 47-54, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31655339

RESUMO

Quantitative understanding of clostridial metabolism is of longstanding interest due to the importance of Clostridia as model anaerobes, biotechnology workhorses, and contributors to evolutionary history and ecosystem. Current computational methods such as flux balance analysis-based construction of clostridial metabolism in genome scale provide a fundamental framework for metabolic analysis. However, this method alone is inadequate to characterize cellular metabolic activity. Experiment-driven approaches including isotope tracer-based fluxomics in association with genetic and biochemical methods are needed to gain a more comprehensive understanding. Here we focus on typical examples where these integrated approaches have contributed to the identification of new metabolic pathways and quantification of metabolic fluxes in Clostridia. We also highlight the opportunities and challenges of cutting-edge fluxomics approaches such as machine learning modeling, deuterium tracer approach, and high throughput flux phenotyping in exploring clostridial metabolism with respect to inorganic carbon utilization, redox cofactor interconversion, and other key metabolic features.

16.
Clin Pharmacol Ther ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31628864

RESUMO

Hyperuricemia has been associated with chronic kidney disease (CKD) progression. The anti-hyperuricemic febuxostat's potential renoprotective effect has been demonstrated in stage 1-3 CKD. Large-scale studies comparing the renoprotective potential of febuxostat and allopurinol in advanced CKD are lacking. We exclusively selected 6057 eligible pre-dialysis stage 5 CKD patients prescribed either febuxostat or allopurinol using the National Health Insurance Research Database in Taiwan during 2012-2015. 69.57% of allopurinol users and 42.01% febuxostat users required long-term dialysis (p<.0001). The adjusted hazard ratio (HR) of 0.65 (95% confidence interval 0.60-0.70) indicated near 35% lower hazards of long-term dialysis with febuxostat use. The renal benefit of febuxostat was consistent across most patient subgroups and/or using the propensity score-matched cohort. The adjusted HR was 0.66 (95% confidence interval 0.61-0.70) for long-term dialysis or death. In conclusion, lower risk of progression to dialysis was observed in pre-dialysis stage 5 CKD febuxostat users without compromising survival.

17.
BMC Infect Dis ; 19(1): 840, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615434

RESUMO

BACKGROUND: CD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population. METHODS: Three single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis. RESULTS: After adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR = 1.368, 95%CI = 1.070-1.749, P = 0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR = 1.397, 95%CI = 1.078-1.809, P = 0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR = 1.337, 95%CI = 1.069-1.673, P = 0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR = 1.351, 95%CI = 1.060-1.702, P = 0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P > 0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P = 0.029, P = 0.047 and P<0.001, respectively). CONCLUSIONS: In conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations.

18.
Phys Rev E ; 100(3-1): 032133, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31640021

RESUMO

The two-lane driven system is a type of important model to research some transport systems, and also a powerful tool to investigate properties of nonequilibrium state systems. This paper presents a driven bidirectional two-lane model. The dynamic characteristics of the model with periodic boundary are investigated by Monte Carlo simulation, simple mean field, and cluster mean field methods, respectively. By simulations, phase separations are observed in the system with some values of model parameters. When the phase separation does not occur, cluster mean field results are in good agreement with simulation results. According to the cluster mean field analysis and simulations, a conjecture about the condition that the phase separation happens is proposed. Based on the conjecture, the phase boundary distinguishing phase separation state and homogeneous state is determined, and a corresponding phase diagram is drawn. The conjecture is validated through observing directly the spatiotemporal diagram and investigating the coarsening process of the system by simulation, and a possible mechanism causing the phase separation is also discussed. These outcomes maybe contribute to understand deeply transport systems including the congestion and efficiency of the transport, and enrich explorations of nonequilibrium state systems.

19.
Chem Commun (Camb) ; 55(85): 12781-12784, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31589236

RESUMO

A non-precious-metal catalyst, specifically made up of cobalt-embedded nitrogen-doped carbon nanotubes (Co-N-CNTs), was synthesized by subjecting a Prussian blue analogue to annealing decomposition. These Co-N-CNTs were employed as the cathode catalyst of a Li-CO2 battery, and helped this battery deliver a high capacity and outstanding cyclability. Furthermore, we verified the reversibility of this Li-CO2 battery.

20.
Phys Chem Chem Phys ; 21(42): 23533-23540, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31617516

RESUMO

This work demonstrates that the mono(Lewis base)-stabilized three-center-six-electron (3c-6e) or LB → B-R type borylenes may have a ground state singlet (σ2π0 and σ0π2) or triplet (σ1π1) electronic structure, depending on the substitution group, Lewis base, and molecule topology (cyclic or acyclic). The singlet-triplet energy gap of a borylene increases with electron-donating substitution groups and decreases with Lewis bases of strong σ-donating and π-accepting feature (e.g., carbenes and pyridine). The gap can be widely varied (ranging up to about 300 kJ mol-1) and even inversed by the proper combination of substitution groups and Lewis bases. These borylenes may even have singlet-and-triplet coexisting ground state electronic structures, which imply their complex reactivity.

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