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1.
Org Biomol Chem ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399609

RESUMO

A mild Rh-catalyzed method for synthesis of cyclic unprotected N-Me and N-H 2,3-aminoethers using an olefin aziridination-aziridine ring-opening domino reaction has been developed. The method is readily applicable to the stereocontrolled synthesis of a variety of 2,3-disubstituted aminoether O-heterocyclic scaffolds, including tetrahydrofurans, tetrahydropyrans and chromanes.

2.
Trials ; 22(1): 55, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441157

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an intestinal inflammatory disease characterized by inflammation of the colonic mucosa. With unknown pathogenesis, it has become a chronic lifetime disorder worldwide. In patients with moderately active UC, several therapies (e.g., aminosalicylates, corticosteroids, immunosuppressants, and biologics) are recommended for induction (or maintenance) of remission. Given the side effects and disease burden, it is difficult for most patients to achieve ideal treatment goals in clinical practice. Chinese herbal medicine (CHM), as a complementary therapy, has been widely used in the management of UC in China. Qing-Chang-Hua-Shi granule (QCHS) is a classical Chinese herbal formula. Our preliminary study suggested that the QCHS decoction has a significant effect on patients with moderately active UC. However, its effectiveness and safety has not been evaluated convincingly. Therefore, we designed this protocol to investigate the efficacy of QCHS granule for moderately active UC. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, superiority trial. A total of 120 patients with moderately active UC will be recruited from 10 hospitals in China. Each eligible participant will be randomly assigned to receive QCHS granule or placebo for 12 weeks. Both groups will be given basic treatment with mesalazine (4 g/day). The primary outcomes are the clinical response (remission) rate. The secondary outcomes are health-related quality of life, endoscopic response rate, mucosal healing rate, and inflammatory markers (e.g., fecal calprotectin and CRP). The whole study period will last 36 weeks, including 24 weeks follow-up time. According to the intention-to-treat principle, variables will be assessed at 2, 4, 6, 8, 10, and 12 weeks after study commencement. DISCUSSION: This is the first randomized controlled clinical study protocol regarding Chinese herbal extract granules in the management of moderately active UC. We aim to investigate the superiority of QCHS granules over placebo in terms of induction of remission. If the trial shows significant benefits of QCHS granules, it will help clinical practitioners, UC patients, and policymakers make more informed choices in the decision-making. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-14005554 . Registered on 27 November 2014.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33452641

RESUMO

Microcystins (MCs) have seriously polluted drinking water supplies and have caused great harm to aquatic organisms and humans. Understanding the dynamics of MC concentrations and its influencing factors is necessary for drinking water safety. Many previous studies on MC pollution focused on intracellular MCs rather than on extracellular MCs, which are more difficult to remove by water treatment. So far, the release characteristics of MCs and the relationships between intracellular and extracellular MCs are still unclear. To explore these questions, a survey was conducted at 18 sites across Lake Erhai from May 2014 to April 2015 as in Lake Erhai the frequency and coverage area of cyanobacterial blooms have been increasing. Variation of extracellular MCs lagged behind that of intracellular MCs. The highest value of intracellular MCs was 1.07 µg L-1 in October 2014 and the highest extracellular MC concentration was 0.035 µg L-1 in November 2014. Intracellular MCs were positively influenced by MC-producing cyanobacterial biomass, water temperature (WT), pH, and conductivity (Cond). The extracellular MCs showed little correlation with cyanobacterial abundances and intracellular MC concentrations, but showed significant negative correlations with WT, pH, and Cond. These results indicated that high biomass and high intracellular MC concentrations did not quickly lead to large releases of MCs, and that when cyanobacterial cells died and blooms disappeared, MCs were intensively released into the water, posing the greatest threat to drinking water supply.

4.
J Phys Chem B ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397114

RESUMO

The rigid-body fitting of predicted structural models into cryo-electron microscopy (cryo-EM) density maps is a necessary procedure for density map-guided protein structure determination and prediction. We proposed a novel multiobjective optimization protocol, MOFIT, which performs a rigid-body density-map fitting based on particle swarm optimization (PSO). MOFIT was tested on a large set of 292 nonhomologous single-domain proteins. Starting from structural models predicted by I-TASSER, MOFIT achieved an average coordinate root-mean-square deviation of 2.46 Å, which was 1.57, 2.79, and 3.95 Å lower than three leading single-objective function-based methods, where the differences were statistically significant with p-values of 1.65 × 10-6, 6.36 × 10-8, and 6.44 × 10-11 calculated using two-tail Student's t tests. Detailed analyses showed that the major advantages of MOFIT lie in the multiobjective protocol and the extensive PSO search simulations guided by the composite objective functions, which integrates complementary correlation coefficients from the global structure, local fragments, and individual residues with the cryo-EM density maps.

5.
J Mol Neurosci ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403589

RESUMO

Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.

6.
Proteins ; 89(2): 242-250, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32935893

RESUMO

A major challenge for protein databases is reconciling information from diverse sources. This is especially difficult when some information consists of secondary, human-interpreted rather than primary data. For example, the Swiss-Prot database contains curated annotations of subcellular location that are based on predictions from protein sequence, statements in scientific articles, and published experimental evidence. The Human Protein Atlas (HPA) consists of millions of high-resolution microscopic images that show protein spatial distribution on a cellular and subcellular level. These images are manually annotated with protein subcellular locations by trained experts. The image annotations in HPA can capture the variation of subcellular location across different cell lines, tissues, or tissue states. Systematic investigation of the consistency between HPA and Swiss-Prot assignments of subcellular location, which is important for understanding and utilizing protein location data from the two databases, has not been described previously. In this paper, we quantitatively evaluate the consistency of subcellular location annotations between HPA and Swiss-Prot at multiple levels, as well as variation of protein locations across cell lines and tissues. Our results show that annotations of these two databases differ significantly in many cases, leading to proposed procedures for deriving and integrating the protein subcellular location data. We also find that proteins having highly variable locations are more likely to be biomarkers of diseases, providing support for incorporating analysis of subcellular location in protein biomarker identification and screening.

7.
Sci Total Environ ; 755(Pt 2): 142631, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33065505

RESUMO

This study aimed to assess earthworm's capability of reducing the bioavailability of cadmium (Cd) in soil and increasing soil fertility with the modification of seasonal variations of ambient temperatures on the efficacy of vermiremediation. Earthworms were exposed in soil fortified with 0, 5, 10, and 20 mg Cd kg-1, for 7, 14 and 21 days in winter and spring. The bioavailability of Cd in soil, which is represented in the form of diethylenetriaminepentaacetic acid-extractable fraction (DTPA-Cd), were significantly reduced, ranging from 7.9 to 18.3% in winter and 8.8 to 20.8% in spring. Meanwhile, we found earthworm activities could significantly improve the soil fertility as the results of increasing the availability of nitrogen, phosphorous, and potassium in soil, a prominent advantage of vermiremediation in heavy metal-contaminated soil. Although seasonality could increase Cd toxicity in earthworms, higher ambient temperature in spring season also promoted the reduction of Cd bioavailability and the increase of soil fertility, due to significant increase of microbial populations. In conclusion, we reported the dual beneficial effects of vermiremediation in reducing bioavailability of Cd in soil and simultaneously improving soil fertility in which both outcomes were modified by seasonality.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Disponibilidade Biológica , Cádmio/análise , Solo , Poluentes do Solo/análise
8.
Huan Jing Ke Xue ; 42(1): 211-220, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372473

RESUMO

Owing to the long residence times of water, water reservoirs readily contribute to the accumulation of antibiotic resistant gene (ARG). It is of great public health significance to explore bacterial communities, antibiotic resistomes, and the potential public health risks of water reservoirs. In this study, metagenomic sequencing was used to analyze and compare the bacterial communities, ARG profiles, ARG-horizontal transfer, and ARG-carrying pathogens in the water and sediments of the Dongping Lake Reservoir in the dry and the wet seasons. Compared with that of the sediments, the results showed that both the bacterial communities and ARG profiles in the water were significantly influenced by the seasons, and the total ARG abundance in the dry season was significantly higher than that in the wet season. The total ARG abundance in the sediments was higher than that in water, but the horizontal transfer potential of ARG in the water was higher than that in the sediment. A total of 377 ARG subtypes belonging to 20 ARG types were found in this study. Bacitracin and vancomycin resistance genes were the main ARG types in the water and sediments, respectively, and Proteobacteria and Actinobacteria were the major ARG-carrying bacteria in the water and sediments, respectively. In addition, 30 clinical pathogens carrying ARGs were identified, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica, and Acinetobacter bohemicus. More importantly, two Escherichia coli concurrently carried virulence factor and ARG. In summary, this study revealed that a variety of ARG types existed in the Dongping Lake Reservoir, which has posed potential public health risks by contributing to the horizontal transfer of ARG and the accumulation of clinical pathogens. Therefore, it is necessary to regularly monitor the bacterial community and ARG profile in various water bodies.


Assuntos
Antibacterianos , Lagos , Acinetobacter , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Sedimentos Geológicos , Saúde Pública
9.
J Med Chem ; 64(1): 644-661, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33356246

RESUMO

The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis. A novel series of compounds, exemplified by 2,2-difluoroethyl (3S)-3-{[2'-amino-5-fluoro-2-(morpholin-4-yl)-4,5'-bipyrimidin-6-yl]amino}-3-(hydroxymethyl)pyrrolidine-1-carboxylate (1) (PF-06843195), with high PI3Kα potency and unique PI3K isoform and mTOR selectivity were discovered. We describe here the details of the design and synthesis program that lead to the discovery of 1.

10.
Talanta ; 222: 121449, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33167199

RESUMO

Activated polymorphonuclear neutrophils play an important role in host defense system against invading pathogens via releasing reactive oxygen species through respiratory bursts. Nowadays, neutrophil activation process has been found to be modeled as a two-stages continuum from dormant to primed, and to fully activated. Although the differences of salivary and circulatory neutrophils have been investigated in various experimental designs, priming state of salivary polymorphonuclear neutrophils with respiratory burst has not been comprehensively studied. Here, for the first time so far, a programmable flow injection analysis based on Stop in Flow Cell operation mode has been applied to batch analyzing comparative study of neutrophil activation. The high-sensitivity luminol-dependent chemiluminescence assay has been employed with just 330 µL of cell suspension consumption per sample, and the process has been conducted rapidly and efficiently within 15 min to keep the neutrophils viability. ROS from either unstimulated or substimulated or stimulated salivary polymorphonuclear neutrophils, in comparison with those from autologous circulatory polymorphonuclear neutrophils, have been determined, together with further monitoring the impact of extracellular and intracellular calcium ion (Ca2+) on neutrophils ROS generation. Conclusively, the priming state of salivary polymorphonuclear neutrophils during activation has been testified from multiple aspects.

11.
J Pharm Sci ; 110(1): 404-411, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33058892

RESUMO

Recent studies have focused on coproporphyrin (CP)-I and CP-III (CPs) as endogenous biomarkers for organic anion transporting polypeptides (OATPs). Previous data showed that CPs are also substrates of multidrug resistance-associated protein (MRP/Mrp) 2 and 3. This study was designed to examine the impact of loss of Mrp2 function on the routes of excretion of endogenous CPs in wild-type (WT) Wistar compared to Mrp2-deficient TR- rats. To exclude possible confounding effects of rat Oatps, the transport of CPs was investigated in Oatp-overexpressing HeLa cells. Results indicated that CPs are substrates of rodent Oatp1b2, and that CP-III is a substrate of Oatp2b1. Quantitative targeted absolute proteomic (QTAP) analysis revealed no differences in Oatps, but an expected significant increase in Mrp3 protein levels in TR- compared to WT rat livers. CP-I and CP-III concentrations measured by LC-MS/MS were elevated in TR- compared to WT rat liver, while CP-I and CP-III estimated biliary clearance was decreased 75- and 840-fold in TR- compared to WT rats, respectively. CP-III concentrations were decreased 14-fold in the feces of TR- compared to WT rats, but differences in CP-I were not significant. In summary, the disposition of CPs was markedly altered by loss of Mrp2 and increased Mrp3 function as measured in TR- rats.

12.
J Pharm Biomed Anal ; 192: 113665, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33120311

RESUMO

Cicadae Periostracum (CP), the cast-off shell of Cryptotympana atrata, is specified in Chinese Pharmacopoeia for relieving fever and eliminating ulcer. N-acetyldopamine oligomers are the major characteristic bioactive components with antioxidant and anti-inflammatory activities that may be responsible for the efficacy of CP. However, the exposed components and metabolites of N-acetyldopamine oligomers of CP (NOCP) in vivo are still unknown. In present study, the metabolic profile of total NOCP and N-acetyldopamine dimer B in rats were systematically investigated by ultra-high liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In biosamples of NOCP group, 34 prototypes and 15 metabolites were identified or tentatively characterized, including 5 metabolites in plasma, 3 prototype and 9 metabolites in urine, 2 metabolites in bile, 34 prototypes and 8 metabolites in feces, respectively. In dimer B group, the prototype and 8 metabolites were identified, including 2 metabolites in plasma, 4 metabolites in urine, 1 metabolite in bile and 5 metabolites in feces, respectively. Oxidation, and hydrogenation were supposed to be the major phase I reactions, while methylation, sulfation, and glucuronidation were the main phase II reactions of NOCP and dimer B. M10 and M13 might undergo enterohepatic circulation in rats. It is concluded that NOCP and dimer B were mainly absorbed in the form of metabolites, and metabolites are probably the major bioactive forms of NOCP and dimer B. The outcomes of this study provided helpful information for extensively elucidating biological and pharmacological mechanisms of NOCP.

13.
J Pharm Sci ; 110(1): 376-387, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33122051

RESUMO

Hepatic uptake clearance has been measured in suspended human hepatocytes (SHH). Plated human hepatocytes (PHH) after short-term culturing are increasingly employed to study hepatic transport driven mainly by its higher throughput. To know pros/cons of both systems, the hepatic uptake clearances of several organic anion transporting polypeptide 1B substrates were compared between PHH and SHH by determining the initial uptake velocities or through dynamic model-based analyses. For cerivastatin, pitavastatin and rosuvastatin, initial uptake clearances (PSinf) obtained using PHH were comparable to those using SHH, while cell-to-medium concentration (C/M) ratios were 2.7- to 5.4-fold higher. For pravastatin and dehydropravastatin, hydrophilic compounds with low uptake/cellular binding, their PSinf and C/M ratio in PHH were 1.8- to 3.2-fold lower than those in SHH. These hydrophilic substrates are more prone to wash-off during the uptake study using PHH, which may explain the apparently lower uptake than SHH. The C/M ratios obtained using PHH were stable over an extended time, making PHH suitable to estimate the C/M ratios and hepatocyte-to-medium unbound concentration ratios (Kp,uu). In conclusion, PHH is useful in evaluating hepatic uptake/efflux clearances and Kp,uu of OATP1B substrates in a high-throughput manner, however, a caution is warranted for hydrophilic drugs with low uptake/cellular binding.

14.
Ecotoxicol Environ Saf ; 207: 111538, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254400

RESUMO

Limited information is available about the bio-methylation of inorganic mercury (iHg) under aerobic conditions. In this study, two γ-proteobacteria strains (P. fluorescens TGR-B2 and P. putida TGR-B4) were obtained from the soil of The Three Gorges Reservoir (TGR), demonstrating effective aerobic transformation capacities of iHg into methylmercury (MeHg). Based on periodical changes in soil oxygen content of the TGR, a culture system was established, in which 300 ng Hg (II) L-1 and O2 were set at 7%, 14%, and 21%, respectively. Results indicated that the two strains differed significantly in bacterial growth rate and MeHg production. The kinetic model of MeHg showed typical characteristics of a "two-staged" process: The first stage was dominated by bio-methylation, which was shown by increasing of net MeHg content. Moreover, the second stage was dominated by bio-demethylation, which decreased net MeHg content. Thus, we hypothesized that the mechanism of aerobic bacterial iHg bio-methylation: (1) should inefficiency compared to anaerobic bacteria i.e.SRB, which were regulated by hgcA/B gene clusters, (2) might be regarded as a passive stress response and depended on the bacterial iHg intoxication threshold and MeHg tolerance threshold.


Assuntos
Bactérias Aeróbias/metabolismo , Mercúrio/metabolismo , Poluentes do Solo/metabolismo , Monitoramento Ambiental , Mercúrio/análise , Metilação , Compostos de Metilmercúrio , Oxigênio , Solo , Poluentes do Solo/análise
15.
J Ethnopharmacol ; 266: 113394, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32941971

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract, consisting of ulcerative colitis (UC) and Crohn's disease (CD). Gut microbiota and their metabolites may play a role in the pathogen of IBD, especially of the UC. Qingchang Huashi Formula (QHF), a traditional Chinese medicine formula, has shown therapeutic effect on treating UC based on the clinical practice without clear pharmacological mechanism. AIM OF THE STUDY: The aim of this study was to clearly define the effect of QHF and its components, Baitouweng (PBR) and Baizhi (ADR) on treating UC. MATERIALS AND METHODS: Pharmacodynamic effects of QHF and single herb were evaluated in dextran sulfate sodium (DSS) induced acute or chronic colitis mice. Body weight loss, disease activity index (DAI) and colon length were estimated. Histological changes were observed by H&E staining. The number and abundance of gut microbiota were measured with 16S rRNA sequencing. LC-MS and GC-MS were used to detect the concentration of metabolites (e.g., bile acids (BAs) and short chain fatty acids (SCFAs)). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining and the crypt stem cell was estimated by immunohistochemical analyses. The colorectal tissues were used to detect levels of IL-1ß, IL-6 and TNF-α by ELISA or qRT-PCR. The expression of NLRP3, Caspase 1 and IL-1ß were examined by western blotting. RESULTS: QHF significantly inhibited colitis, protected mice from the loss of body weight and colon shorten. Comparatively, ADR and PBR showed strong efficacy in inhibiting DSS-induced colitis. We verified that while ADR was responsible for QHF's effect on maintaining gut microbiota homeostasis and metabolism, PBR was more prominent in keeping crypt stem cells proliferation and colonic goblet cells function. Moreover, we demonstrated that the alleviation of colitis by QHF was associated with the restoration of gut microbiota-metabolism homeostasis, protection of intestinal epithelial barrier and regulation of NLRP3/IL-1ß pathway. CONCLUSIONS: The finding of the present study suggested that QHF is curative in DSS-induced colitis by restoring gut microbiota-metabolism homeostasis and goblet cells function. An optimized QHF was constituted by ADR and PBR, which showed comparable efficacy on colitis to that of QHF. Our work probed out the active constitutes as well as the relevant pharmacological mechanisms of QHF, shedding light on potential new drug combination for the treatment of IBD.

16.
J Pharmacol Exp Ther ; 376(1): 29-39, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33127749

RESUMO

Expression and functional changes in the organic anion transporting polypeptide (OATP)-multidrug resistance-associated protein (MRP) axis of transporters are well reported in patients with nonalcoholic steatohepatitis (NASH). These changes can impact plasma and tissue disposition of endo- and exogenous compounds. The transporter alterations are often assessed by administration of a xenobiotic or by transporter proteomic analysis from liver biopsies. Using gene expression, proteomics, and endogenous biomarkers, we show that the gene expression and activity of OATP and MRP transporters are associated with disease progression and recovery in humans and in preclinical animal models of NASH. Decreased OATP and increased MRP3/4 gene expression in two cohorts of patients with steatosis and NASH, as well as gene and protein expression in multiple NASH rodent models, have been established. Coproporphyrin I and III (CP I and III) were established as substrates of MRP4. CP I plasma concentration increased significantly in four animal models of NASH, indicating the transporter changes. Up to a 60-fold increase in CP I plasma concentration was observed in the mouse bile duct-ligated model compared with sham controls. In the choline-deficient amino acid-defined high-fat diet (CDAHFD) model, CP I plasma concentrations increased by >3-fold compared with chow diet-fed mice. In contrast, CP III plasma concentrations remain unaltered in the CDAHFD model, although they increased in the other three NASH models. These results suggest that tracking CP I plasma concentrations can provide transporter modulation information at a functional level in NASH animal models and in patients. SIGNIFICANCE STATEMENT: Our analysis demonstrates that multidrug resistance-associated protein 4 (MRP4) transporter gene expression tracks with nonalcoholic steatohepatitis (NASH) progression and intervention in patients. Additionally, we show that coproporphyrin I and III (CP I and III) are substrates of MRP4. CP I plasma and liver concentrations increase in different diet- and surgery-induced rodent NASH models, likely explained by both gene- and protein-level changes in transporters. CP I and III are therefore potential plasma-based biomarkers that can track NASH progression in preclinical models and in humans.

17.
J Ethnopharmacol ; 269: 113722, 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33352240

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Poria) is a well-known traditional medicinal fungus. It has been considered to possess spleen-invigorating (Jianpi) effects in traditional Chinese medicine, and is used clinically to treat spleen deficiency (Pixu) with symptoms of intestinal disorders such as diarrhea, indigestion, mucositis and weight loss. THE AIM OF THIS STUDY: To investigate the protective effects of Poria and its three component fractions (Water-soluble polysaccharides, WP; alkali-soluble polysaccharides, AP; triterpene acids, TA) on cisplatin-induced intestinal injury and explore the underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were treated with Poria powder (PP), WP, AP and TA by oral gavage respectively for 13 days, and intraperitoneally injected with 10 mg/kg of cisplatin on day 10 to conduct a cisplatin-induced intestinal injury model. Pathological changes of ileum and colon were examined using H&E staining. The composition of gut microbiota and the alteration of host metabolites were characterized by 16S rDNA amplicon sequencing and UPLC-QTOF-MS/MS based untargeted metabolomics analysis. RESULTS: PP and WP attenuated the cisplatin-induced ileum and colon injury, and WP alleviated the weight loss and reversed the elevation of IL-2, IL-6 in serum. Both PP and WP could mitigate cisplatin-induced dysbiosis of gut microbiota, in particular PP and WP decreased the abundance of pathogenic bacteria including Proteobacteria, Cyanobacteria, Ruminococcaceae and Helicobacteraceae, while WP promoted the abundance of probiotics, such as Erysipelotrichaceae and Prevotellaceae. Moreover, WP attenuated the cisplatin-induced alteration of metabolic profiles. The levels of potential biomarkers, including xanthine, L-tyrosine, uridine, hypoxanthine, butyrylcarnitine, lysoPC (18:0), linoleic acid, (R)-3-hydroxybutyric acid, D-ribose, thiamine monophosphate, indolelactic acid and plamitic acid, showed significant correlations with intestinal flora. CONCLUSIONS: PP and WP possess protective effects against cisplatin-induced intestinal injury via potentially regulating the gut microbiota and metabolic profiles.

18.
J Orthop Surg (Hong Kong) ; 28(3): 2309499020975213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33355038

RESUMO

PURPOSE: The study aimed to develop an evidence-based expert consensus statement on diagnosis and treatment of cervical ossification posterior longitudinal ligament (OPLL). METHOD: Delphi method was used to perform such survey, and the panel members from Asia Pacific Spine Society (APSS) 2020 were invited to answer the open-ended questions in rounds 1 and 2. Then the results were summarized and developed into a Likert-style questionnaire for voting in round 3, and the level of agreement was defined as 80%. In the whole process, we conducted a systematic literature search on evidence for each statement. RESULTS: Cervical OPLL can cause various degrees of neurological symptoms, an it's thought to be more common in Asia population. CT reconstruction is an important imaging examination to assist diagnosis and guide surgical choice. Segmental, continuous, mixed, and focal type is the most widely used classification system. The non-surgical treatment is recommended for patients with no or mild clinical symptoms, or irreversible neurological damage, or failed surgical decompression, or condition cannot tolerant surgery, or refusing surgery. As OPLL may continue to develop gradually, surgical treatment would be considered in their course inevitably. The surgical choice should depend on various conditions, such as involved levels, thickness, and type of OPLL, skill-experiences of surgeons, which are listed and discussed in the article. CONCLUSION: In this statement, we describe the clinical features, classifications, and diagnostic criteria of cervical OPLL, and review various surgical methods (such as their indications, complications), and provide a guideline on their choice strategy.

19.
Environ Res ; 193: 110587, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33307080

RESUMO

The MXene-based transition metal oxide composite is a potential candidate for photocatalysts. Rod-like pseudohexagonal phase Nb2O5/Nb2CTx composites were synthesized by a simple hydrothermal oxidation of 2D layered Nb2CTx. The Nb2O5/Nb2CTx composites show superior photocatalytic activity for 98.5% of degradation of Rhodamine B (RhB) for 120 min and 91.2% of tetracycline hydrochloride (TC-HCl) for 180 min under visible light irradiation. The Schottky junction is formed between Nb2O5 nanorods and Nb2CTx and the photo-generated carriers are effectively separated, enhancing the photocatalytic activity of the Nb2O5/Nb2CTx. High photoactivity and cycle stability of Nb2O5/Nb2CTx composites indicate that hydrothermal oxidation of 2D layered Nb2CTx is an alternative to prepare efficient photocatalyst for degradation of organic pollutants.

20.
Nutrients ; 12(12)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302352

RESUMO

Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (ß coefficient = -2.705, p < 0.001) but positively associated with intervention (ß coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.

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