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1.
Artigo em Inglês | MEDLINE | ID: mdl-31924617

RESUMO

The revolution of molecular techniques has revealed that the composition of natural bacterial communities normally includes a few abundant taxa and many rare taxa. Unraveling the mechanisms underlying the spatial assembly process of both abundant and rare bacterial taxa had become a central goal in microbial ecology. Here we used high-throughput sequencing to explore geographic patterns and the relative importance of ecological processes in the assembly of abundant and rare bacterial subcommunities from 25 lakes across the middle and lower reaches of Yangtze River basin (MLYB, located in southeast China), where most of the lakes are interconnected by river networks. We found a similar biogeographic pattern of abundant and rare subcommunities which could significantly separate between the two lake groups that were far from each other, while could not separate among the nearby lakes. Both abundant and rare bacteria followed a strong distance-decay relationship. These findings suggest that the interconnectivity between lakes homogenizes the bacterial communities in local areas, and the abundant and rare taxa therein may be affected by the same ecological process. In addition, based on the measured environmental variables, the deterministic processes explain a small fraction of variation within both abundant and rare subcommunities. While both neutral and null model revealed a high stochasticity ratio for the spatial distribution patterns of both abundant and rare taxa. These findings indicate that the stochastic processes exhibited a greater influence on both abundant and rare bacterial subcommunities assembly among interconnected lakes.Importance The Middle and Lower Yangtze Plain is a typical floodplain, in which many lakes will connect with each other, especially in the wet season. More importantly, with the frequent change of regional water level in the wet season, there is a mutual hydrodynamic exchange among these lakes. The microbial biogeography among these interconnected lakes is still poorly understood. This study aims to unravel the mechanisms underlying the assembly process of abundant and rare bacteria among the interconnected lakes in the Middle and Lower Yangtze Plain. Our findings will provide a deeper understanding of the biogeographic patterns of rare and abundant bacterial taxa and their determined processes among interconnected aquatic habitats.

2.
Acta Pharmacol Sin ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913347

RESUMO

An increasing number of drugs are metabolized by aldehyde oxidase (AOX), but AOX-mediated drug interactions are seldom reported due to the lack of appropriate inhibitors and inducers. A recent study reported that nimesulide (NIM) could increase the liver injury risk of methotrexate. The latter was mainly metabolized by AOX to form hepatotoxic 7-hydroxymethotrexate (7-OH MTX). Thus, we speculated that NIM could induce AOX. In this study, we investigated the potential induction of AOX activity by NIM using methotrexate as the probe substrate. Treatment of primary human and rat hepatocytes with NIM (20 µM) for 24 h caused a 2.0- and 3.1-fold, respectively, increase in 7-OH MTX formation. Oral administration of NIM (100 mg·kg-1·d-1, for 5 days) to rats significantly increased the systematic exposure (6.5-fold), liver distribution (2.5-fold), and excretion (5.2-fold for urinary excretion and 2.1-fold for fecal excretion) of 7-OH MTX. The 7-OH MTX formation in liver cytosol from rats pretreated with 20, 50, and 100 mg·kg-1·d-1 NIM for 5 days increased by 1.9-, 3.2-, and 3.7-fold, respectively, compared with that of rats pretreated with the vehicle. We revealed that the elevation of AOX activity was accompanied by an increase in AOX1 protein levels but not the corresponding mRNA levels. Collectively, our results demonstrate for the first time that NIM can increase the AOX activity of humans and rats, and may raise concerns regarding the risk of drug interactions between NIM and AOX substrates in clinical practice.

3.
Theranostics ; 10(1): 353-370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903125

RESUMO

Background: Long non-coding RNAs (lncRNAs) constitute an important component of the regulatory apparatus that controls stem cell pluripotency. However, the specific mechanisms utilized by these lncRNAs in the control of pluripotency are not fully characterized. Methods: We utilized a RNA reverse transcription-associated trap sequencing (RAT-seq) approach to profile the mouse genome-wide interaction targets for lncRNAs that are screened by RNA-seq. Results: We identified Peblr20 (Pou5F1 enhancer binding lncRNA 20) as a novel lncRNA that is associated with stem cell reprogramming. Peblr20 was differentially transcribed in fibroblasts compared to induced pluripotent stem cells (iPSCs). Notably, we found that Peblr20 utilized a trans mechanism to interact with the regulatory elements of multiple stemness genes. Using gain- and loss-of-function experiments, we showed that knockdown of Peblr20 caused iPSCs to exit from pluripotency, while overexpression of Peblr20 activated endogenous Pou5F1 expression. We further showed that Peblr20 promoted pluripotent reprogramming. Mechanistically, we demonstrated that Peblr20 activated endogenous Pou5F1 by binding to the Pou5F1 enhancer in trans, recruiting TET2 demethylase and activating the enhancer-transcribed RNAs. Conclusions: Our data reveal a novel epigenetic mechanism by which a lncRNA controls the fate of stem cells by trans-regulating the Pou5F1 enhancer RNA pathway. We demonstrate the potential for leveraging lncRNA biology to enhance the generation of stem cells for regenerative medicine.

4.
Theranostics ; 10(2): 829-840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903153

RESUMO

Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as a single agent therapy needs to be improved as resistance is frequently observed. Methods: A tissue microarray was performed to assess ASS1 expression in surgical specimens of pancreatic ductal adenocarcinoma (PDAC) and its correlation with disease prognosis. An RNA-Seq analysis examined the role of ASS1 in regulating the global gene transcriptome. A high throughput screen of FDA-approved oncology drugs identified synthetic lethality between histone deacetylase (HDAC) inhibitors and Arg deprivation in PDAC cells with low ASS1 expression. We examined HDAC inhibitor panobinostat (PAN) and Arg deprivation in a panel of human PDAC cell lines, in ASS1-high and -knockdown/knockout isogenic models, in both anchorage-dependent and -independent cultures, and in multicellular complex cultures that model the PDAC tumor microenvironment. We examined the effects of combined Arg deprivation and PAN on DNA damage and the protein levels of key DNA repair enzymes. We also evaluated the efficacy of PAN and ADI-PEG20 (an Arg-degrading agent currently in Phase 2 clinical trials) in xenograft models with ASS1-low and -high PDAC tumors. Results: Low ASS1 protein level is a negative prognostic indicator in PDAC. Arg deprivation in ASS1-deficient PDAC cells upregulated asparagine synthetase (ASNS) which redirected aspartate (Asp) from being used for de novo nucleotide biosynthesis, thus causing nucleotide insufficiency and impairing cell cycle S-phase progression. Comprehensively validated, HDAC inhibitors and Arg deprivation showed synthetic lethality in ASS1-low PDAC cells. Mechanistically, combined Arg deprivation and HDAC inhibition triggered degradation of a key DNA repair enzyme C-terminal-binding protein interacting protein (CtIP), resulting in DNA damage and apoptosis. In addition, S-phase-retained ASS1-low PDAC cells (due to Arg deprivation) were also sensitized to DNA damage, thus yielding effective cell death. Compared to single agents, the combination of PAN and ADI-PEG20 showed better efficacy in suppressing ASS1-low PDAC tumor growth in mouse xenograft models. Conclusion: The combination of PAN and ADI-PEG20 is a rational translational therapeutic strategy for treating ASS1-low PDAC tumors through synergistic induction of DNA damage.

5.
Medicine (Baltimore) ; 99(2): e18609, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914039

RESUMO

BACKGROUND: Cerebral palsy (CP) is a common disability in children featured with pathological gait and limb function limitation due to muscle weakness. Improving limb function and quality of life is currently considered to be highlighted. Physiotherapy is a chief component of rehabilitation for children with CP, correcting gait and improve walking capacity through muscle strength training. Standard rehabilitation programs for CP have not been determined. Core stability training (CST), which coordinates limb balance via trunk control, is widely used in sports competition. And it is gradually introduced into the rehabilitation of children with cerebral palsy with a positive impact on the patients' gait performance. By screening published literatures, this study aims to conduct a meta-analysis to systematically evaluate the effectiveness and safety of CST in gait of children with CP. METHODS: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on CST in the treatment of children with CP were searched from 6 databases. Moreover, the reference lists of conference papers and included literatures will be manually searched to avoid omissions. Literature screening and data extraction were performed independently by 2 researchers. RCTs carry out the risk of bias analysis evaluation from seven aspects through the Cochrane Collaboration's risk of bias tool. Fixed or random effect model will be performed to analyze the outcomes. When higher heterogeneity occurs (I > 50%), the sensitivity or subgroup analysis will also be conducted to find potential factors. And the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is used for assessing the quality of evidence. RESULTS: The study will evaluate the effect of CST on gait of children with CP from multiple outcomes, including walking speed, endurance, stride length, and safety. CONCLUSION: Based on evidence-based medicine, the conclusion of this study can demonstrate the effectiveness and safety of CST in gait correction for children with CP. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42019134094.

6.
J Exp Clin Cancer Res ; 39(1): 16, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952541

RESUMO

BACKGROUND: Our previous study showed Musashi2 (MSI2) promoted chemotherapy resistance and pernicious biology of pancreatic cancer (PC) by down-regulating Numb and p53. We further explored the novel molecular mechanism involving its oncogenic role in PC development. METHODS: We investigated the potential role and mechanism of MSI2 in EGF-induced EMT in PC in vitro and vivo. RESULTS: EGF enhanced EGFR (epidermal growth factor receptor) phosphorylation, induced EMT and activated ZEB1-ERK/MAPK signaling in 2 PC cells. However, MSI2 silencing reversed EGF stimulated function, including inhibiting EGF-promoted EMT-like cell morphology and EGF-enhanced cell invasion and migration. Meanwhile, MSI2 silencing inhibited EGF-enhanced EGFR phosphorylation at tyrosine 1068 and reversed EGF-induced change of the key proteins in EMT and ZEB1-ERK/MAPK signaling (ZEB1, E-cad, ZO-1, ß-catenin, pERK and c-Myc). Additionally, MSI2 was co-stained and co-immunoprecipitated with ZEB1, pERK and c-Myc in PC cells by IF and co-IP, implying a close interaction between them. In vivo, MSI2 silencing inhibited pancreatic tumor size in situ and distant liver metastases. A close relationship of MSI2 with EMT and ZEB1-ERK/MAPK signaling were also observed in vivo and human PC samples, which coordinately promoted the poor prognosis of PC patients. CONCLUSIONS: MSI2 promotes EGF-induced EMT in PC via ZEB1-ERK/MAPK signaling.

7.
Sci Total Environ ; 706: 135683, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31940722

RESUMO

Shanghai, a metropolitan city in China, has suffered from severe air pollution, especially PM2.5, in the last few years. Up to now the contribution of local emission and regional transport to the formation of haze in Shanghai remains unclear. With an aim to characterize the mechanism of haze formation in Shanghai, the present paper attempted to provide an overview of a tethered balloon-based field campaign. According to the backward trajectories, the air mass traveling slowly from Jiangsu province accounted for the highest PM2.5 concentration (66 ± 20 µg/m3). Seventy vertical profiles of PM2.5, NO, NO2, SO2 and O3 within 1000 m were obtained, through which a comparison study on the characteristics of the vertical distributions of air pollutants on clean days and haze days was conducted. When altitude increased, clearly decreasing pattern of PM2.5, NO, and NO2 was observed during the field campaign. Due to the low atmospheric boundary layer, the diffusion of air pollutants was suppressed, which favored the formation of haze. The results of the generalized additive model revealed NO2 could the most significant factor influencing the vertical distribution of PM2.5 in both clean and haze days. This study provides new insight into the sources and vertical distribution of PM2.5, which could offer references for air pollution modeling.

8.
Anal Chem ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31927916

RESUMO

Protein detection in complicated biological samples requires robust design and violent rinsing. Many recently developed artificial targeting probes, however, often do not possess antibody-like binding strength to endure hush biosensing conditions; while the classic 2-to-1 sandwich binding pattern are unavailable for many targets, often necessitating complicated indirect signal converting mechanism. Here attempt is made to provide novel "covalent" solution to such problems by employing peptide reactivity to form covalent and robust biosensing structure upon target binding. Both the cross-coupling and cleavage of peptide chains are employed to achieve the classic 2-to-1 binding when only one targeting probe is available. Specifically, a targeting probe against the protein and a signaling probe are co-immobilized onto the sensing interface. The ratio between the two probes and their surface density is modulated so that direct cross-linking between the two immobilized probes is suppressed by the average distance between two such probes. Upon protein binding, the protein molecule may bridge that gap by itself. The signaling probe can carry any motif of signal amplification. And here a Cu ion complexed motif, which can exhibit peroxidase-like activity upon electrochemical agitation, is employed multi-purposely, as the catalyst for cross-linking, cleavage and signal amplification. Three non-homologous target proteins can be sensitively quantified in serum-spiked samples while clinical sample detection of one of them is also successful, these results may suggest the potential of the proposed method in clinical application in the future.

9.
Eur J Immunol ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954378

RESUMO

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Whereas much research has focused on its regulation and function of germinal center B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that experimental autoimmune encephalomyelitis (EAE) is exacerbated in LysM Cre+/ - Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4+ Th17 cell response. In addition, LPS-induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the Il-6 (interleukin-6) promotor in macrophages, leading to a suppressed transcription of Il-6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il-6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease. This article is protected by copyright. All rights reserved.

10.
Sci Total Environ ; 699: 134301, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31525544

RESUMO

The concentration, source and composition of dissolved organic matter (DOM) in aquatic ecosystems are associated with land use and hydrological connectivity between terrestrial and aquatic systems. However, direct evidence of the effects of rainfall and land use on the variability of DOM in aquatic ecosystems is very limited. In this study, chromophoric DOM (CDOM) absorption and fluorescence spectroscopy were used to elucidate how rainfall and land use affect the variability of CDOM in the watershed of Lake Tianmu, a key drinking water reservoir in the Yangtze River Delta. The mean values of the fluorescence intensity (Fmax) of parallel factor analysis-derived humic-like components (C1, C3, C6) and tryptophan-like components C5 were higher in the southeastern inflowing river mouths than those downstream of the lake outlet regions. The upstream tributaries were mainly dominated by humic-like materials, while the lake was mainly dominated by protein-like materials. The Fmax values of four humic-like components and two tryptophan-like components all increased significantly as the %woodland decreased, but %anthropogenic land use (%cropland+%urban construction area) increased. The Fmax of the humic-like components at the inflowing tributaries and the lake increased with increasing rainfall during storm events, and the value was especially pronounced at the inflowing river mouths. We concluded that land use and hydrological conditions play an important role in influencing the CDOM source and optical composition, and these findings provide insights for the understanding of aquatic ecosystem metabolism and reservoir water quality management.


Assuntos
Água Potável/química , Monitoramento Ambiental/métodos , Poluição da Água/análise , China , Ecossistema , Análise Fatorial , Fluorescência , Lagos/química , Chuva , Rios , Estações do Ano , Espectrometria de Fluorescência , Poluição da Água/estatística & dados numéricos , Qualidade da Água
11.
J Agric Food Chem ; 68(2): 461-470, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31868356

RESUMO

Contamination of the environment by toxic pesticides has become of great concern in agricultural countries. Chlorpyrifos (CP) is among the pesticides most commonly detected in the environment owing to its wide agricultural applications. The aim of this study was to compare potential changes in the toxicity of CP after irradiation. To this end, photolysis of CP was conducted under simulated sunlight, and neurotoxicity assessment was carried out at CP of 20 and 50 µg L-1 and its corresponding irradiated mixture solutions which contain a mixture of identified intermediates using the nematode, Caenorhabditis elegans as a model organism. Photodegradation of 20 µg L-1 CP for 1 h produced no obvious reduction of physiological damage, and more serious effects on animal movement were detected after exposure of the animals to a solution of 50 µg L-1 for 1 h irradiation compared with unirradiated solution. GABAergic and cholinergic neurons were selectively vulnerable to CP exposure, and maximal neuropathological alterations were observed after 1 h irradiation of the CP solutions in coherence with the behavioral impairment. The generation of photoproducts was considered to be responsible for the enhanced disturbance on those biological processes. This work provided useful information on the toxicological assessments of chemicals that were produced during the environmental transformation of pesticides.

12.
Int J Hyperthermia ; 36(sup1): 74-82, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31795830

RESUMO

Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chemotherapy (CT) or anti-PD-1 antibody in patients with previously treated advanced solid tumors.Materials and methods: Thirty-three (33) patients with ovarian, pancreatic, gastric, colorectal, cervical, or endometrial cancer were recruited into the following therapeutic groups: HT + ACT (n = 10), HT + ACT + anti-PD-1 inhibitor (pembrolizumab) (n = 11) and HT + ACT + CT (n = 12). Peripheral blood was collected to analyze TCR repertoire, measurements of cytokines levels and lymphocyte sub-populations before and after treatment.Results: The objective response rate (ORR) was 30% (10/33), including three complete responses (CR) (9.1%) and seven partial responses (PR) (21.2%) and a disease control rate (DCR = CR + PR + SD) of 66.7% (22 of 33). The most common adverse reactions, blistering, subcutaneous fat induration, local heat-related pain, vomiting and sinus tachycardia, were observed in association with HT. IL-2, IL-4, TNF-α, and IFN-γ levels in peripheral blood were significantly increased among the clinical responders (p < 0.05) while IL-6 and IL-10 were elevated among those with progressive disease (p < 0.05). Peripheral blood CD8+/CD28+ T cells increased (p = 0.002), while the CD4+/CD25+/CD127+Treg cells decreased after therapy (p = 0.012). TCR diversity was substantially increased among the clinical responders.Conclusions: Combining HT with ACT plus either CT or anti-PD-1 antibody was safe, generated clinical responses in previously treated advanced cancers, and promoted TCR repertoire diversity and favorable changes in serum IL-2, IL-4, TNF-α, and IFN-γ levels in clinical responders.

13.
Surg Laparosc Endosc Percutan Tech ; 29(6): 503-508, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31800398

RESUMO

PURPOSE: Few authors have studied applying the laparoscopic approach in patients with previous upper abdominal operations, but no comparison has been made between laparoscopic and open approaches in patients with previous upper abdominal operations. This article aims to introduce surgical techniques and details in treatment to surgeons specialized in minimally invasive surgery. MATERIALS AND METHODS: From January 2010 to January 2018, 460 eligible patients were divided into 3 groups and analyzed retrospectively. Group A: patients with a history of upper abdominal operations who underwent laparoscopy (n=124); group B: patients without a history of upper abdominal operations who underwent laparoscopy (n=140); and group C: patients with a history of upper abdominal operations who underwent an open operation (n=196). Group A was the experimental group; groups B and C served as the control groups. RESULTS: No significant difference was found between groups A and B. Significant differences were found between groups A and C in estimated blood loss (258.3±67.2 vs. 424.7±103.7 mL, P<0.001), postoperative hospitalization (5.7±2.3 vs. 10.2±3.1 d, P<0.001), and postoperative complications (16.1% vs. 42.9%, P=0.013). The final rate of stones clearance was 100% in 3 groups. The total rate of stone recurrence was 7.8%. CONCLUSIONS: Laparoscopy with certain surgical techniques was feasible, effective, and advantageous for patients with previous upper abdominal operations by experienced surgeons. It is necessary for surgeons to have advanced skills and surgical techniques to achieve a successful laparoscopy.

14.
Exp Cell Res ; : 111752, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805277

RESUMO

MicroRNA-501-3p (miR-501-3p) has been reported to play tumor-suppressive roles in different cancers; however, its expression pattern and biological function in non-small cell lung cancer (NSCLC) remain unknown. In this study, we noted downregulation of miR-501-3p in NSCLC tissues and cell lines. Functional assays showed that overexpression of miR-501-3p suppressed NSCLC cell proliferation, clonogenicity, migration, and invasion. Moreover, miR-501-3p overexpression attenuated in vivo tumor growth in a nude mouse model. In terms of the mechanism, RAP1A was identified as a novel target of miR-501-3p. Overexpression of RAP1A strongly attenuated the inhibitory effects of miR-501-3p on the capacity of NSCLC cells for proliferation and motility. In the clinical samples of NSCLC, miR-501-3p levels negatively correlated with RAP1A expression, which was upregulated in NSCLC. Collectively, these results indicate that miR-501-3p acts as a tumor suppressor in NSCLC by directly targeting RAP1A mRNA and may serve as a theranostic biomarker for patients with NSCLC.

15.
J Biol Chem ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806707

RESUMO

Heat shock protein 70 kDa (Hsp70s) are ubiquitous and highly conserved molecular chaperone. They play multiple essential roles in assisting with protein folding and maintaining protein homeostasis. Their chaperone activity has been proposed to require several rounds of binding to and release of polypeptide substrates at the substrate-binding domain (SBD) of Hsp70s. All available structures have revealed a single substrate-binding site in the SBD that binds a single segment of an extended polypeptide of 3 to 4 residues. However, this well-established single peptide-binding site alone has made it difficult to explain the efficient chaperone activity of Hsp70s. In this study, using purified proteins, site-directed mutagenesis, along with fluorescence polarization and luciferase refolding assays, we report the unexpected discovery of a second peptide-binding site in Hsp70s. More importantly, the biochemical analyses suggested that this novel binding site, named here P2, is essential for Hsp70 chaperone activity. Furthermore, cross-linking and mutagenesis studies indicated that this second binding site is in the SBD adjacent to the first binding site. Taken together, our results suggest that these two essential binding sites of Hsp70s cooperate in protein folding.

16.
Front Neurosci ; 13: 1239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824244

RESUMO

Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague-Dawley rats. Motor learning ability was assessed by a beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W + S: 0.81 ± 0.07), PKC (NC9W: 1.66 ± 0.10; DM9W + S: 0.58 ± 0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W + S: 0.63 ± 0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W + S: 0.68 ± 0.04), and NO (NC9W: 135.61 ± 31.91; DM9W + S: 64.06 ± 24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, the outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W + S: 20.47 ± 9.43; DM9W + G: 16.04 ± 7.10). In addition, degeneration and apoptosis were ameliorated, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31851081

RESUMO

OBJECTIVE: Concomitant occurrence of alcoholic chronic pancreatitis (ACP) and alcoholic liver cirrhosis (ALC) is rare with few reported cases. The present study aimed to identify the potential risk factors of chronic pancreatitis (CP) and liver cirrhosis (LC) in ALC patients and ACP patients, respectively. METHODS: A retrospective analysis was performed on 536 patients with CP and 647 ALC patients without CP (Group A). Among the 536 CP patients, 213 ACP cases were divided into two groups: ACP with LC (Group B, n = 52) and ACP without LC (Group C, n = 161). A comparison between Group A and B was carried out to identify the potential risk factors of CP in ALC patients, while Group B and C were compared to determine the independent risk factors of LC in ACP patients. RESULTS: Concomitant occurrence of ACP and ALC accounted for 24.4% (52/213) in this cohort. Significant risk factors for CP in ALC patients included smoking [odds ratio (OR), 2.557; 95% confidence interval (CI): 1.531-5.489; P = 0.003] and multiple bouts of acute pancreatitis (OR, 4.813; 95% CI: 3.625-12.971; P < 0.001). Hepatitis B virus (HBV) infection (OR, 4.237; 95% CI: 1.742-7.629; P = 0.012) was the only independent risk factor associated with LC in ACP patients. CONCLUSION: HBV infection exacerbated liver damage in ACP patients. Alcoholic patients who smoked and suffered from ongoing bouts of acute pancreatitis are prone to develop CP.

18.
Huan Jing Ke Xue ; 40(7): 3018-3029, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854699

RESUMO

Lake Hongze and Lake Luoma are two key lakes located in the middle reaches of the east line of the South-to-North Water Diversion Project. We attempted to unravel the sources and optical composition of CDOM for samples collected from these lakes using excitation-emission matrices (EEMs) and parallel factor analysis (PARAFAC). ① Three fluorescent components were obtained using PARAFAC, including a terrestrial humic-like C1, a tryptophan-like C2, and a tyrosine-like C3. The sources and optical composition of CDOM in the two lakes were, to a large extent, affected by upstream inflow. ② Specifically, fluorescence intensity (Fmax) of the three components C1-C3 in the inflowing river mouths of the two lakes was notably higher than in the other lake regions, and Fmax of the three components during the flood season was significantly higher than during the dry season (t-test, P<0.01). During the flood season, the fluorescence intensity of the terrestrial humic-like component was the highest. This indicates that the source and composition of CDOM in the two lakes are greatly affected by the inflow from the upstream water system, and that the hydrological processes control the abundance and sources of CDOM, especially the terrestrial humic-like C1.③ Significant positive relationships were found between the terrestrial humic-like C1 and the DOC concentrations and CDOM absorption a(254) (r2=0.60, P<0.01; r2=0.88, P<0.01), and the correlation was higher than the other two components. This indicated that the terrestrial humic-like component was the main source of CDOM. In addition, the terrestrial humic-like C1 had a significant positive correlation with SUVA, S275-295, and the integration ratio of the fluorescence peak C to peak T (IC:IT) (r2=0.49, P<0.01; r2=0.61, P<0.01; r2=0.93, P<0.01). It is further revealed that the source and composition of CDOM in the two lakes are greatly affected by land sources. This study reveals the response of CDOM source and composition in Lake Hongze and Lake Luoma to different hydrological scenarios and water transfer processes. Based on these results, the water quality management of the rivers entering the lake should be strengthened during the flood season.

19.
Crit Rev Food Sci Nutr ; : 1-28, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858810

RESUMO

Organic acids are widely utilized in the food industry for inhibiting the activity of polyphenol oxidase (PPO) and enzymatic browning. This review discusses the mechanisms of inhibition of PPO and enzymatic browning by various organic acids based on studies in model systems, critically evaluates the relevance of such studies to real food systems and assesses the implication of the synergistic inhibitory effects of organic acids with other physicochemical processing techniques on product quality and safety. Organic acids inhibit the activity of PPO and enzymatic browning via different mechanisms and therefore the suitability of a particular organic acid depends on the structure and the catalytic properties of PPO and the physicochemical properties of the food matrix. Studies in model systems provide an invaluable insight into the inhibitory mechanisms of various organics acids. However, the difference in the effectiveness of PPO inhibitors between model systems and food systems and the lack of correlation between the degree of PPO inhibition based on in vitro assays and enzymatic browning imply that the effectiveness of organic acids can be accurately evaluated only via direct assessment of browning inhibition in a particular food system. Combination of organic acids with physical processing techniques is one of the most viable approaches for PPO inhibition since the observed synergistic effect helps to reduce the undesirable organoleptic quality changes from the use of excessive concentration of organic acids or intense physical processing.

20.
PLoS One ; 14(12): e0226573, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31846498

RESUMO

Although antiretroviral therapy (ART) has resulted in a marked decrease in AIDS-related morbidity and mortality, the therapeutic benefit is often limited by side effects such as metabolic derangement such as lipodystrophy and hyperlipidemia and cardiovascular diseases. These side effects are pervasive in people living with HIV (PLWH). However, the underlying mechanisms are not completely understood. We investigated the effects of ART on cholesterol biosynthesis genes. This is a retrospective analysis of data and specimens collected during a cross-sectional, case-control study of ART-induced toxicity. Cases were HIV treatment-experienced individuals with HIV viral suppression and no diagnosis of ART-associated toxicity (n = 18), and controls were HIV-uninfected individuals (n = 18). The mRNA expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and ATP binding cassette transporter A1 (ABCA1) were significantly upregulated in cases (HIV+) compared to controls (HIV-), as well as the corresponding protein expression level of HMGCR. We observed dysregulation between sterol regulatory element-binding protein 2 (SREBP-2, sensory control) and HMGCR and low-density lipoprotein receptor (LDLR) pathways. Dysregulation of cholesterol biosynthesis genes may predate clinical manifestation of ART-induced lipid abnormalities.

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