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1.
Food Chem ; 315: 126270, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32028199

RESUMO

An electrochemistry coupled to online quadrupole time-of-flight tandem mass spectrometry (EC/Q-TOF/MS) was applied to investigate the oxidative transformation and metabolic pathway of five phenolic acids in Danshen sample. Simulation of the phase I oxidative metabolism was carried out in an electrochemical reactor equipped with a glassy carbon working electrode. The phase II reactivity of the generated oxidative products towards biomolecules (such as glutathione) was investigated by ways of covalent adduct formation experiments. The results obtained by EC/MS were compared with well-known in vitro studies by conducting rat liver microsome incubations. Structures of the electrochemically produced metabolites were identified by accurate mass measurement and previously results in vivo metabolites. It was indicated that the electrochemical oxidation was in good accordance with similar products found in vivo experiments. In conclusion, this work confirmed that EC/Q-TOF/MS was a promising analytical tool in the prediction of metabolic transformations of functional foods.

2.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32013003

RESUMO

The crystal structure of the sorafenib and B-RAF complex indicates that the binding cavity occupied by the pyridine-2-carboxamide in sorafenib has a large variable space, making it a reasonable modification site. In order to identify novel compounds with anti-cancer activity, better safety and polar groups for further application, five sorafenib analogs with new pyridine-2-amide side chains were designed and synthesized. Preliminary pharmacologic studies showed that these compounds displayed much lower toxicities than that of sorafenib. Among them, compound 10b bearing mercaptoethyl group kept relevant antiproliferation potency compared to sorafenib in Huh7 and Hela cell lines with values of IC50 58.79 and 63.67 M, respectively. As a small molecule inhibitor targeting protein tyrosine kinases, thiol in compound 10b would be an active group to react with maleimide in a mild condition for forming nanoparticles Sorafenib-PEG-DGL, which could be developed as a delivery vehicle to improve the concentration of anti-tumor therapeutic agents in the target cancer tissue and reduce side effects in the next study.

3.
AIDS Care ; : 1-9, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008356

RESUMO

China's HIV/AIDS epidemic continues to grow in rural and less developed areas. This consecutive cross-sectional study examines demographic and behavioral factors associated with HIV/STI infection, Hepatitis C (HCV) and other sexually transmitted infections (STIs) among Vietnamese female sex workers (FSW), a vulnerable population who cross into Guangxi, China. This study is a secondary data analysis of 303 Vietnamese and 4,348 Chinese FSWs recruited over seven years from two Chinese counties that border Vietnam. Logistic regression models compared demographics, HIV/STI status, HIV/AIDS-related knowledge, attitudes, and risk behaviors between Vietnamese FSWs and Chinese FSWs. Compared with Chinese FSWs, Vietnamese FSWs were younger, had attained lower education levels, were highly mobile, more likely to report using drugs, and were more vulnerable to HIV/STIs. Younger age, less educational attainment, shorter time in their current working location, no voluntary HIV testing in the last year, greater drug use, and not using condoms for all commercial sex in the last month were associated with higher HIV/STIs. In conclusion, several factors were associated with HIV/STI risk in Vietnamese cross-border FSWs. There is a pressing need to improve support systems for Vietnamese cross-border FSW and health system cooperation across the Chinese/Vietnamese border.

4.
AIDS Res Ther ; 17(1): 4, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033564

RESUMO

OBJECTIVES: For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. METHODS: Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. RESULTS: Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. CONCLUSION: FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.

5.
Parasit Vectors ; 13(1): 56, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046772

RESUMO

BACKGROUND: Eimeria spp. are responsible for chicken coccidiosis which is the most important enteric protozoan disease resulting in tremendous economic losses in the poultry industry. Understanding the interaction between the avian cecal microbiota and coccidia is of interest in the development of alternative treatments that do not rely on chemotherapeutics and do not lead to drug resistance. METHODS: We utilized 16S rRNA gene sequencing to detect the dynamics of the cecal microbial community in AA broilers challenged with Eimeria tenella. Histopathological analysis of the cecum was also conducted. RESULTS: We found that microbial shifts occur during the infection. Lactobacillus, Faecalibacterium, Ruminococcaceae UCG-013, Romboutsia and Shuttleworthia decreased in abundance. However, the opportunistic pathogens Enterococcus and Streptococcus increased in abundance over time in response to the infection. CONCLUSIONS: Eimeria tenella disrupts the integrity of the cecal microbiota and could promote the establishment and growth of potentially pathogenic bacteria. Defining bacterial populations affected by coccidial infection might help identify bacterial markers for intestinal disease as well as populations or species that could be beneficial in maintaining and restoring gut homeostasis during and after infection with E. tenella.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32030889

RESUMO

AIM: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). METHODS: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy-three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next-generation sequencing. Genetic and biological features and their association with survival were evaluated. RESULTS: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1-16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9-12.8) than those with non-vCK (16.1 months with 95% CI 11.5-20.8) (P = .02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5-11.5 vs 26.1 months with 95% CI 8.0-44.2, P < .01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild-type TP53 (60% vs 22.2%, P = .03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P = .03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. CONCLUSIONS: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors.

7.
J Microbiol ; 58(2): 142-152, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31993988

RESUMO

Pleurotus pulmonarius, a member of the Pleurotaceae family in Basidiomycota, is an edible, economically important mushroom in most Asian countries. In this study, the complete mitochondrial genomes (mtDNA) of three P. pulmonarius strains - two monokaryotic commercial (J1-13 and ZA3) and one wild (X1-15) - were sequenced and analyzed. In ZA3 and X1-15, the mtDNA molecule was found to be a single circle of 68,305 bp and 73,435 bp, respectively. Both strains contain 14 core protein-coding genes and two ribosomal RNA (rRNA) subunit genes. The ZA3 strain has 22 transfer RNA (tRNA) genes and nine introns: eight in cytochrome c oxidase subunit 1 (coxl), and one in the rRNA large subunit (rnl). Monokaryotic J1-13 and ZA3 mtDNAs were found to be similar in their structure. However, the wild strain X1-15 contains 25 tRNA genes and only seven introns in coxl. Open reading frames (ORFs) of ZA3/J1-13 and X1-15 encode LAGLIDADG, ribosomal protein S3, and DNA polymerase II. In addition, mtDNA inheritance in J1-13, ZA3, and X1-15 was also studied. Results showed that the mtDNA inheritance pattern was uniparental and closely related to dikaryotic hyphal location with respect to the parent. Results also show that mtDNA inheritance is influenced by both the parental nuclear genome and mitogenome in the zone of contact between two compatible parents. In summary, this analysis provides valuable information and a basis for further studies to improve our understanding of the inheritance of fungal mtDNA.

8.
Cell Biol Int ; 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31903671

RESUMO

In vivo regeneration of lost or dysfunctional islet ß cells can fulfill the promise of improved therapy for diabetic patients. To achieve this, many mitogenic factors have been attempted, including gamma-aminobutyric acid (GABA). GABA remarkably affects pancreatic islet cells' (α cells and ß cells) function through paracrine and/or autocrine binding to its membrane receptors on these cells. GABA has also been studied for promoting the transformation of α cells to ß cells. Nonetheless, the gimmickry of GABA-induced α-cell transformation to ß cells has two different perspectives. On the one hand, GABA was found to induce α-cell transformation to ß cells in vivo and insulin-secreting ß-like cells in vitro. On the other hand, GABA treatment showed that it has no α- to ß-cell transformation response. Here, we will summarize the physiological effects of GABA on pancreatic islet ß cells with an emphasis on its regenerative effects for transdifferentiation of islet α cells to ß cells. We will also critically discuss the controversial results about GABA-mediated transdifferentiation of α cells to ß cells.

9.
Antiviral Res ; 174: 104704, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917237

RESUMO

AIMS: Deguelin, a natural compound derived from Mundulea sericea (Leguminosae) and some other plants exhibits an activity to inhibit autophagy, a cellular machinery required for hepatitis C virus (HCV) replication. This study aimed to illuminate the impact of deguelin on HCV replication and mechanism(s) involved. METHODS: HCV JFH-1-Huh7 infectious system was used for the investigation. Real time RT-PCR, Western blot, fluorescent microscopy assay were used to measure the expression levels of viral or cellular factors. Overexpression and silencing expression techniques were used to determine the role of key cellular factors. RESULTS: Deguelin treatment of Huh7 cells significantly inhibited HCV JFH-1 replication in a dose- and time-dependent manner. Deguelin treatment suppressed autophagy in Huh7 cells, evidenced by the decrease of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the increase of p62 level in deguelin-treated cells compared with control cells. HCV infection could induce autophagy which was also suppressed by deguelin treatment. Mechanism research reveals that deguelin inhibited expression of Beclin1, which is a key cellular factor for the initiation of the autophagosome formation in autophagy. Overexpression or silencing expression of Beclin1 in deguelin-treated Huh7 cells could weaken or enhance the inhibitory effect on autophagy by deguelin, respectively, and thus partially recover or further inhibit HCV replication correspondingly. CONCLUSIONS: Deguelin may serve as a novel anti-HCV compound via its inhibitory effect on autophagy, which warrants further investigation as a potential therapeutic agent for HCV infection.

10.
J Pharm Biomed Anal ; 180: 113071, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31931323

RESUMO

The zirconium metal-organic framework (Zr-MOF) was used as a novel and effective adsorbent material for the enrichment of five phenylurea herbicides (fenuron, monuron, diuron, linuron and pencycuron) in natural products. The target analytes were determined by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Some crucial experimental parameters, such as type of adsorbents, amount of adsorbent, type of eluent solvents and adsorption capacity were investigated and optimized. Under the optimum extraction conditions, the enrichment factors of fenuron, monuron, diuron, linuron and pencycuron were 90, 128, 148, 204 and 295 times, respectively. A good linearity was obtained in different concentration levels of target analytes with the determination coefficients (r2) larger than 0.993. In addition, the limits of detection varied from 0.05 to 0.36 ng/mL and the recoveries of the analytes were in the range of 85.19-99.13 %. The results demonstrated that the proposed miniaturized solid-phase extraction procedure coupled with Zr-MOF could become an effective tool to analyze phenylurea herbicides and would have the vast application prospect for the extraction of pesticide residue and more organic pollutants from Hawthorn, Dendrobii Officinalis Caulis and Salviae Miltiorrhizae Radix et Rhizoma samples.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31986004

RESUMO

MicroRNAs (miRNAs) therapy has shown to have great promise for the treatment of androgen-independent prostate cancer (AIPC) due to the low efficiency of hormonal therapy. However, instability of RNA and inefficiency of RNA therapy limit the use of miRNAs in the treatment of AIPC. Here, we report a pH/ATP-activated nanocomplexes for increasing cytosolic delivery of miR146a which can effectively inhibit the expression of epidermal growth factor receptor (EGFR) in AIPC. The nanocomplexes show identical suppressing effect in invasion, colony formation, migration ability, and growth of DU145 cells compared with Lipofectamine 2000 (lipo). But for in vivo experiments, the nanocomplexes vigorously suppress the growth of tumor volumes comparing to lipo group after five weeks' treatment. These results demonstrate the potential of the pH/ATP-activated nanocarriers for AIPC gene therapy.

12.
Environ Pollut ; 256: 113471, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677878

RESUMO

Bacteria with arsenate-reducing (ars) and arsenite-oxidizing (aio) genes usually co-exist in aerobic environments, but their contrast impacts on arsenic (As) speciation and mobility remain unclear. To identify which kind of bacteria dominate As speciation under oxic conditions, we studied the biotransformation of adsorbed As on goethite in the co-existence of Pantoea sp. IMH with ars gene and Achromobacter sp. SY8 with aio gene. The incubation results show that SY8 dominated the dissolved As speciation as As(V), even though aio exhibited nearly 5 folds lower transcription levels than ars in IMH. Nevertheless, our XANES results suggest that SY8 showed a negligible effect on solid-bound As speciation whereas IMH reduced adsorbed As(V) to As(III). The change in As speciation on goethite surfaces led to a partial As structural change from bidentate corner-sharing to monodentate corner-sharing as evidenced by our EXFAS analysis. Our Mössbauer spectroscopic results suggest that the incubation with SY8 reduced the degree of crystallinity of goethite, and the reduced crystallinity can be partly compensated by IMH. The changes in As adsorption structure and in goethite crystallinity had a negligible effect on As release. The insights gained from this study improve our understanding of biotransformation of As in aerobic environment.

13.
Electrophoresis ; 41(1-2): 123-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31674686

RESUMO

A novel micro matrix solid phase dispersion method was successfully used for the extraction of quaternary alkaloids in Phellodendri chinensis cortex. The elution of target compounds was accomplished with sodium hexanesulfonate as the eluent solvent. A neutral ion pair was formed between ion-pairing reagent and positively charged alkaloids in this process, which was beneficial for selectively extraction of polar alkaloids. Several parameters were optimized and the optimal conditions were listed as follows: silica gel as the sorbent, silica to sample mass ratio of 1:1, the grinding time of 1 min. The exhaustive elution of targets was achieved by 200 µL methanol/water (9:1) containing 150 mM sodium hexane sulfonate at pH 4.5. The method validation covered linearity, recovery, precision of intraday and interday, limits of detection, limits of quantitation, and repeatability. This established method was rapid, simple, environmentally friendly, and highly sensitive.

14.
Biomed Pharmacother ; 121: 109640, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810114

RESUMO

Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to pulmonary vascular remodeling, which ultimately leads to pulmonary arterial hypertension (PAH). Osthole has been previously shown to inhibit tumor cell growth. Our previous experiments demonstrated that osthole could prevent monocrotaline-induced PAH and pulmonary artery remodeling in rats and that its effects might be associated with inhibiting PASMC proliferation. However, the exact mechanism remains unclear. In this study, we observed the inhibitory effect of osthole on platelet-derived growth factor (PDGF)-BB-induced rat PASMC growth, cell cycle progression and proliferating cell nuclear antigen (PCNA) expression, as measured by CCK-8 assay, flow cytometric analysis and western blotting, respectively. We also detected the expression and activities of the cell cycle regulators cyclin D1/CDK4, cyclin E1/CDK2, p53, p27 and p21 and the TGF-ß1/Smad/p38 signaling pathways in rat PASMCs by western blotting. Our results show that osthole effectively suppressed PDGF-BB-stimulated proliferation, PCNA protein expression, and cell cycle progression in rat PASMCs in vitro. We further demonstrated that treatment with osthole significantly induced cell cycle arrest at the G0/G1 phase in PASMCs, which was supported by the finding that osthole significantly decreased cyclin D1/CDK4 and cyclin E1/CDK2 protein levels and increased p53, p27 and p21 protein levels. These effects may partly be attributed to the downregulation of TGF-ß1/Smad/p38 signaling pathway activation. Our findings suggest that osthole is a potential therapeutic candidate that warrants further investigation regarding its potential use for the treatment of PAH.

15.
J BUON ; 24(5): 1870-1875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786849

RESUMO

PURPOSE: Berbamine is a plant-derived alkaloid with amazing and wide diversity of pharmacological properties which range from antimicrobial and anticancer. Nonetheless, the anticancer properties of Berbamine have not been thoroughly evaluated against colon cancer cells. This study was undertaken to evaluate the anticancer effects of Berbamine against human colon cancer cells (HT-29 colon cancer cells). Μethods: CCK-8 assay was used to determine the cell viability. DAPI and propidium iodide (PI) staining assays were used for the detection of apoptosis. Electron microscopy was used for the determination of autophagy. Wound healing assay was used to monitor cell migration. Protein expression was determined by western blotting. RESULTS: The results showed that Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells. DAPI and PI staining assays showed nuclear fragmentation, indicative of apoptosis in HT-29 cells. Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Electron microscopic analysis showed that Berbamine triggered the development of autophagic vesicles in the HT-29 cells which was concomitant with the increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1. Wound healing assay showed that Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells. CONCLUSION: Berbamine may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.

16.
J Immunother Cancer ; 7(1): 346, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829270

RESUMO

BACKGROUND: Inhibitors targeting VEGF and VEGFR are commonly used in the clinic, but only a subset of patients could benefit from these inhibitors and the efficacy was limited by multiple relapse mechanisms. In this work, we aimed to investigate the role of innate immune response in anti-angiogenic therapy and explore efficient therapeutic strategies to enhance efficacy of anti-angiogenic therapy against non-small cell lung cancer (NSCLC). METHODS: Three NSCLC tumor models with responses to VEGF inhibitors were designed to determine innate immune-related underpinnings of resistance to anti-angiogenic therapy. Immunofluorescence staining, fluorescence-activated cell sorting and immunoblot analysis were employed to reveal the expression of immune checkpoint regulator CD47 in refractory NSCLC. Metastatic xenograft models and VEGFR1-SIRPα fusion protein were applied to evaluate the therapeutic effect of simultaneous disruption of angiogenetic axis and CD47-SIRPα axis. RESULTS: Up-regulation of an innate immunosuppressive pathway, CD47, the ligand of the negative immune checkpoint regulator SIRPα (signal regulatory protein alpha), was observed in NSCLC tumors during anti-angiogenic therapy. Further studies revealed that CD47 upregulation in refractory lung tumor models was mediated by TNF-α/NF-κB1 signal pathway. Targeting CD47 could trigger macrophage-mediated elimination of the relapsed NSCLC cells, eliciting synergistic anti-tumor effect. Moreover, simultaneously targeting VEGF and CD47 by VEGFR1-SIRPα fusion protein induced macrophages infiltration and sensitized NSCLC to angiogenesis inhibitors and CD47 blockade. CONCLUSIONS: Our research provided evidence that CD47 blockade could sensitize NSCLC to anti-angiogenic therapy and potentiate its anti-tumor effects by enhancing macrophage infiltration and tumor cell destruction, providing novel therapeutics for NSCLC by disrupting CD47/SIRPα interaction and angiogenetic axis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31828734

RESUMO

Exosomes play an important role in cell-to-cell communication as they can transfer functional molecules such as microRNAs (miRNAs) from one cell to another, exerting biological and immunological functions. Here, we investigated the impact of HIV infection and/or heroin use on the expression of the miRNAs in plasma exosomes. We found that HIV infection or heroin use upregulated the majority (98%) of a panel of plasma exosomal miRNAs associated with immune regulation and inflammation. We also observed the enhanced effect of HIV infection and heroin use on some of these upregulated miRNAs. Our further investigation showed that the levels of four of neuro-inflammation-related miRNAs (146a, 126, 21, and let-7a) were higher in HIV-infected heroin users as compared with the control subjects. These findings indicate that the dysregulations of the plasma exosomal miRNAs support further studies to determine the role of the miRNAs in HIV and/or heroin use-mediated immune modulation and neuro-inflammation. Graphical abstract.

18.
Cancer Sci ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804030

RESUMO

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129-4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144-8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662-14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848-16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR-MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDS and could help identify those with worse-than-expected prognosis for more aggressive treatment.

19.
Nat Commun ; 10(1): 5504, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796741

RESUMO

3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.

20.
Emerg Microbes Infect ; 8(1): 367-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851879

RESUMO

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/µL, 50-99 cells/µL, 100-199 cells/µL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/µL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

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