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1.
Commun Biol ; 7(1): 545, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714724

RESUMO

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.


Assuntos
Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas , RNA Circular , Fatores de Transcrição SOX9 , Neoplasias Gástricas , Fator de Transcrição 4 , beta Catenina , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Humanos , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOX9/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , beta Catenina/metabolismo , beta Catenina/genética , RNA Circular/genética , RNA Circular/metabolismo , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Nus , Masculino , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade
2.
Chem Commun (Camb) ; 60(7): 862-865, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38131618

RESUMO

One-pot synthesis of structurally diverse sulfurized/selenated 4-aminopyrimidines has been reported via t-BuOK/K2S2O8-promoted four-component reaction of mixed nitriles and disulfides/diselenides. Mechanistic studies indicate that the reaction proceeds through radical and ionic pathways, and an alkenyl sulfide serves as a key intermediate.

3.
Front Public Health ; 11: 1117897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026354

RESUMO

Objectives: This study aimed to investigate the prevalence and related factors of abdominal obesity among urban adults aged 35 to 79 years in southwest China. Methods: From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,981 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. Abdominal obesity was defined as waist circumference ≥ 90 cm for men and ≥ 85 cm for women. Results: The prevalence of abdominal obesity was 30.7%, 24.8% in males and 33.9% in females (p < 0.001). The prevalence of abdominal obesity increased with BMI. The prevalence of abdominal obesity was positively correlated with age, sex, marriage, alcohol consumption, hypertension and diabetes, and negatively correlated with high education level, smoking and Physical activity. Conclusion: The prevalence of abdominal obesity among adults aged 35-79 in urban communities in southwest China is high, which is close to that of adults in urban communities in China. We should strengthen health education among the population, adopt healthy diet, maintain moderate physical activity and other measures to curb the prevalence of abdominal obesity in urban communities in southwest China.


Assuntos
Obesidade Abdominal , Obesidade , Masculino , Adulto , Humanos , Feminino , Obesidade Abdominal/epidemiologia , Fatores de Risco , Prevalência , Obesidade/epidemiologia , China/epidemiologia
4.
Nat Commun ; 14(1): 7413, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973806

RESUMO

Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P < 0.001). Both OS and DFS in the ICG group are significantly better than that in the non-ICG group (log-rank P = 0.015; log-rank P = 0.012, respectively). There is a difference in the overall recurrence rates between the ICG and non-ICG groups (17.8% vs 31.0%). Compared with conventional lymphadenectomy, ICG guided laparoscopic lymphadenectomy is safe and effective in prolonging survival among patients with resectable GC.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Verde de Indocianina , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Laparoscopia/métodos , Imagem Óptica/métodos
5.
iScience ; 26(8): 107450, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37583552

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a severe threat to the health of pigs globally. Host factors play a critical role in PRRSV replication. Using PRRSV as a model for genome-scale CRISPR knockout (KO) screening, we identified a host factor critical to PRRSV infection: sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Our findings show that SMPDL3B restricted PRRSV attachment, entry, replication, and secretion and that its depletion significantly inhibited PRRSV proliferation, indicating that SMPDL3B plays a positive role in PRRSV replication. Our data also show that SMPDL3B deficiency resulted in an accumulation of intracellular lipid droplets (LDs). The expression level of key genes (ACC, SCD-1, and FASN) involved in lipogenesis was increased, whereas the fundamental lipolysis gene, ATGL, was inhibited when SMPDL3B was knocked down. Overall, our findings suggest that SMPDL3B deficiency can effectively inhibit viral infection through the modulation of lipid metabolism.

6.
Int J Ophthalmol ; 16(7): 1145-1154, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465496

RESUMO

AIM: To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor (VEGF) drugs in the treatment of macular edema (ME) due to retinal vein occlusion (RVO) based on the evidence pooled from current clinical trials and observational studies. METHODS: A systematic literature search was conducted on nine online databases from inception until April 30, 2022. The main endpoints were best corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events (AEs). Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs. The retrieved data were analyzed using Stata software (version 12.0). RESULTS: A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis. It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo [weight mean difference (WMD)=-0.03, P=0.001; WMD=-0.05, P=0.019], but the effects were not different from that of ranibizumab at 6mo. Moreover, there was not statistically significant difference in the proportion of patients gaining ≥15 letters at 12-24mo between aflibercept and ranibizumab [odds ratio (OR)=1.16, P=0.427]. Conbercept had higher mean CMT change effects at 1mo (WMD=-14.43, P=0.014) and 6mo (WMD=-35.63, P≤0.001) compared with ranibizumab. Meanwhile, the mean CMT change effects at 1mo (WMD=-10.14, P=0.170), 6mo (WMD=-26.98, P=0.140) and 12-24mo (WMD=-12.34, P=0.071) were comparable among the groups. Similarly, AEs were not significantly different among the treatments (OR=0.75, P=0.305; OR=1.04, P=0.89). The stability of effect size of mean BCVA and CMT improved with the increase in sample size. Aflibercept and conbercept required fewer injections compared with ranibizumab. CONCLUSION: This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept, ranibizumab, and aflibercept in the treatment of RVO-ME. Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab. Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

8.
Vaccine ; 41(14): 2387-2396, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36872144

RESUMO

Pasteurella multocida (P. multocida) infection frequently results in porcine atrophic rhinitis and swine plague, leading to large economic losses for the swine industry worldwide. P. multocida toxin (PMT, 146 kDa) is a highly virulent key virulence factor that plays a vital role in causing lung and turbinate lesions. This study developed a multi-epitope recombinant antigen of PMT (rPMT) that showed excellent immunogenicity and protection in a mouse model. Using bioinformatics to analyse the dominant epitopes of PMT, we constructed and synthesized rPMT containing 10 B-cell epitopes, 8 peptides with multiple B-cell epitopes and 13 T-cell epitopes of PMT and a rpmt gene (1,974 bp) with multiple epitopes. The rPMT protein (97 kDa) was soluble and contained a GST tag protein. Immunization of mice with rPMT stimulated significantly elevated serum IgG titres and splenocyte proliferation, and serum IFN-γ and IL-12 were upregulated by 5-fold and 1.6-fold, respectively, but IL-4 was not. Furthermore, the rPMT immunization group exhibited alleviated lung tissue lesions and a significantly decreased degree of neutrophil infiltration compared with the control groups post-challenge. In the rPMT vaccination group, 57.1% (8/14) of the mice survived the challenge, similar to the bacterin HN06 group, while all the mice in the control groups succumbed to the challenge. Thus, rPMT could be a suitable candidate antigen for developing a subunit vaccine against toxigenic P. multocida infection.


Assuntos
Infecções por Pasteurella , Pasteurella multocida , Animais , Camundongos , Suínos , Pasteurella multocida/genética , Epitopos de Linfócito B/genética , Proteínas de Bactérias/genética , Infecções por Pasteurella/prevenção & controle , Vacinação , Imunização
9.
Front Microbiol ; 14: 1087484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36819040

RESUMO

Introduction: Pseudorabies virus (PRV) is the pathogenic virus of porcine pseudorabies (PR), belonging to the Herpesviridae family. PRV has a wide range of hosts and in recent years has also been reported to infect humans. N6-methyladenosine (m6A) modification is the major pathway of RNA post-transcriptional modification. Whether m6A modification participates in the regulation of PRV replication is unknown. Methods: Here, we investigated that the m6A modification was abundant in the PRV transcripts and PRV infection affected the epitranscriptome of host cells. Knockdown of cellular m6A methyltransferases METTL3 and METTL14 and the specific binding proteins YTHDF2 and YTHDF3 inhibited PRV replication, while silencing of demethylase ALKBH5 promoted PRV output. The overexpression of METTL14 induced more efficient virus proliferation in PRV-infected PK15 cells. Inhibition of m6A modification by 3-deazaadenosine (3-DAA), a m6A modification inhibitor, could significantly reduce viral replication. Results and Discussion: Taken together, m6A modification played a positive role in the regulation of PRV replication and gene expression. Our research revealed m6A modification sites in PRV transcripts and determined that m6A modification dynamically mediated the interaction between PRV and host.

10.
Front Public Health ; 10: 865870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504973

RESUMO

Objective: The aim of our study was to assess the prevalence and geographic variation of obesity-related hypertension in China among adults aged 45 years or older. Methods: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Stratified sample households covered 150 counties/districts and 450 villages/urban communities from 28 provinces by using household questionnaires, clinical measurements, and blood-based bioassays. A multivariable non-conditional logistic regression model was used to analyze the risk factors correlated with obesity-related hypertension. Results: The prevalence of obesity-related hypertension was 22.7%, ~120 million people, among adults aged 45 years or older in China. For people in the age ranges of 45-54, 55-64, 65-74, and ≥75 years, the prevalence of obesity-related hypertension was 16.7, 24.3, 27, and 26.7%, respectively, and the prevalence of obesity-related hypertension among hypertensive participants was 66.0, 60.9, 54.2, and 47.3%, respectively. Compared with non-obesity-related hypertension, the obesity-related hypertensive patients had a higher prevalence of diabetes mellitus, dyslipidemia, and hyperuricemia (all P < 0.0001). The prevalence of obesity-related hypertension showed a decreasing gradient from north to south and from east to west. Multivariate logistic regression analysis showed that female gender, living in urban areas, diabetes mellitus, dyslipidemia, and hyperuricemia were positively correlated with obesity-related hypertension. Conclusion: The prevalence of obesity-related hypertension among adults aged 45 years or older was high in China. Among hypertensive participants, older age was negatively correlated with obesity-related hypertension. Obesity-related hypertensive participants are more prone to aggregation of risk factors of atherosclerotic cardiovascular disease.


Assuntos
Hipertensão , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Estudos Longitudinais , Hipertensão/epidemiologia , Prevalência , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco
11.
J Org Chem ; 87(24): 16851-16859, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36416373

RESUMO

We report herein the Pd-catalyzed selective ring-opening reaction of cyclopropenones with vinyl epoxides. By using a commercially available Pd2(dba)3·CHCl3-BINAP catalyst, a wide range of conjugated alkadienyl carboxylates could be accessed in good yield and excellent regioselectivity. The new application of zwitterionic π-allyl palladium intermediates has been demonstrated in organic synthesis.

12.
Ophthalmic Res ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36412621

RESUMO

INTRODUCTION: To assess changes of choroidal thickness (ChT) after administration of 1% atropine for 1 week in myopia, emmetropia, and hyperopia children. METHODS: A total of 235 children aged 4-8 years, which included 46 myopia, 34 emmetropia, and 155 hyperopia patients were recruited and divided into three groups according to the spherical equivalent with the use of 1% atropine twice a day for 1 week. The ChT was measured at baseline and 1 week. RESULTS: In the myopia and emmetropia groups, following administration of 1% atropine gel, the ChT thickened significantly under the fovea (i.e., from 278.29 ± 53.01 µm to 308.24 ± 57.3 µm, P < 0.05; from 336.10 ± 78.60 µm to 353.46 ± 70.22 µm, P < 0.05, respectively) and at all intervals from the fovea, while in the hyperopia group, there was no significant difference in the ChT except the nasal side (P < 0.05) . CONCLUSION: Topical administration of 1% atropine gel for 1 week significantly increased the subfoveal and parafoveal ChT in children with myopia and emmetropia. Atropine did not increase the ChT in hyperopia children, except at the nasal side.

13.
Front Cell Infect Microbiol ; 12: 866410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573790

RESUMO

Dental caries severely hinders efficient access to adequate energy in wildlife. Different food supplies will develop characteristic plaque, and the microorganisms of these plaque are closely related to dental health. Here, plaque samples from panda cubs with caries and caries-free were collected for 16S rRNA high-throughput sequencing. All sequences clustered into 337 operational taxonomic units (OTUs; 97% identity), representing 268 independent species belonging to 189 genera, 98 families, 51 orders, 24 classes, and 13 phyla. Two groups shared 218 OTUs, indicating the presence of a core plaque microbiome. α diversity analysis showed that the microbial diversity in plaques with caries exceeded that of caries-free. The dominant phyla of plaque microbiota included Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Actinobacteria. The dominant genera included unclassified Neisseriaceae, Actinobacillus, Lautropia, Neisseria, Porhyromonas, unclassified Pasteurellaceae, Moraxella, Streptococcus, Bergeywlla and Capnocytophaga. ß diversity analysis showed that the plaque microbial community structure was different between two groups. Using LEfSe analysis, 19 differentially abundant taxa were identified as potential biomarkers. Finally, function predictions analysis showed All the energy related metabolic pathways on KEGG level 2 were enriched in caries-active group. Consistent with the mainstream caries-causing narrative, our results illuminate the lack of information regarding the oral microflora composition and function within giant panda cubs.


Assuntos
Cárie Dentária , Microbiota , Ursidae , Animais , Bactérias/genética , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética , Ursidae/genética
14.
Microb Drug Resist ; 28(6): 660-669, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35639423

RESUMO

Objective: The main objective was to assess the correlation between antibiotic use and carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Escherichia coli (CREC) induction by antibiotics. Materials and Methods: A retrospective cohort study was conducted from January 2017 to December 2020. This study included patients with K. pneumoniae and E. coli. Kaplan-Meier analysis and Cox proportional hazard model were used to estimate the hazard of carbapenem-resistant Enterobacterales (CRE), whereas restricted cubic spline regression was used to visualize the hazard of CRE by antibiotics at different doses. Results: Two thousand fifty-six K. pneumoniae patients and 3,243 E. coli patients were included. After Cox proportional hazard model analysis, carbapenems or 1st-cephalospoins or penicillin monotherapy, male and ICU admission were associated with CRKP. CREC was associated with quinolone monotherapy. Time-to-event analysis indicated that carbapenem, ß-lactamase inhibitor mixtures, and quinolones were associated with higher 30-day CRKP hazards than other antibiotics (χ2 = 33.670, p < 0.001). Further restricted cubic spline regression analysis found that the hazard of CRKP induction decreased with the increased dose of ß-lactamase inhibitor mixtures, but there was no significant change in the hazard ratio of CRKP induction with the increased dose of quinolones. Moreover, there was an obvious characteristic of "parabolic curve" for the hazard of CREC induction due to ß-lactamase inhibitor mixtures, and the hazard value gradually increased with the dose, reached the maximum at 24 g, and finally gradually decreased from 26 g. Conclusions: Rational use of antibiotics should be implemented and antimicrobial stewardship policies should be adjusted according to the characteristics of each hospital.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Escherichia coli , Infecções por Klebsiella , Quinolonas , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , China , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Estudos Retrospectivos , Inibidores de beta-Lactamases/farmacologia
15.
Ophthalmic Res ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35500560

RESUMO

INTRODUCTION: Myopia is an increasingly serious health problem in China. The aim of this study was to investigate the prevalence of myopia and the factors associated with it among students in Nantong, China, to show the current status of myopia prevention. METHODS: This school-based, cross-sectional study examined students from all high schools in an urban area of Nantong, China. At least two classes were randomly selected from each grade of each school. A self-reported questionnaire was used to collect the required information.Univariate analyses were performed to identify associations between myopia and various parameters.Non-cycloplegic autorefraction and visual acuity were assessed for each student. Factors that were statistically significant in univariate analyses were selected for multivariate analyses. Myopia was defined as a spherical equivalent refraction of ≤ -0.5 diopters. RESULTS: The completion percentage of students out of the whole high school was 6.5%.The overall prevalence of myopia was 94%. The response percentage of the number of validated questionnaires was 90.2%, of which 50.2% (n = 1,466) were from male participants, and 49.8% (n = 1,452) were from female participants. The mean (SD) of age was 15.22±1.75 years, ranging from 12-18 years. Factors such as female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia (P < 0.05). In the myopic population, most students (67.9%) did not take measures to prevent further progression of myopia. CONCLUSION: The prevalence of myopia among high school students was 94%. Female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia. Most students with myopia (67.9%) did not take measures to prevent further progression of myopia.

16.
Chem Commun (Camb) ; 58(45): 6550-6553, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35582920

RESUMO

An (NH4)2S2O8-promoted cross-coupling of thiols/diselenides and sulfoxides to construct unsymmetrical disulfides/selenosulfides is disclosed. Control experiments demonstrate that (NH4)2S2O8 acts as an acid and an oxidant, while both ionic and radical routes are involved in the reaction. The KIE experiments reveal that C-H bond cleavage of sulfoxides was involved in the turnover-limiting step.


Assuntos
Dissulfetos , Compostos de Sulfidrila , Dissulfetos/química , Compostos de Sulfidrila/química , Sulfóxidos
17.
Front Microbiol ; 13: 839698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401490

RESUMO

The management of perioperative antibiotic options after lung transplantation varies widely around the world, but there is a common trend to limit antibiotic use duration. Metagenomic next-generation sequencing (mNGS) has become a hot spot in clinical pathogen detection due to its precise, rapid, and wide detection spectrum of pathogens. Thus, we defined a new antibiotic regimen adjustment strategy in the very early stage (within 7 days) after lung transplantation mainly depending on mNGS reports combined with clinical conditions to reduce the use of antibiotics. To verify the clinical effect of the strategy, we carried out this research. Thirty patients who underwent lung transplantation were finally included, whose information including etiology, antibiotic adjustment, and the effect of our strategy was recorded. Lung transplant recipients in this study were prescribed with initial antibiotic regimen immediately after surgery; their antibiotic regimens were adjusted according to the strategy. According to our study, the entire effectiveness of the strategy was 90.0% (27/30). Besides, a total of 86 samples containing donor lung tissue, recipient lung tissue, and bronchoalveolar lavage fluid (BALF) were obtained in this study; they were all sent to mNGS test, while BALF was also sent to pathogen culture. Their results showed that the positive rate of BALF samples was higher (86.67%) than that of donor's lung tissue (20.0%) or recipient's lung tissue (13.33%) by mNGS test, indicating BALF samples are more valuable than other clinical samples from early postoperative period to guide the early adjustment of antibiotics after lung transplantation. It is effective for mNGS combined with traditional methods and clinical situations to optimize antibiotic regimens in lung transplantation recipients within 7 days after surgery.

18.
Theranostics ; 12(4): 1904-1920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198079

RESUMO

Background: Efforts to prevent recurrence in gastric cancer (GC) patients are limited by current incomplete understanding of the pathological mechanisms. The present study aimed to identify novel tumour metastasis-associated genes and investigate potential value of these genes in clinical diagnosis and therapy. Methods: RNA sequencing was performed to identify differentially expressed genes related to GC metastasis. The expression and prognostic significance of fatty acid binding protein 4 (FABP4) were evaluated in two independent cohorts of GC patients. Chromatin immunoprecipitation sequencing, diverse mouse models and assays for transposase-accessible chromatin with high-throughput sequencing were used to investigate the roles and mechanisms of action of FABP4. Results: The results of the present multicentre study confirmed an association between a decrease in the expression of FABP4 and poor outcomes in GC patients. FABP4 inhibited GC metastasis but did not influence tumour growth in vitro and in vivo. Mechanistically, FABP4 binding with peroxisome proliferator-activated receptor γ (PPAR-γ) facilitated the translocation of PPAR-γ to the nucleus. FABP4 depletion suppressed PPAR-γ-mediated transcription of cell adhesion molecule 3 (CADM3), which preferentially governed GC metastasis. Notably, the PPAR-γ agonist rosiglitazone reversed the metastatic properties of FABP4-deficient GC cells in vitro and demonstrated viable therapeutic potential in multiple mouse models. For GC patients with diabetes, low FABP4 portends better prognosis than high FABP4 after receipt of rosiglitazone treatment. Additionally, chromatin inaccessibility induced by HDAC1 reduced FABP4 expression at the epigenetic level. Conclusions: Our findings suggest that chromatin inaccessibility orchestrates a reduction in FABP4 expression, which inhibits CADM3 transcription via PPAR-γ, thereby resulting in GC metastasis. The antidiabetic drug rosiglitazone restores PPAR-γ/CADM3 activation in FABP4-deficient GC and thus has promising therapeutic potential.


Assuntos
Neoplasias Gástricas , Tiazolidinedionas , Animais , Cromatina , Modelos Animais de Doenças , Proteínas de Ligação a Ácido Graxo/genética , Humanos , Hipoglicemiantes/farmacologia , Camundongos , PPAR gama/metabolismo , Rosiglitazona/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Tiazolidinedionas/uso terapêutico
19.
BMC Cardiovasc Disord ; 22(1): 2, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991490

RESUMO

INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.


Assuntos
Hipertensão/complicações , Hiperuricemia/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Ácido Úrico/sangue , Idoso , China/epidemiologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hiperuricemia/sangue , Hiperuricemia/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais
20.
J Asian Nat Prod Res ; 24(1): 66-75, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33550877

RESUMO

Eighteen novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, and mp. Due to the steric hindrance, the substituents on the C = N double bond of all hydrazine compounds (except E/Z = 4/1 for IV-1g, IV-1l, IV-2b, and E/Z = 3/2 for IV-1n, IV-3a) adopted E configuration. Among all compounds, four compounds 2, 4, IV-1j, and IV-1n exhibited potent nematicidal activity than their precursor paeonol, especially 5-nitropaeonol (2) and 3,5-dinitropaeonol (4) displayed the most potent nematicidal activity Heterodera glycines in vivo with LC50 values of 32.3307 and 36.7074 mg/L, respectively.


Assuntos
Hidrazonas , Tylenchoidea , Animais , Antinematódeos , Hidrazonas/farmacologia , Estrutura Molecular
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