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1.
Liver Int ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847599

RESUMO

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

2.
J Appl Microbiol ; 135(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830802

RESUMO

AIMS: The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing annually, leading to substantial medical and health burdens. Numerous studies have demonstrated the potential effectiveness of intestinal probiotics as a treatment strategy for NAFLD. Therefore, the objective of this study is to identify a probiotic for the treatment of NAFLD. METHODS AND RESULTS: In this study, blood and fecal samples were collected from 41 healthy volunteers and 44 patients diagnosed with NAFLD. Analysis of the 16S rDNA sequencing data and quantitative real-time PCR (RT-qPCR) revealed a significant reduction in the abundance of Coprococcus in NAFLD patients. Subsequent animal experiments demonstrated that Coprococcus was able to effectively reverse liver lipid accumulation, inflammation, and fibrosis induced by a high-fat diet (HFD) in mice. CONCLUSIONS: This study provides the first in vivo evidence that Coprococcus is a beneficial bacterium capable of preventing NAFLD and has the same probiotic effect in mice as Lactobacillus GG (LGG), a positive control. Therefore, Coprococcus has the potential to serve as a probiotic for the prevention and treatment of NAFLD in humans.


Assuntos
Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Probióticos , Animais , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Dieta Hiperlipídica/efeitos adversos , Probióticos/farmacologia , Probióticos/uso terapêutico , Camundongos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fezes/microbiologia , Fezes/química , Adulto , Feminino , Fígado/metabolismo , Microbioma Gastrointestinal , Pessoa de Meia-Idade , Modelos Animais de Doenças
3.
BMC Health Serv Res ; 22(1): 1564, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36544158

RESUMO

BACKGROUND: Coronavirus-2019 pandemic in China aroused increasing interest in telemedicine-supported glycaemic control. We hypothesize that age might influence usage and efficacy of telemedicine-supported glycaemic control. This study aims to measure the effects of a doctor-nurse-patient Mobile Health Management System (MHMS) for fasting plasma glucose (FPG) control in patients with type 2 diabetes mellitus (T2DM). METHODS: Four hundred sixty four patients with T2DM were recruited. A one-hour diabetes education provided to each patient and subsequent follow-ups arranged in the 1st, 2nd, 4th, 8th, and 12th week after enrollment were recorded in MHMS. The effectiveness of MHMS was defined as the proportion of patients achieving FPG target (below 126 mg/dL or 7.0mml/L). RESULTS: Among the enrolled 464 patients (age: 55.0 ± 13.7 years) who were divided into three groups: young (18-40 years), middle-aged (41-65 years) and elderly (> 65 years), 424 ones completed all follow-ups of 12 weeks. FPG decreased from 178.38 ± 95.04 to 117.90 ± 14.22 mg/dL in the young group, from 180.00 ± 91.08 to 122.94 ± 37.95 mg/dL in the middle-aged group, and from 174.24 ± 80.64 to 128.88 ± 23.4 mg/dL in the elderly group. The proportion of FPG-target-achieved patients increased from 46.2 to 90.4% in the young group, from 32.6 to 82.8% in the middle-aged group, and from 29.5 to 73.3% in the elderly group. The proportion of FPG-target-achieved patients between three age groups were statistically significant (P < 0.001). And the changes of proportion of FPG-target-achieved patients at different follow-up times were statistically significant (P = 0.037). Compared with the young group, the elderly group achieved poorer FPG level (P = 0.032). CONCLUSION: MHMS can help patients with T2DM lower FPG and improve proportion of FPG-target-achieved patients. Younger patients may achieve better glycaemic control than older patients. MHMS may serve multitudinous patients with T2DM to achieve adequate FPG self-management.


Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Pessoa de Meia-Idade , Humanos , Adulto , Diabetes Mellitus Tipo 2/terapia , Glicemia , Estudos Prospectivos , População do Leste Asiático , China , Jejum
4.
J Cell Mol Med ; 25(8): 4073-4087, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33689215

RESUMO

Persistent hepatic damage and chronic inflammation in liver activate the quiescent hepatic stellate cells (HSCs) and cause hepatic fibrosis (HF). Several microRNAs regulate the activation and proliferation of HSCs, thereby playing a critical role in HF progression. Previous studies have reported that miR-188-5p is dysregulated during the process of HF. However, the role of miR-188-5p in HF remains unclear. This study investigated the potential role of miR-188-5p in HSCs and HF. Firstly, we validated the miR-188-5p expression in primary cells isolated from liver of carbon tetrachloride (CCl4 )-induced mice, TGF-ß1-induced LX-2 cells, livers from 6-month high-fat diet (HFD)-induced rat and 4-month HFD-induced mice NASH models, and human non-alcoholic fatty liver disease (NAFLD) patients. Furthermore, we used miR-188-5p inhibitors to investigate the therapeutic effects of miR-188-5p inhibition in the HFD + CCl4 induced in vivo model and the potential role of miR-188-5p in the activation and proliferation of HSCs. This present study reported that miR-188-5p expression is significantly increased in the human NAFLD, HSCs isolated from liver of CCl4 induced mice, and in vitro and in vivo models of HF. Mimicking the miR-188-5p resulted in the up-regulation of HSC activation and proliferation by directly targeting the phosphatase and tensin homolog (PTEN). Moreover, inhibition of miR-188-5p reduced the activation and proliferation markers of HSCs through PTEN/AKT pathway. Additionally, in vivo inhibition of miR-188-5p suppressed the HF parameters, pro-fibrotic and pro-inflammatory genes, and fibrosis. Collectively, our results uncover the pro-fibrotic role of miR-188-5p. Furthermore, we demonstrated that miR-188-5p inhibition decreases the severity of HF by reducing the activation and proliferation of HSCs through PTEN/AKT pathway.


Assuntos
Células Estreladas do Fígado/citologia , Cirrose Hepática/prevenção & controle , MicroRNAs/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos
5.
Biochem Cell Biol ; 99(5): 617-628, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33831322

RESUMO

Autophagy dysfunction is a hallmark of type 1 diabetes. However, the precise molecular mechanism of proteinuria-induced dysfunctional autophagy remains unclear. Herein, we investigated the role of programmed cell death 4 (PDCD4) in the regulation of autophagy in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro. RT-qPCR, immunohistochemistry (IHC), and western blotting demonstrated an upregulation of Pdcd4 mRNA and protein in streptozotocin (STZ)-induced DKD rats, as compared to the control. In addition, IHC and western blotting of a unilateral ureteral obstruction mouse model showed an upregulation of PDCD4 in the disease group, as compared to their respective controls. IHC analysis of kidney biopsy samples of human DKD patients showed an upregulation of PDCD4 compared to the control. Western blotting of the STZ-induced DKD rat tissues displayed a low microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, as compared to the control. It was found that albumin overload in cultured PTECs upregulated the expression of PDCD4 and p62 and decreased the expression of LC3-II and autophagy-related 5 (Atg5) proteins. The knockout of Pdcd4 in cultured PTECs could reduce albumin-induced dysfunctional autophagy, as evidenced by the recovery of Atg5 and LC3-II protein. The forced expression of PDCD4 could further suppress the expression of the crucial autophagy-related gene Atg5. Evidence suggests that endogenous PDCD4 promotes proteinuria-induced dysfunctional autophagy by negatively regulating Atg5. Therefore, PDCD4 may be a potential therapeutic target in DKD.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Túbulos Renais Proximais/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adulto , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/genética , Autofagia , Proteína 5 Relacionada à Autofagia/genética , Bovinos , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteinúria/metabolismo , Proteínas de Ligação a RNA/genética , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/metabolismo , Estreptozocina
6.
J Cell Physiol ; 234(2): 1758-1767, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30146678

RESUMO

Atherosclerosis is widely known to be a chronic inflammatory disease. C-reactive protein (CRP), an important inflammatory factor, plays an essential role in the pathogenesis of atherosclerosis. Nicotine, the main addictive component of cigarette, has been shown to induce the production of CRP. The aim of this study was to investigate the effect of rosmarinic acid (RA), a polyphenol with antiinflammatory activity, on nicotine-induced elevation of CRP in vascular smooth muscle cells (VSMCs). We found that pretreatment of VSMCs with RA attenuated nicotine-induced expression of CRP in a time- and dose-dependant manner. In addition, RA also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and reactive oxygen species (ROS) production resulting from nicotine treatment in VSMCs. To confirm these findings in vivo, we constructed a nicotine-induced atherosclerosis rat model. RA did not significantly reduce the serum nicotine level of the rats, whereas it significantly decreased the levels of serum lipids, including concentrations of cholesterol, triglycerides, and low-density lipoprotein cholesterol, and the serum level of CRP. RA also led to diminished nicotine-induced activation of NLRP3 inflammasome and elevation in the CRP level in the aortic tissue of the model rats. The results of this study suggested a protective role of RA in nicotine-induced atherosclerosis by inhibiting the ROS-NLRP3 inflammasome-CRP axial, and RA therefore represented a potential effective therapeutic approach to atherosclerosis, in particular for those who smoke.


Assuntos
Anti-Inflamatórios/farmacologia , Aterosclerose/prevenção & controle , Proteína C-Reativa/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamação/prevenção & controle , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Nicotina , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/imunologia , Aterosclerose/metabolismo , Proteína C-Reativa/imunologia , Células Cultivadas , Modelos Animais de Doenças , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/metabolismo , Lipídeos/sangue , Masculino , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ácido Rosmarínico
7.
J Am Chem Soc ; 141(50): 19524-19528, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31789023

RESUMO

Synthesizing tubes of large diameters is important for materials science and nanotechnology but remains a largely unsolved challenge. We report herein an approach to program the width of DNA helical tubes by controlling the rigidity and curvature of repeating units via single-stranded bricks strategy. The rigidity of repeating units can be controlled by its thickness, and the curvature can be tuned by double-helical twist density. A single-step annealing allows for the fabrication of helical tubes with defined chirality and widths ranging from ∼50 to ∼550 nm.


Assuntos
DNA/química , Nanotubos/química , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
8.
Clin Immunol ; 175: 56-68, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27940139

RESUMO

Autophagy is involved in both innate and adaptive immune regulation. We propose that autophagy regulates activation of TLR3 in macrophages and is thereby essential for development of pristane-induced arthritis. We found that pristane treatment induced autophagy in macrophages in vitro and in vivo, in spleen cells from pristane injected rats. The induced autophagy was associated with STAT1 phosphorylation and expression of IRF1 and TLR3. Blocking the pristane activated autophagy by Wortmannin and Bafilomycin A1 or by RNAi of Becn1 led to a downregulation of the associated STAT1-IRF1-TLR3 pathway. Most importantly, the development of arthritis was alleviated by suppressing either autophagy or TLR3. We conclude that pristane enhanced autophagy, leading to a STAT1-IRF1 controlled upregulation of TLR3 expression in macrophages, is a pathogenic mechanism in the development of arthritis.


Assuntos
Artrite Experimental/tratamento farmacológico , Autofagia/efeitos dos fármacos , Fator Regulador 1 de Interferon/metabolismo , Macrófagos/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Terpenos/farmacologia , Receptor 3 Toll-Like/metabolismo , Animais , Artrite Experimental/metabolismo , Regulação para Baixo/efeitos dos fármacos , Macrófagos/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
9.
Hepatology ; 64(1): 58-72, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26663205

RESUMO

UNLABELLED: Cholesterol metabolism disorder in hepatocytes predicts a higher risk of metabolic syndrome (MetS). Long noncoding RNAs (lncRNAs) have emerged as critical players in cellular cholesterol metabolism, but their functions are not systematically clarified. Here, we have identified a novel lncRNA named lnc-HC negatively regulating cholesterol metabolism within hepatocytes through physical interaction with hnRNPA2B1. By further binding to the target messenger RNA of Cyp7a1 or Abca1, the lnc-HC-hnRNPA2B1 complex decreases expressions of the two genes that are implicated in cellular cholesterol excretion. lnc-HC knockdown can strongly recover the cholesterol disorder in vivo. In the upstream pathway, lnc-HC is up-regulated by high cholesterol by the transcription activator, CCAAT/enhancer-binding protein beta. CONCLUSION: These findings suggest a subtle feed-forward regulation of lnc-HC in cholesterol metabolism and define a novel line of evidence by which lncRNAs modulate the metabolic system at the post-transcriptional level. (Hepatology 2016;64:58-72).


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol/metabolismo , Hepatócitos/enzimologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica , Humanos , Fígado/metabolismo , Camundongos , Distribuição Aleatória , Ratos
10.
BMC Cancer ; 15: 461, 2015 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-26055874

RESUMO

BACKGROUND: Mounting evidence suggests that miRNAs have major functions in tumor pathogenesis, and this study aimed to identify the candidate miRNA and investigate its role in nasopharyngeal carcinoma (NPC). METHODS: MiRNA and mRNA expressions were screened by microarray assays. The cell proliferation, colony formation and migration ability were measured by MTT, soft agar and wound healing assays, respectively. The tumor growth suppression was evaluated by xenografting in nude mice. The plasma miR-223 levels in NPC patients were detected by TaqMan analysis. Real-time quantitative PCR and Western blotting were used to confirm miR-223 and MAFB expression levels. The targeting relationship between miR-223 and MAFB was verified using dual luciferase reporter assay. RESULTS: The miR-223 expression was decreased in CNE-1, CNE-2 cells as compared with NP69 cells, an immortalized human nasopharyngeal epithelial cell line, and its level also reduced in NPC patients' plasma as compared with healthy controls. Exogenous expression of miR-223 in CNE-2 cells could inhibit cell proliferation both in vitro and in vivo. Extrogenous miR-223 in CNE-2 cells would decrease the ability of colony formation and migration. MAFB, a transcription factor of Maf family members, was identified as a target gene of miR-223. We found that migration and invasion abilities were inhibited by MAFB silencing. CONCLUSIONS: MiR-223 negatively regulates the growth and migration of NPC cells via reducing MAFB expression, and this finding provides a novel insight into understanding miR-223 regulation mechanism in nasopharyngeal carcinoma tumorigenesis.


Assuntos
Proliferação de Células/genética , Fator de Transcrição MafB/biossíntese , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Animais , Carcinogênese , Carcinoma , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Transcrição MafB/antagonistas & inibidores , Fator de Transcrição MafB/genética , Camundongos , MicroRNAs/biossíntese , MicroRNAs/sangue , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , RNA Mensageiro/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Mol Cell Biochem ; 398(1-2): 95-104, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25217205

RESUMO

Excessive reactive oxygen species (ROS) generation has been implicated as one of main agents in ouabain-induced anticancer effect. Unfortunately, the signaling pathways under it are not very clarified. In the present study, we investigated the molecular mechanism involved in ouabain-induced ROS generation and cell apoptosis on human U373MG and U87MG glioma cells. Ouabain-induced glioblastoma cells apoptosis and increased ROS generation. Clearance ROS by three different ROS scavenger partly, but not totally, reversed ouabain's effect on cell apoptosis. Ouabain-induced ROS generation was not regulated by calcium overload, reduced nicotinamide adenine dinucleotide phosphate oxidation, but by p66Shc phosphorylation. Ouabain treatment increased p66Shc Ser36 phosphorylation. Knockdown of p66Shc by siRNA significantly inhibited ROS generations in response to ouabain. Ouabain-induced p66Shc phosphorylation through Src/Ras/extracellular signal-regulated kinase signal pathway. Our results uncovered a novel signaling pathway with p66Shc, ouabain-induced ROS generation, and glioblastoma cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ouabaína/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Western Blotting , Cálcio/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Fosforilação/efeitos dos fármacos , Interferência de RNA , Proteínas Adaptadoras da Sinalização Shc/genética , Transdução de Sinais/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Fatores de Tempo , Proteínas ras/metabolismo , Quinases da Família src/metabolismo
12.
Clin Infect Dis ; 59(1): e1-9, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24723287

RESUMO

BACKGROUND: Studies on the transmission of human immunodeficiency virus (HIV) and sexually transmitted diseases in female sex workers (FSWs) have been limited primarily to inferences drawn by focusing on defined geographical areas. METHODS AND FINDINGS: This serial cross-sectional study was conducted in mainland China from 2008 through 2012. Data for 827 079 participants was analyzed. We classified venues such as karaoke bars and hotels as high tier and venues such as hair salons and barbershops, massage parlors, and other public outdoor venues as low tier based on the participants' socioeconomic status. FSWs who worked at the venues and those who were present on the days of the survey were recruited. The prevalence of HIV decreased from 0.6% in 2008 to 0.3% in 2012, the syphilis prevalence ranged from 2.4% to 3.2% between 2008 and 2012, and hepatitis C virus (HCV) prevalence decreased from 0.9% in 2008 to 0.8% in 2012. Further, we found that HIV, syphilis, and HCV prevalence proportions were high in FSWs from low tiers. CONCLUSIONS: HIV, syphilis, and HCV prevalence among FSWs in our study decreased during the study period. Comprehensive intervention strategies, particularly those that focus on low-tier and older FSWs, are needed in order to decrease the disease burden in this population.


Assuntos
Epidemias , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Profissionais do Sexo , Sífilis/epidemiologia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Transmissão de Doença Infecciosa , Feminino , Infecções por HIV/transmissão , Hepatite C/transmissão , Humanos , Pessoa de Meia-Idade , Prevalência , Sífilis/transmissão , Adulto Jovem
13.
J Immunol ; 188(7): 3506-12, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22387551

RESUMO

Protein arginine methyltransferases (PRMTs), catalyzing methylation of both histones and other cellular proteins, have emerged as key regulators of various cellular processes. This study aimed to identify key PRMTs involved in Ag-induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of PRMT1 in the IL-4-induced eosinophil infiltration process. E3 rats were i.p. sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The expressions of PRMT1-6, eotaxin-1, and CCR3 in lungs were screened by real-time quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT inhibitor) and small interfering RNA-PRMT1 were used to interrupt the function of PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI rats to observe the effects on inflammatory parameters. The results showed that PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI-1 and the knockdown of PRMT1 expression were able to downregulate the expressions of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells. Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary inflammation, reduce IL-4 production and humoral immune response, and abrogate eosinophil infiltration into the lungs. In summary, PRMT1 expression is upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of PRMT1 activity can abrogate IL-4-dependent eotaxin-1 production to influence the pulmonary inflammation with eosinophil infiltration. The findings may provide experimental evidence that PRMT1 plays an important role in asthma pathogenesis.


Assuntos
Antígenos/toxicidade , Quimiocina CCL11/biossíntese , Células Epiteliais/metabolismo , Interleucina-4/farmacologia , Proteína-Arginina N-Metiltransferases/fisiologia , Eosinofilia Pulmonar/imunologia , Animais , Asma/metabolismo , Quimiocina CCL11/genética , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Naftalenossulfonatos/farmacologia , Naftalenossulfonatos/uso terapêutico , Ovalbumina/toxicidade , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/biossíntese , Proteína-Arginina N-Metiltransferases/genética , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/tratamento farmacológico , Eosinofilia Pulmonar/enzimologia , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Ratos , Proteínas Recombinantes/farmacologia , Sistema Respiratório/citologia , Organismos Livres de Patógenos Específicos , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/uso terapêutico
14.
Zhonghua Yu Fang Yi Xue Za Zhi ; 48(10): 857-61, 2014 Oct.
Artigo em Zh | MEDLINE | ID: mdl-25573122

RESUMO

OBJECTIVE: To explore the prevalence of syphilis and HSV-2 among female sex workers (FSWs) who use new types of drugs in Jiaozhou city. METHODS: Through convenient sampling, an anonymous questionnaire survey was conducted among female sex workers to collect demographic characteristics, new-type drugs abusing characteristics and related sexual behaviors from October to December, 2013. Blood specimens were drawn for serological tests of syphilis antibody and HSV-2 antibody. Urine specimens of the subjects surveyed were collected to test for methamphetamine. Differences in demographic characteristics, new-type drug abusing characteristics, and sexual behaviours between drug-abusing FSWs and non-drug-abusing FSWs were compared by t-test and χ(2)-test. RESULTS: A total of 460 FSWs were recruited in this study, and 105 FSWs admitted their drug abuse history. Among the 341 urine specimens confirmed to be methamphetamine positive, there were 3 FSWs claimed that they never abuse new-type drugs. The rate of new-type drug abuse was 23.5% (108/460). A total of 71.4% (75/105) of the new drug-abusing FSWs started using drugs under 25 years old. The main reasons for drug abuse were clients request (24, 22.9%), making more money (23, 21.9%) and companion temptations (22, 21.0%). Totally, 41.9% of them (44/105) took drugs with 4-5 persons, 32.4% (34/105) had sex with 2-3 men after taking drugs, and 60.2% of new-type drug-abusing FSWs (65/108) used condoms in the latest commercial intercourse, while only 7.4% FSWs (8/108) used condoms every time during their commercial sex activities in the recent month. Compared with FSWs having no drug abuse behavior, drug-abusing FSWs had higher single proportion (73.2% (79/108) vs 63.6% (224/352), χ(2) = 8.64, P < 0.05), lower condom use rate in the recent month (7.4% (8/108) vs 22.7% (80/352), χ(2) = 12.53, P < 0.01) and higher pregnancy rate in the recent 6 months (24.1% (26/108) vs 8.8% (31/352), χ(2) = 17.74, P < 0.01) and most of them come from the middle and high-level entertainmens (78.7% (85/108) vs 65.1% (229/352), χ(2) = 13.09, P < 0.01). Among the new-type drug-abusing FSWs, the prevalence rates of syphilis and HSV-2 were 12.0% (13/108) and 55.6% (60/108) , respectively. A total of 33 FSWs claimed that they were diagnosed with STDs in the recent year (30.6%) . The rates of syphilis(12.0% (13/108) vs 4.0% (14/352), χ(2) = 9.72, P < 0.01), HSV-2(55.6% (60/108) vs 39.2% (138/352), χ(2) = 9.01, P < 0.01) and diagnosed STDs (30.6% (33/108) vs 17.9% (63/352), χ(2) = 8.02, P < 0.01) among the drug-abusing FSWs were significantly higher than those of non-drug-abusing FSWs. CONCLUSION: There is a higher proportion of new-type drug abuse among the FSWs in Jiaozhou, with significantly higher prevalence rates of syphilis and HSV-2 infection, compared with non-new types of drug abusing FSWs. Prevalent risk sexual behaviors and ignorance of new-types drugs' harm were seen among them.


Assuntos
Drogas Desenhadas , Herpes Genital/epidemiologia , Assunção de Riscos , Profissionais do Sexo/estatística & dados numéricos , Comportamento Sexual/efeitos dos fármacos , Comportamento Sexual/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias , Sífilis/epidemiologia , China/epidemiologia , Preservativos , Feminino , Herpesvirus Humano 2 , Humanos , Metanfetamina , Gravidez , Prevalência , Fatores de Risco , Trabalho Sexual , Parceiros Sexuais
15.
China CDC Wkly ; 6(1): 6-11, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38223658

RESUMO

Introduction: Human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) clinics play a critical role in identifying and diagnosing HIV cases. This study aimed to describe the trend of HIV positivity rate (HPR) among Chinese VCT clinics between 2015 and 2022. Methods: This study utilized data from the China Information System for Disease Control and Prevention to analyze the trend in the HPR for VCT clinics from 2015 to 2022. The HPR was calculated by dividing the number of newly-reported HIV cases by the number of HIV tests, multiplied by 100%. To identify temporal and spatial trends in the HPR, we employed joinpoint regression analysis and the Getis-Ord hotspot analysis. Results: From 2015 to 2022, VCT clinics in China performed a total of 22,075,386 HIV tests, leading to the identification of 260,353 HIV cases, resulting in a HPR of 1.18%. The HPR consistently declined over the study period, with an average annual percent change (AAPC) of -7.5% (95% confidence interval: -12.6%, -2.2%, P<0.05). The number of HPR hotspots also decreased from 41 in 2015 to 23 in 2022. These HPR hotspots were primarily located in Yunnan, Sichuan, Guangdong, and Guangxi provincial-level administrative divisions (PLADs). Among the 31 PLADs, 16 showed a significant decrease in HPR during the study period (AAPC<0, PAAPC<0.05). Conclusions: VCT clinics in China have played a significant role in identifying HIV cases. The declining HPR observed in these clinics may indicates the progress has been made in some degree in mitigating HIV among high-risk populations. Therefore, it is crucial to further improving the utilization of VCT clinics for HIV testing.

16.
Emerg Microbes Infect ; 13(1): 2352426, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38713582

RESUMO

Linking identified MPOX cases to care is essential for MPOX control. This study aims to investigate the intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men (MSM) in China. A cross-sectional online survey was conducted in early August 2023 in China. Respondents were recruited by community-based organizations (CBOs), collecting information on demographics, health status, behavioural and psychological characteristics. Univariate and multivariate logistic regression analyses were performed to examine the predictors of intentions to seek healthcare and self-isolate for MPOX within the MSM population. A total of 7725 participants were recruited, with a median age of 30 years. 92.21% of the participants would seek healthcare for MPOX-like symptoms, but only 52.50% intended to self-isolate if diagnosed. Intentions to seek healthcare were lower among those with MPOX-like symptoms in the past 3 months (standardized prevalence ratio (SPRs) = 0.82, 95% CI: 0.74-0.89) and the willingness to self-isolate was reduced among those diagnosed with MPOX in the past 3 months (SPRs = 0.65, 95% CI: 0.48-0.87). Participants free of sexually transmitted infections (STIs) and those aware of their HIV status were more likely to seek healthcare and self-isolate than those with STIs or unaware of their HIV status. Regular followers of MPOX information and those perceiving a low risk of infection were more inclined to take preventive measures. These findings highlight the need for targeted MPOX prevention strategies for high-risk groups and the importance of addressing barriers in infectious disease prevention response.


Assuntos
Homossexualidade Masculina , Intenção , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Masculino , Estudos Transversais , China , Adulto , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto Jovem , Pessoa de Meia-Idade , Infecções Sexualmente Transmissíveis/prevenção & controle , Inquéritos e Questionários , Adolescente , Minorias Sexuais e de Gênero/psicologia
17.
Front Public Health ; 12: 1369931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476479

RESUMO

Background: Men who have sex with men (MSM) have a high prevalence of HIV and a low rate of HIV testing in China. HIV self-testing (HIVST) presents a viable strategy for expanding HIV testing among MSM. However, the impact of HIVST on risk behaviors among MSM remains controversial. Our study sought to ascertain this impact. Methods: From April 2021 to January 2022, a mixed-methods study was conducted in Qingdao City, employing both quantitative and qualitative methodologies. The quantitative component entailed a cohort study among MSM who had used HIVST. Generalized estimating equations fitting Poisson regressions were used to analyze the changes in risk behaviors of MSM in short time after HIVST (ST-HIVST) and longer time after HIVST (LT-HIVST) compared to before HIVST. Subsequently, we conducted in-depth interviews with 18 MSM who completed the follow-up to delve deeper into the impact of HIVST on MSM. Results: A total of 410 MSM were recruited in the cohort, of whom 83 were lost to follow-up. Compared to before HIVST, there were no significant changes in risk behaviors in ST-HIVST (p > 0.05), while the proportion of recreational drugs abuse (20.7% vs. 33.3%), commercial sex (14.6% vs. 22.9%), and unprotected anal sex (95.9% vs. 98.5%) increased significantly in LT-HIVST (p < 0.05). Specific changes varied across demographic characteristics. According to qualitative interviews, MSM might have decreased risk perception and increased risk behaviors after HIVST. Conclusion: The use of HIVST may promote MSM to engage in risk behaviors. In the future, customized HIVST promotion programs need to be developed to expand HIV testing among MSM and simultaneously control their risk behaviors.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , HIV , Autoteste , Estudos de Coortes , Trabalho Sexual , Autocuidado/métodos , Infecções por HIV/epidemiologia , Teste de HIV , Assunção de Riscos
18.
Front Public Health ; 12: 1364913, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651127

RESUMO

Background: The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs. Methods: A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage. Results: A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%). Conclusion: The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Profilaxia Pós-Exposição , Assunção de Riscos , Humanos , Masculino , China , Homossexualidade Masculina/estatística & dados numéricos , Adulto , Infecções por HIV/prevenção & controle , Profilaxia Pós-Exposição/estatística & dados numéricos , Estudos Retrospectivos , Inquéritos e Questionários , Estudos de Coortes , Adulto Jovem , Pessoa de Meia-Idade
19.
Sci Rep ; 13(1): 554, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631515

RESUMO

Human immunodeficiency virus (HIV) sexual transmission among men who have sex with men (MSM) has increased markedly in Beijing, China in the past decade. Pre-exposure prophylaxis (PrEP) is a highly efficacious biomedical prevention strategy that remarkably reduces HIV-transmission risk. This study examined PrEP awareness among MSM and the factors influencing it. From April to July 2021, respondent-driven sampling was used to conduct a cross-sectional survey among MSM in Beijing, China. Demographic, behavior, and awareness data regarding PrEP were collected. The factors influencing PrEP awareness were assessed using univariate and multivariable logistic regression. In total, 608 eligible responders were included in the study. Among the respondents, 27.9% had PrEP awareness, 3.3% had taken PrEP, and 57.9% expressed interest in receiving PrEP, if required. Greater odds of PrEP awareness were associated with higher education level (adjusted odds ratio [aOR] 3.525, 95% confidence interval [CI] 2.013-6.173, P < 0.0001), greater HIV-related knowledge (aOR 3.605, 95% CI 2.229-5.829, P < 0.0001), HIV testing (aOR 2.647, 95% CI 1.463-4.788, P = 0.0013), and sexually transmitted infections (aOR 2.064, 95% CI 1.189-3.584, P = 0.0101). Lower odds of PrEP awareness were associated with higher stigma score (aOR 0.729, 95% CI 0.591-0.897, P = 0.0029). The findings indicate sub-optimal awareness and low utilization of PrEP in Beijing and highlight PrEP inequities among MSM with stigma. Strengthening the training of peer educators in disseminating PrEP knowledge and reducing stigma are critical for improving PrEP awareness.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Pequim/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , HIV , Estudos Transversais , China/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde
20.
China CDC Wkly ; 5(13): 283-286, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37139144

RESUMO

What is already known about this topic?: Research evidence is insufficient to suggest whether routine human immunodeficiency virus (HIV) screening in healthcare settings is effective in promoting greater awareness of HIV-positive status. What is added by this report?: This study found that, following the implementation of routine HIV screening in hospitals in Xishuangbanna Prefecture, Yunnan Province, there was a significant increase in the number of HIV screenings, positive results, and the positive rate of HIV screening in primary-level hospitals. What are the implications for public health practice?: Routine hospital-based HIV screening is effective in identifying HIV infections in areas with concentrated epidemics.

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