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1.
Artigo em Inglês | MEDLINE | ID: mdl-34648632

RESUMO

BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan. OBJECTIVES: To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan. METHODS: The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression. RESULTS: The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes. CONCLUSIONS: This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression.

2.
Pathogens ; 10(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34578111

RESUMO

Healthcare workers (HCWs) are on the frontline fighting several infectious diseases including SARS-CoV-1 and COVID-19. Coronavirus neutralizing antibodies (nAbs) were recently reported to last for a certain period. The factors affecting nAbs' existence remain unclear. Here, we retrospectively analyzed the factors correlating with nAbs' from SARS-CoV-1 long-term convalescence HCWs in Taiwan. One hundred and thirty SARS-CoV-1 convalescent patients were recruited between August 2006 and March 2007. Blood samples were collected to determine the anti-nucleocapsid (N) and anti-spike (S) antibodies' existence status and neutralization ability. Neutralization ability was measured using SARS-CoV-1 pseudotyped viruses. Statistical analysis of factors associated with anti-SARS-CoV-1 antibodies' existence status was determined using SAS software. 46.2% SARS-CoV-1 convalescent patients presented anti-N antibody after three years post-infection. Among sixty participants, ten participants co-presented anti-S antibodies. Eight participants with anti-S antibody displayed neutralization ability to SARS-CoV-1. The gender, age, and disease severity of participants did not affect the anti-N antibody existence status, whereas the anti-S antibody is significantly reduced in participants with old age (>50 years, p = 0.0434) after three years post SARS-CoV-1 infection. This study suggests that age is an important factor correlated with the duration of SARS-CoV-1 protective antibody existence status.

3.
Lipids Health Dis ; 20(1): 100, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496884

RESUMO

BACKGROUND: The deleterious effect of maternal high-fat diet (HFD) on the fetal rat liver may cause later development of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effect of maternal HFD-induced maternal hepatic steatosis and dysbiosis on the fetal liver and intestines, and the effect of prenatal metformin in a rat model. METHODS: Sprague-Dawley rats were assigned to three groups (N = 6 in each group). Before mating, the rats were randomly assigned to HFD or normal-chow diet (NCD) group for 7 weeks. After mating, the HFD group rats were continued with high-fat diet during pregnancy and some of the HFD group rats were co-treated with metformin (HFMf) via drinking water during pregnancy. All maternal rats and their fetuses were sacrificed on gestational day 21. The liver and intestinal tissues of both maternal and fetal rats were analyzed. In addition, microbial deoxyribonucleic acid extracted from the maternal fecal samples was analyzed. RESULTS: HFD resulted in maternal weight gain during pregnancy, intrahepatic lipid accumulation, and change in the serum short-chain fatty acid profile, intestinal tight junctions, and dysbiosis in maternal rats. The effect of HFD on maternal rats was alleviated by prenatal metformin, which also ameliorated inflammation and apoptosis in the fetal liver and intestines. CONCLUSIONS: This study demonstrated the beneficial effects of prenatal metformin on maternal liver steatosis, focusing on the gut-liver axis. In addition, the present study indicates that prenatal metformin could ameliorate maternal HFD-induced inflammation and apoptosis in the fetal liver and intestines. This beneficial effect of in-utero exposure of metformin on fetal liver and intestines has not been reported. This study supports the use of prenatal metformin for pregnant obese women.

4.
Int J Gynecol Pathol ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347667

RESUMO

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

5.
Biomed Pharmacother ; 139: 111713, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243634

RESUMO

Galectins, are ß-galactoside binding lectins expressed in numerous cells and are known to regulate various immune responses and cellular physiological functions. Galectins have been reported to participate in the regulation of several viral infections via carbohydrate­dependent/independent manner. Galectins have displayed various regulatory functions on viral infection, however, the detailed mechanism remains unclear. More recently, some members of galectins have been reported to regulate influenza A virus (IAV) infection. In this review, we aim to analyze and summarize current findings regarding the role of galectins in IAV infection and their antiviral potential therapeutic application in the treatment of IAVs. The eligible articles were selected according to the PRISMA guidelines. Results indicate that Galectin-1(Gal-1), Galectin-3(Gal-3) and Galectin-9 (Gal-9) were found as the predominant galectins reported to participate in the regulation of IAVs infection. The inhibitory regulation of IAVs by these galectins occurred mainly through extracellular binding to glycosylated envelope proteins, further blocking the interaction between influenza envelope and sialic acid receptor, interacting with ligands or receptors on immune cells to trigger immunol or cellular response against IAVs, and endogenously interacting cellular components in the cytoplasm to activate inflammasome and autophagy. This study offers information regarding the multiple roles of galectins observed in IAVs infection and suggest that galectins has the potential to be used as therapeutic agents for IAVs.


Assuntos
Antivirais/farmacologia , Galectinas/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Infecções por Orthomyxoviridae/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos
6.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802729

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to display particular patterns of genetic diversity in the genome across geographical regions. These variations in the virus and genetic variation in human populations can determine virus transmissibility and coronavirus disease 2019 (COVID-19) severity. Genetic variations and immune differences in human populations could be the driving forces in viral evolution. Recently emerged SARS-CoV-2 variants show several mutations at the receptor binding domain in the spike (S) glycoprotein and contribute to immune escape and enhanced binding with angiotensin 1-converting enzyme 2 (ACE2). Since ACE2 and transmembrane protease serine 2 (TMPRSS2) play important roles in SARS-CoV-2 entry into the cell, genetic variation in these host entry-related proteins may be a driving force for positive selection in the SARS-CoV-2 S glycoprotein. Dendritic or liver/lymph cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin is also known to play vital roles in several pathogens. Genetic variations of these host proteins may affect the susceptibility to SARS-CoV-2. This review summarizes the latest research to describe the impacts of genetic variation in the viral S glycoprotein and critical host proteins and aims to provide better insights for understanding transmission and pathogenesis and more broadly for developing vaccine/antiviral drugs and precision medicine strategies, especially for high risk populations with genetic risk variants.


Assuntos
COVID-19/genética , COVID-19/virologia , Variação Genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/genética , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Evasão da Resposta Imune , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
7.
Risk Manag Healthc Policy ; 14: 1353-1361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833598

RESUMO

Purpose: We evaluate the association of Geriatric Nutritional Risk Index (GNRI) and the adverse outcome in elderly patients (≥65 years old) with fall injuries. Patients and Methods: Total 1071 elderly patients with fall injuries were enrolled. Patients were divided into four groups: high risk, moderate risk, low risk and no risk (GNRI: <82, 82 to <92, 92 to ≤98 and >98) for patient demography, comorbidities, and adverse outcomes analysis. Results: After 1:1 propensity score-matched analysis, 97 patients in high-risk group, 144 patients in moderate-risk group, and 114 patients in low-risk group were compared to no risk group. High-risk group patients had a 5.7-fold higher risk of mortality (p = 0.003) and prolong hospital stay (18.0 vs 12.3 days; p = 0.016) when compared to no-risk group patients. Significantly prolong hospital stay were also found in low-risk and moderate-risk group when compared to no risk group. Conclusion: A lower GNRI is associated with prolonged hospital stay in the elderly patients with fall injuries. High nutritional risk (GNRI < 82) is associated with an increased in-hospital mortality rate.

8.
Nat Microbiol ; 6(4): 435-444, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649557

RESUMO

Early events of the human immunodeficiency virus 1 (HIV-1) lifecycle, such as post-entry virus trafficking, uncoating and nuclear import, are poorly characterized because of limited understanding of virus-host interactions. Here, we used mass spectrometry-based proteomics to delineate cellular binding partners of curved HIV-1 capsid lattices and identified Sec24C as an HIV-1 host dependency factor. Gene deletion and complementation in Jurkat cells revealed that Sec24C facilitates infection and markedly enhances HIV-1 spreading infection. Downregulation of Sec24C in HeLa cells substantially reduced HIV-1 core stability and adversely affected reverse transcription, nuclear import and infectivity. Live-cell microscopy showed that Sec24C co-trafficked with HIV-1 cores in the cytoplasm during virus ingress. Biochemical assays demonstrated that Sec24C directly and specifically interacted with hexameric capsid lattices. A 2.3-Å resolution crystal structure of Sec24C228-242 in the complex with a capsid hexamer revealed that the Sec24C FG-motif bound to a pocket comprised of two adjoining capsid subunits. Combined with previous data1-4, our findings indicate that a capsid-binding FG-motif is conserved in unrelated proteins present in the cytoplasm (Sec24C), the nuclear pore (Nup153; refs. 3,4) and the nucleus (CPSF6; refs. 1,2). We propose that these virus-host interactions during HIV-1 trafficking across different cellular compartments are crucial for productive infection of target cells.


Assuntos
HIV-1/fisiologia , Proteínas de Transporte Vesicular/metabolismo , Replicação Viral , Transporte Ativo do Núcleo Celular , Motivos de Aminoácidos , Sítios de Ligação , Capsídeo/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , HIV-1/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Lentivirus de Primatas/metabolismo , Lentivirus de Primatas/fisiologia , Poro Nuclear/metabolismo , Ligação Proteica , Transcrição Reversa , Relação Estrutura-Atividade , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/genética , Integração Viral
9.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33451024

RESUMO

DC-SIGN, a C-type lectin mainly expressed in dendritic cells (DCs), has been reported to mediate several viral infections. We previously reported that DC-SIGN mediated H5N1 influenza A virus (AIVs) infection, however, the important DC-SIGN interaction with N-glycosylation sites remain unknown. This study aims to identify the optimal DC-SIGN interacting N-glycosylation sites in HA proteins of H5N1-AIVs. Results from NetNGlyc program analyzed the H5 hemagglutinin sequences of isolates during 2004-2020, revealing that seven and two conserved N-glycosylation sites were detected in HA1 and HA2 domain, respectively. A lentivirus pseudotyped A/Vietnam/1203/04 H5N1 envelope (H5N1-PVs) was generated which displayed an abundance of HA5 proteins on the virions via immuno-electron microscope observation. Further, H5N1-PVs or reverse-genetics (H5N1-RG) strains carrying a serial N-glycosylated mutation was generated by site-directed mutagenesis assay. Human recombinant DC-SIGN (rDC-SIGN) coated ELISA showed that H5N1-PVs bound to DC-SIGN, however, mutation on the N27Q, N39Q, and N181Q significantly reduced this binding (p < 0.05). Infectivity and capture assay demonstrated that N27Q and N39Q mutations significantly ameliorated DC-SIGN mediated H5N1 infection. Furthermore, combined mutations (N27Q&N39Q) significantly waned the interaction on either H5N1-PVs or -RG infection in cis and in trans (p < 0.01). This study concludes that N27 and N39 are two essential N-glycosylation contributing to DC-SIGN mediating H5N1 infection.


Assuntos
Moléculas de Adesão Celular/metabolismo , Suscetibilidade a Doenças , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Virus da Influenza A Subtipo H5N1/fisiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Substituição de Aminoácidos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H3N2 , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/ultraestrutura , Mutação , Filogenia
10.
J Clin Sleep Med ; 17(2): 325-328, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006310

RESUMO

NONE: Central sleep apnea is a rare disorder in the pediatric population with various initial presentations and is secondary to many underlying diseases. We report on a 4-year-old boy with episodes of syncope. He also had pulmonary hypertension and cardiomegaly. Polysomnography showed the finding for central sleep apnea with a high apnea-hypopnea index (up to 138.1 events/h). Brain magnetic resonance imaging showed an ill-defined area near the medulla oblongata and lower pons. The lesion from a brainstem biopsy confirmed the diagnosis of low-grade glioma. Conservative medical follow-up was suggested, and brain magnetic resonance imaging 6 months later showed no obvious tumor progression. To our best knowledge, this is the first case report that workup on the cause of syncope and pulmonary hypertension led to the final diagnosis of central sleep apnea and a brain neoplasm.


Assuntos
Glioma , Hipertensão Pulmonar , Apneia do Sono Tipo Central , Tronco Encefálico , Criança , Pré-Escolar , Humanos , Masculino , Polissonografia
11.
J Microbiol Immunol Infect ; 54(4): 596-605, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32067946

RESUMO

BACKGROUND/PURPOSE: Intentional transmission of HIV-1 is a crime. Identifying the source of transmission between HIV-1 infected cases using phylogenetic analysis has limitations, including delayed examinations after the initiation of infection and ambiguity of phyletic relationships. This study was the first to introduce phylogenetic tree Results as forensic evidence in a trial in Taiwan. METHODS: Three lawsuit cases from different district courts in Taiwan were chosen for this study. We identified the source of transmission between individuals in each lawsuit based on the maximum likelihood and Bayesian phylogenetic tree analyses using the HIV-1 sequences from molecular cloning and ultra-deep pyrosequencing (UDPS). Two gene regions of the HIV genome, env and gag, were involved. RESULTS: The results of phylogenetic analysis using sequences from molecular cloning were clear and evidential enough in lawsuits 1 and 3. Due to the delayed sampling time, the result of sequences from molecular cloning in lawsuit 2 was ambiguous. Combined with the analyzed result of sequences from UDPS and epidemiological information, the source of transmission in lawsuit 2 was further identified. CONCLUSION: Hence phylogenetic analyses cannot exclude the possibility of unsampled intermediaries, the data interpretation should be more careful and conservative, and it should not be considered as the only evidence for the source identification in a trial without epidemiological or serological information. The evaluation of the introduced UDPS method in the identification of transmission source has shown that the validity and evidential effects were still limited and need further optimization.

12.
Cancers (Basel) ; 12(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33255941

RESUMO

Accumulating evidence suggests that there is a link between the host microbiome and pancreatic carcinogenesis, and that Porphyromonas gingivalis (P. gingivalis) increases the risk of developing pancreatic cancer. The aim of the current study was to clarify the role of P. gingivalis in the pathogenesis of pancreatic cancer and the potential immune modulatory effects of probiotics. The six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice smeared P. gingivalis on the gums, causing pancreatic intraepithelial neoplasia (PanIN) after four weeks to be similar to the extent of lesions in untreated KC mice at 24 weeks. The oral inoculation of P. gingivalis of six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice caused significantly pancreatic intraepithelial neoplasia (PanIN) after treatment four weeks is similar to the extent of lesions in untreated KC mice at 24 weeks. The pancreas weights of P. gingivalis plus probiotic-treated mice were significantly lower than the mice treated with P. gingivalis alone (P = 0.0028). The histological expressions of Snail-1, ZEB-1, collagen fibers, Galectin-3, and PD-L1 staining in the pancreas were also notably lower. In addition, probiotic administration reduced the histological expression of Smad3 and phosphorylated Smad3 in P. gingivalis treated KC mice. We demonstrated that oral exposure to P. gingivalis can accelerate the development of PanIN lesions. Probiotics are likely to have a beneficial effect by reducing cancer cell proliferation and viability, inhibiting PanIN progression, and cancer cell metastasis (Epithelial-mesenchymal transition, EMT). The transforming growth factor-ß signaling pathway may be involved in the tumor suppressive effects of probiotics.

13.
Genes (Basel) ; 12(1)2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374416

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation of the S glycoprotein receptor-binding domain (RBD), and increased angiotensin 1-converting enzyme 2 (ACE2) binding and fusion, which result in an increase in SARS-CoV-2 transmissibility and infectivity. Dynamic tracking of SARS-CoV-2 showed that the D614G variant became predominant after emergence in Europe and North America, but not in China. The current absence of selective pressures from antiviral treatment suggests that the driving force for viral evolution could be variations in human population genetics. Results show that ACE2 expression is higher in Asian populations than that in European, North American, and African populations. This supports the idea that lower ACE2 expression is a driving force in the positive selection for the D614G mutation. This study suggests that the dynamics of the SARS-CoV-2 D614G mutation during the early-to-mid pandemic is associated with enhanced transmission efficiency in populations with lower ACE2 expression. Understanding the role that human genetic diversity plays in the adaptive evolution of SARS-CoV-2 may have an important impact on public health and measures to control the pandemic.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Mutação de Sentido Incorreto , Pandemias , Mutação Puntual , Receptores Virais/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , África/epidemiologia , Alelos , Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/biossíntese , Sítios de Ligação , COVID-19/etnologia , COVID-19/transmissão , COVID-19/virologia , China/epidemiologia , Grupos Étnicos/genética , Europa (Continente)/epidemiologia , Evolução Molecular , Expressão Gênica , Predisposição Genética para Doença , Variação Genética , Humanos , América do Norte/epidemiologia , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Receptores Virais/biossíntese , SARS-CoV-2/isolamento & purificação , Seleção Genética
14.
Sci Rep ; 10(1): 20319, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230218

RESUMO

Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-KrasG12D/--Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 µg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-KrasG12D/--Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient's tolerance of chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Ductal Pancreático/dietoterapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Lactobacillus , Neoplasias Pancreáticas/dietoterapia , Neoplasias Pancreáticas/tratamento farmacológico , Probióticos/administração & dosagem , Administração Oral , Animais , Carcinoma Ductal Pancreático/induzido quimicamente , Carcinoma Ductal Pancreático/microbiologia , Ceruletídeo/efeitos adversos , Desoxicitidina/administração & dosagem , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/microbiologia , Resultado do Tratamento
15.
Viruses ; 12(11)2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126529

RESUMO

Since the H7N9 avian influenza virus emerged in China in 2013, there have been five seasonal waves which have shown human infections and caused high fatality rates in infected patients. A multibasic amino acid insertion seen in the HA of current H7N9 viruses occurred through natural evolution and reassortment, and created a high pathogenicity avian influenza (HPAI) virus from the low pathogenicity avian influenza (LPAI) in 2017, and significantly increased pathogenicity in poultry, resulting in widespread HPAI H7N9 in poultry, which along with LPAI H7N9, contributed to the severe fifth seasonal wave in China. H7N9 is a novel reassorted virus from three different subtypes of influenza A viruses (IAVs) which displays a great potential threat to public health and the poultry industry. To date, no sustained human-to-human transmission has been recorded by the WHO. However, the high ability of evolutionary adaptation of H7N9 and lack of pre-existing immunity in humans heightens the pandemic potential. Changes in IAVs proteins can affect the viral transmissibility, receptor binding specificity, pathogenicity, and virulence. The multibasic amino acid insertion, mutations in hemagglutinin, deletion and mutations in neuraminidase, and mutations in PB2 contribute to different virological characteristics. This review summarized the latest research evidence to describe the impacts of viral protein changes in viral adaptation and pathogenicity of H7N9, aiming to provide better insights for developing and enhancing early warning or intervention strategies with the goal of preventing highly pathogenic IAVs circulation in live poultry, and transmission to humans.


Assuntos
Variação Genética , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Animais , Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/virologia , Aves Domésticas/virologia , Vírus Reordenados/genética , Virulência
16.
Pathogens ; 9(6)2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32485969

RESUMO

HIV-1 CRF07_BC is a B' and C subtype recombinant emerging virus and many of its viral characteristics remain unclear. Galectin-3 (Gal3) is a ß-galactose binding lectin that has been reported as a pattern recognition receptor (PRR) and is known to mediate adhesion between cells and microbes. This study aims to examine the viral characteristics of HIV-1 CRF07_BC virus and the role of extracellular galectin-3 in HIV-1 CRF07_BC infection. A total of 28 HIV-1+ injecting drug users (IDUs) were recruited and 24 (85.7%) were identified as HIV-1 CRF07_BC. Results indicate that significant higher serum galectin-3 was measured in CRF07_BC infected patients and CRF07_BC infection triggered significant galectin-3 expression (p < 0.01). Viral characteristics demonstrate that CRF07_BC virions display a higher level of envelope gp120 spikes. The virus infectivity assay demonstrated that co-treatment with galectin-3 significantly promoted CRF07_BC attachment and internalization (p < 0.01). A co-immunoprecipitation assay showed that pulldown galectin-3 co-precipitated both CD4 and gp120 proteins. Results from an enzyme-linked immunosorbent assay (ELISA) indicate that the galectin-3 promoting effect occurs through enhancement of the interaction between gp120 and CD4. This study suggests that CRF07_BC was predominant in HIV-1+ IDUs and CRF07_BC utilized extracellular galectin-3 to enhance its infectivity via stabilization of the gp120-CD4 interaction.

17.
PLoS One ; 13(12): e0202622, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521534

RESUMO

Men who have sex with men (MSM) is the major risk population of HIV-1 infection in Taiwan, and its surveillance has become critical in HIV-1 prevention. We recruited MSM subjects from 17 high-risk venues and 4 community centers in northern and southern Taiwan for anonymous HIV-1 screening during 2013-2015. Blood samples were obtained for genotyping and phylogenetic analysis, and a questionnaire survey covering demographic variables and social behavior was conducted. In total, 4,675 subjects were enrolled, yielding a HIV-1 prevalence rate of 4.3% (201/4675). Eight risk factors including subjects who did not always use condoms (OR = 1.509, p = 0.0123), those who used oil-based lubricants (OR = 1.413, p = 0.0409), and those who used recreational drugs (OR = 2.182, p = < .0001) had a higher risk of HIV-1 infection. The annual prevalence and incidence of HIV-1 showed a downward trend from 2013 to 2015 (6.56%, 5.97 per 100 person-years in 2013; 4.53%, 3.97 per 100 person-years in 2014; 1.84%, 2.08 per 100 person-years in 2015). Factors such as always using condoms, water-based lubricant use, correct knowledge of lubricating substitutes, and recreational drug use were significantly associated with the trend of incidence. Phylogenetic tree analysis showed that the cross-regional and international interaction of the local MSM population may have facilitated transmission of HIV. This survey of high-risk venues showed decreased prevalence and incidence of HIV-1 infection in Taiwan from 2013 to 2015, and this may be related to changes in behavioral patterns. Moreover, cross-regional interaction and recreational drug use need to be considered in future surveillance.


Assuntos
Infecções por HIV , HIV-1/genética , Filogenia , Minorias Sexuais e de Gênero , Adolescente , Adulto , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Infecções por HIV/transmissão , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Prevalência , Taiwan/epidemiologia
18.
PLoS One ; 12(1): e0170420, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28107423

RESUMO

The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4-47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.


Assuntos
Infecções por HIV/virologia , Adulto , Farmacorresistência Viral , Humanos , Masculino , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa
19.
Immunol Cell Biol ; 95(2): 178-188, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27559003

RESUMO

Infection and injury of the gut are associated with cell damage and release of molecules such as extracellular adenosine 5'-triphosphate (ATP), which is recognised by the purinergic P2X7 receptor (P2X7R). P2X7R is widely expressed in the gut by antigen-presenting cells (APCs) and epithelial cells, but the role of the P2X7R on epithelial cells is poorly understood. We investigated P2X7R in intestinal epithelium in vitro and in vivo using two model infections, Toxoplasma gondii and Trichinella spiralis. Lipopolysaccharide and ATP treatment of intestinal epithelial cells and infection with T. gondii in vitro did not promote inflammasome-associated interleukin-1ß (IL-1ß) or IL-18 secretion, but promoted C-C motif chemokine ligand 5 (CCL5), tumour necrosis factor-α and IL-6 production that were significantly reduced when the P2X7R was blocked. Similarly, in vivo, infection with either T. spiralis or T. gondii induced rapid upregulation of epithelial CCL5 in wild-type (wild-type (WT)) mice that was significantly reduced in P2X7R-/- littermate controls. The effects of reduced epithelial CCL5 were assayed by investigating recruitment of dendritic cells (DCs) to the epithelium. Infection induced a rapid recruitment of CD11c+CD103+ DC subsets into the epithelial layer of WT mice but not P2X7R-/- mice. In vitro chemotaxis assays and bone marrow chimeras demonstrated the importance of epithelial P2X7R in DC recruitment. P2X7R signalling in epithelial cells mediates chemokine responses to promote initiation of host immunity to infection.


Assuntos
Trato Gastrointestinal/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/parasitologia , Receptores Purinérgicos P2X7/metabolismo , Imunidade Adaptativa , Animais , Quimiocina CCL5/biossíntese , Quimiotaxia , Células Dendríticas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/parasitologia , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos C57BL , Carga Parasitária , Receptores Purinérgicos P2X7/deficiência , Linfócitos T/imunologia , Toxoplasma , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Toxoplasmose/patologia
20.
J Microbiol Immunol Infect ; 49(4): 477-86, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25442859

RESUMO

BACKGROUND: The swine-origin influenza A (H1N1) virus (S-OIV) has come to the forefront since 2009 and was identified as a new reassortant strain. The hemagglutinin (HA) glycoprotein mediates virus binding, contains antigenic regions recognized by neutralizing antibodies, and is associated with viral cross-species infection and adaption. The comparison study of codon usage preferences in influenza viral genomes was less extensive. In this study, we used codon usage pattern analyses to validate the adaption and origins of S-OIV. METHODS: Codon usage pattern was used to estimate the host adaption of S-OIVs. Phylogenetic analysis of the HA gene was conducted to understand the phylogeny of H1N1 viruses isolated from different hosts. Amino acid signature pattern on antigenic sites of HA was analyzed to understand the antigenic characteristics. RESULTS: Results of phylogenetic analyses of HA gene indicate that S-OIVs group in identical clusters. The synonymous codon usage pattern analyses indicate that the effective number of codons versus GC content at the third codon position in the HA1 gene slightly differ from those in swine H1N1 and gradually adapted to human. Our data indicate that S-OIV evolution occurred according to positive selection within these antigenic regions. A comparison of antigenic site amino acids reveals similar signature patterns between S-OIV and 1918 human influenza strains. CONCLUSION: This study proposes a new and effective way to gain a better understanding of the features of the S-OIV genome and evolutionary processes based on the codon usage pattern. It is useful to trace influenza viral origins and cross-species virus transmission.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Especificidade de Hospedeiro/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Ligação Viral , Substituição de Aminoácidos/genética , Animais , Composição de Bases/genética , Códon/genética , Genoma Viral/genética , Humanos , Filogenia , Suínos , Doenças dos Suínos/virologia
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