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1.
Nanomaterials (Basel) ; 11(10)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34685101

RESUMO

Accurate and reliable non-contact temperature sensors are imperative for industrial production and scientific research. Here, Er3+/Tm3+/Yb3+ co-doped NaYF4 phosphors were studied as an optical thermometry material. The typical hydrothermal method was used to synthesize hexagonal Er3+/Tm3+/Yb3+ co-doped NaYF4 phosphors and the morphology was approximately rod-like. The up-conversion emissions of the samples were located at 475, 520, 550, 650, 692 and 800 nm. Thermo-responsive emissions from the samples were monitored to evaluate the relative sensing sensitivity. The thermal coupled energy level- and non-thermal coupled energy level-based luminescence intensity ratio thermometry of the sample demonstrated that these two methods can be used to test temperature. Two green emissions (520 and 550 nm), radiated from 2H11/2/4S3/2 levels, were monitored, and the maximum relative sensing sensitivities reached to 0.013 K-1 at 297 K. The emissions located in the first biological window (650, 692 and 800 nm) were monitored and the maximum relative sensing sensitivities reached to 0.027 (R692/650) and 0.028 K-1 (R692/800) at 297 K, respectively. These results indicate that Er3+/Tm3+/Yb3+ co-doped NaYF4 phosphors have potential applications for temperature determination in the visible and the first biological window ranges.

2.
Allergy Asthma Immunol Res ; 13(5): 684-696, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34486255

RESUMO

Arachidonic acid 15-lipoxygenase (ALOX15) is an enzyme that can oxidize polyunsaturated fatty acids. ALOX15 is strongly expressed in airway epithelial cells, where it catalyzes the conversion of arachidonic acid to 15-hydroxyeicosatetraenoic acid (15-HETE) involved in various airway inflammatory diseases. Interleukin (IL)-4 and IL-13 induce ALOX15 expression by activating Jak2 and Tyk2 kinases as well as signal transducers and activators of transcription (STATs) 1/3/5/6. ALOX15 up-regulation and subsequent association with phosphatidylethanolamine-binding protein 1 (PEBP1) activate the mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway, thus inducing eosinophil-mediated airway inflammation. In addition, ALOX15 plays a significant role in promoting the migration of immune cells, such as immature dendritic cells, activated T cells, and mast cells, and airway remodeling, including goblet cell differentiation. Genome-wide association studies have revealed multiple ALOX15 variants and their significant correlation with the risk of developing airway diseases. The epigenetic modifications of the ALOX15 gene, such as DNA methylation and histone modifications, have been shown to closely relate with airway inflammation. This review summarizes the role of ALOX15 in different phenotypes of asthma, chronic obstructive pulmonary disease, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyps, suggesting new treatment strategies for these airway inflammatory diseases with complex etiology and poor treatment response.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34465138

RESUMO

URFs are more likely developed among HIV-1 infections through MSM because of multiple subtypes co-circulation. In this study, two novel URFs deriving from two HIV-positive subjects (HB010014, HB010063) were identified in Shijiazhuang, Hebei province, China, and two sequences formed a distinct monophyletic cluster. The further recombination analysis showed that of two new URFs were consisted of CRF01_AE and CRF07_BC. The subregion phylogenetic analysis indicated that CRF01_AE segments were traced back to cluster 4 of CRF01_AE strains, which were prevalent among HIV-1 infections through MSM in China. New URFs being developing gradually and spreading released that more and more novel recombinant strains of HIV-1 could be developed, which means that the past prevention strategies need to be adjusted.

4.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
5.
Sci Rep ; 11(1): 15761, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344927

RESUMO

Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-ß/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-ß/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.

6.
Rev Med Virol ; 31(4): e2195, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260780

RESUMO

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , COVID-19/patologia , Citocinas/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Leucócitos/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia
7.
Front Microbiol ; 12: 662573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079529

RESUMO

Human endogenous retroviruses (HERVs) make up ~8% of the human genome, and for millions of years, they have been subject to strict biological regulation. Many HERVs do not participate in normal physiological activities in the body. However, in some pathological conditions, they can be abnormally activated. For example, HIV infection can cause abnormal activation of HERVs, and under different infection conditions, HERV expression may be different. We observed significant differences in HERV-K transcription levels among HIV-1 subtype-infected individuals. The transcriptional levels in the HERV-K gag region were significantly increased in HIV-1 B subtype-infected patients, while the transcriptional levels in the HERV-K pol region were significantly increased in CRF01_AE and CRF07_BC subtype-infected patients. In vitro, the transcriptional levels of HEVR-K were increased 5-fold and 15-fold in MT2 cells transfected with two different HIV-1 strains (B and CRF01_AE, respectively). However, there was no significant difference in transcriptional levels among regions of HERV-K. When MT2 cells were infected with different subtypes of HIV-1 Tat proteins (B, CRF01_AE), which is constructed by lentiviruses, and the transcription levels of HERV-K were increased 4-fold and 2-fold, respectively. Thus, different subtypes of HIV-1 have different effects on HERV-K transcription levels, which may be caused by many factors, not only Tat protein.

8.
Clin Toxicol (Phila) ; : 1-8, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34080498

RESUMO

OBJECTIVES: Overdose with paracetamol modified-release (MR) formulation, a bilayer tablet containing 69% slow-release component, has been increasing since its introduction to the market. However, little evidence exists for the management of MR paracetamol overdose. We aimed to develop a population pharmacokinetic (PK) model for immediate-release (IR) and MR paracetamol and its major metabolism, and quantitatively understand the formulation difference in toxicity assessment based on the nomogram line. METHODS: Data from a cross-over study design in nine healthy volunteers administered a single supratherapeutic oral dose (80 mg/kg) of either IR and MR paracetamol were available from a published study. Plasma concentrations for paracetamol and its metabolites glucuronide (APAPG) and sulfate conjugate (APAPS) for both formulations were measured and analysed with population pharmacokinetic (PK) method using NONMEM. Toxicity in both formulations was assessed by comparing the simulated paracetamol concentrations under different paracetamol dose levels with the 150 mg/L nomograms. The difference in the assessment was compared between the two formulations. RESULTS: Paracetamol concentrations for the IR formulation were described with a two-compartment model with first-order input and a lag time. The delayed time-course of MR paracetamol concentrations was best captured by a parallel absorption model in which the slow-release component was a serial zero-order then the first-order process. The formation of APAPG was linear, while APAPS concentrations were best fitted by a Michaelis-Menten process. The relative bioavailability of MR paracetamol compared to IR (FMR/IR) was estimated as 0.81. The simulated probability of making different toxicity assessments based on nomogram line was increased with dose levels and was as high as 14.6% after 22 g IR or MR paracetamol ingested. CONCLUSIONS: A joint parent-metabolite model to describe time-course profiles of both IR and MR paracetamol and its metabolites APAPG and APAPS concentrations was developed. Simulations from the model showed that toxicity assessment based on the 150 mg/L nomograms is not suitable in MR paracetamol overdoses.

9.
Int Arch Allergy Immunol ; : 1-12, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34148047

RESUMO

BACKGROUND: Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP. OBJECTIVE: We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP. METHODS: Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of BNC1, TP63, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes. RESULTS: BNC1 mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, p = 0.0003) and control groups (2.40-fold, p < 0.0001). BNC1 staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of BNC1 mRNA was strongly correlated with TP63 mRNA level both in tissue biopsies (r = 0.78, p < 0.0001) and epithelial scrapings (r = 0.97, p < 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in TH2 inflammation (IL33, CCL26, CLC, and ALOX15). CONCLUSIONS: Overexpression of BNC1 may be associated with increased expression of TP63, and possibly contribute to the epithelial barrier defects and TH2 inflammation in CRSwNP.

10.
J Infect ; 83(1): 76-83, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932447

RESUMO

OBJECTIVES: Shenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China. METHODS: Plasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses. RESULTS: 10,378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster. CONCLUSIONS: The prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Farmacorresistência Viral/genética , Genes pol , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia
11.
J Steroid Biochem Mol Biol ; 211: 105907, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33965570

RESUMO

The H9N2 avian influenza viruses infect poultry worldwide, and can potentially cause a human pandemic without adaptation. Vitamin D3 (D3) is increasingly being recognized for its extra-skeletal roles, such as the inflammatory and immune responses to infection. The aim of this study was to analyze the changes in vitamin D metabolizing enzymes and vitamin D receptor (VDR) in the lung tissues of mice infected with H9N2. The mice were intranasally inoculated with the appropriate dose of the virus, and various clinical indices were measured on days 3, 7, 14 and 21 post-infection. H9N2 infection significantly increased the expression levels of 1α-hydroxylase mRNA and protein, which is the activating enzyme of 25-hydroxyvitamin D (25(OH)D3), but had no significant effect on the 25(OH)D3 inactivating enzyme 24-hydroxylase, indicating that inactive D3 might be converted to its active form in the H9N2-infected lungs. Furthermore, a significant increase was also observed in the VDR mRNA and protein levels, suggesting enhanced responsiveness of the lung tissues to 1, 25(OH)2D3 post H9N2 infection. In addition, daily 25(OH)D3 injection from day 2-14 post-infection did not affect the clinical signs, virus replication and cytokine (IL-1ß and TNF-α) production in the lungs of the infected mice. Given that the biological effects of D3 rely on its activation, and the binding of 1, 25(OH)2D3 to VDR in specific tissues, our findings provide novel insights into the possible role of vitamin D in the development and progression of influenza.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Pulmão/virologia , Infecções por Orthomyxoviridae/complicações , Receptores de Calcitriol/metabolismo , Infecções Respiratórias/virologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Animais , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Receptores de Calcitriol/genética , Infecções Respiratórias/metabolismo , Infecções Respiratórias/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33926207

RESUMO

Homosexual contact is one of the main transmission routes of HIV-1 epidemic in Hebei, China. Several subtypes of HIV are prevalent simultaneously in the population, which always lead to the emergency of unique recombinant forms (URFs). In this study, we reported two new URFs from two HIV-1 positive subjects infected through homosexual contact route in Hebei, China. Phylogenetic and recombinant analyses based on the near full-length genome of the two URFs both revealed the two URFs are the second generation of recombinant strains originated from CRF01_AE and CRF07_BC. The CRF01_AE segments of two URFs located in cluster 4 of CRF01_AE strains in the phylogenetic tree. The emergence of the novel CRF01_AE/CRF07_BC recombinant forms with complicated genomic structures indicated the importance of the continuous monitoring of the HIV-1 epidemic and new URFs among the men who have sex with men populations.

13.
Entropy (Basel) ; 23(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917645

RESUMO

The integrated energy system (IES) is an efficient method for improving the utilization of renewable energy. This paper proposes an IES based on fuel, wind and solar energies, following an optimization study focused on determining optimal device capacities. The study included gas turbines, wind turbines, solar photovoltaic panels, ground source heat pumps, absorption chillers/heaters, batteries, and thermal storage. Objectives were incorporated into the optimization model for the overall performance of the IES; these included the primary energy saving rate, annual cost-saving rate, and carbon dioxide emission reduction. Then, the nondominated sorting genetic algorithm II was employed to solve the optimization problem for multiple objectives. Ultimately, the verification and sensitivity analyses of the optimization method were achieved by a case study of hospital buildings in Harbin. The optimization results indicated a primary energy saving rate, annual cost saving rate, and carbon dioxide emission reduction rate of 17.3%, 39.8%, and 53.8%, respectively. The total installed capacity for renewable energy generation accounted for 64.5% of performance optimization. Moreover, the price of natural gas affected the economic indicators of the IES-but failed to impact energy consumption indicators.

14.
PLoS Genet ; 17(3): e1009413, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33684136

RESUMO

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.


Assuntos
Predisposição Genética para Doença , Variação Genética , Cardiopatias Congênitas/genética , Padrões de Herança , Adulto , Alelos , Cardiomiopatia Hipertrófica Familiar/genética , Mapeamento Cromossômico , Feminino , Genótipo , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único , Medição de Risco , Adulto Jovem
15.
Infect Immun ; 89(6)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33722928

RESUMO

H9N2 avian influenza virus has been continuously circulating among poultry and can infect mammals, indicating that this virus is a potential pandemic strain. During influenza pandemics, secondary bacterial (particularly pneumococcal) pneumonia usually contributes to excessive mortality. In the present study, we observed the dynamic effect of H9N2 virus infection on host defense against secondary pneumococcal infection in mice. BALB/c mice were intranasally inoculated with 1.2 × 105 PFU of H9N2 virus followed by 1 × 106 CFU of Streptococcus pneumoniae at 7, 14, or 28 days post-H9N2 infection (dpi). The bacterial load, histopathology, body weight, and survival were assessed after pneumococcal infection. Our results showed that H9N2 virus infection had no significant impact on host resistance to secondary pneumococcal infection at 7 dpi. However, H9N2 virus infection increased pulmonary pneumococcal clearance and reduced pneumococcal pneumonia-induced morbidity after secondary pneumococcal infection at 14 or 28 dpi, as reflected by significantly decreased bacterial loads, markedly alleviated pulmonary histopathological changes, and significantly reduced weight loss in mice infected with H9N2 virus followed by S. pneumoniae compared with mice infected only with S. pneumoniae Further, the significantly decreased bacterial loads were observed when mice were previously infected with a high dose (1.2 × 106 PFU) of H9N2 virus. Also, similar to the results obtained in BALB/c mice, improvement in pulmonary pneumococcal clearance was observed in C57BL/6 mice. Overall, our results showed that pulmonary pneumococcal clearance is improved after resolution of H9N2 virus infection in mice.


Assuntos
Coinfecção , Vírus da Influenza A Subtipo H9N2/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/imunologia , Animais , Carga Bacteriana , Modelos Animais de Doenças , Camundongos , Fatores de Tempo
16.
AIDS Res Hum Retroviruses ; 37(9): 694-705, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33390081

RESUMO

HIV recombination contributes greatly to its diversity and produces many circulating recombinant forms (CRFs) and unique recombinant forms (URFs). In China, 24 CRFs have been reported to date, and CRFs cause more than 80% of HIV infections. However, the prevalence of CRFs might still be underestimated, as a high level of onward transmission of URFs has been reported. In this study, we analyzed all Chinese pol region (2,253-3,252) sequences in the HIV Database to evaluate potential new CRFs in China. HIV-1 genotypes were verified by the Context-based Modeling for Expeditious Typing (COMET) tool. Maximum-likelihood (ML) trees were constructed based on sequences with unassigned genotypes. Cluster Picker 1.2.1 was used to identify transmission clusters. Meanwhile, a jumping-profile hidden Markov model (jpHMM) was used to perform recombination breakpoint analysis. Beast 1.7.5 was used to estimate the time of the most recent common ancestor of new CRFs. In the HIV databases, CRF01_AE was the most prevalent genetic form in China, accounting for 39.69% of all national infections, followed by CRF07_BC (20.47%), subtype B (17.50%), CRF08_BC (6.60%), subtype C (6.28%), CRF55_01B (2.06%), and other CRFs (1.77%). The URFs were responsible for 5.31% of all infections nationwide. Among URFs, genomes comprising BC, 01BC, 01B, and 01C were dominant. Finally, 17 potential CRFs and 1 novel CRF were identified. BEAST analysis indicates that novel CRF originated around in 2009. The data highlight that more CRFs have been spreading in China. HIV-1 pol sequences that are commonly used to explore drug resistance are helpful for the surveillance of epidemics of different HIV-1 genotypes.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia
17.
J Pharmacokinet Pharmacodyn ; 48(1): 69-82, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32996046

RESUMO

Cellular response to insults may result in the initiation of different cell death processes. For many cases the cell death process will result in an acute release of cellular material that in some circumstances provides valuable information about the process (i.e. may represent a biomarker). The characteristics of the biomarker release is often informative and plays critical roles in clinical practice and toxicology research. The aim of this study is to develop a general, semi-mechanistic model to describe cell turnover and biomarker release by injured tissue that can be used for estimation in pharmacokinetic and (toxicokinetic)-pharmacodynamic studies. The model included three components: (1) natural tissue turnover, (2) biomarker release from cell death and its movement from the cell through the tissue into the blood, (3) different target insult mechanisms of cell death. We applied the general model to biomarker release profiles for four different cell insult causes. Our model simulations showed good agreements with reported data under both delayed release and rapid release cases. Additionally, we illustrate the use of the model to provide different biomarker profiles. We also provided details on interpreting parameters and their values for other researchers to customize its use. In conclusion, our general model provides a basic structure to study the kinetic behaviour of biomarker release and disposition after cellular insult.

18.
Microb Pathog ; 150: 104645, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33285220

RESUMO

Influenza virus is responsible for significant morbidity and mortality worldwide. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the major cause of death in influenza virus infected patients. Recent studies indicated that active glucagon like peptide-1 (GLP-1) encoded by glucagon (GCG) gene exerts anti-inflammatory functions. The aim of this study was to determine the potential role of active GLP-1 in H9N2 influenza virus-induced ALI/ARDS in mice. First, we uncovered that GCG mRNA expression levels and GCG precursor protein levels were significantly increased, but total GLP-1 and active GLP-1 levels were decreased in the lungs of H9N2-infected mice. Next, liraglutide, an active GLP-1 analogue, was used to treat infected mice and to observe its effects on H9N2 virus-induced ALI. Liraglutide treatment ameliorated the declined body weight, decreased food intake and mortality observed in infected mice. It also alleviated the severity of lung injury, including lowering lung index, decreasing inflammatory cell infiltration and lowing total protein levels in bronchoalveolar lavage fluid (BALF). In addition, liraglutide did not influence viral titers in infected lungs, but decreased the levels of interleukin-1ß, interleukin-6 and tumor necrosis factor-α in BALF. These results indicated that liraglutide alleviated H9N2 virus-induced ALI in mice most likely due to lower levels of pro-inflammatory cytokines.


Assuntos
Lesão Pulmonar Aguda , Vírus da Influenza A Subtipo H9N2 , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar , Peptídeo 1 Semelhante ao Glucagon , Humanos , Liraglutida/farmacologia , Pulmão , Camundongos
19.
Artigo em Inglês | MEDLINE | ID: mdl-33287627

RESUMO

Isolation and culture of human immunodeficiency virus (HIV) are an important basis for acquired immune deficiency syndrome (AIDS) etiology, immunology, drug screening, clinical treatment, and vaccine research. CRF01_AE is one of the predominant strains of HIV-1 in China. However, there are few HIV-1 CRF01_AE isolates that have been reported. In this study, 16 HIV-1 CRF01_AE strains from Guangxi, China, were isolated, and the near full-length genomes were reverse transcribed and amplified in two halves with the 1 kb overlapping region. The polymerase chain reaction products were sequenced directly. The phylogenetic analysis results showed that all of the 16 isolated strains were CRF01_AE recombinant form, and two clusters were set up in the phylogenetic tree. The tropic prediction of 16 strains showed that 2 isolates were CCR5 tropic, and the others are CXCR4 tropic. Eight of the isolated strains are drug resistant according to the genetic prediction. These 16 near full-length characterized CRF01_AE isolates obtained in this study will provide valuable genomic and phenotypic information on HIV-1 strains circulating in China for related researches.

20.
Br J Clin Pharmacol ; 87(5): 2392-2396, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33179287

RESUMO

Paracetamol-induced hepatotoxicity is the leading cause of acute liver failure in many countries, including North America and the United Kingdom. Among the three dominant paracetamol metabolism pathways (i.e. glucuronidation, sulfation and oxidation), the importance of sulfation is often underestimated because of the general thinking that the sulfation pathway is saturated at therapeutic doses and ultimately accounts for a limited proportion of the fate of a paracetamol dose. We illustrate that insufficient sulfation leads to a shift in biotransformation of paracetamol to toxic oxidation pathways and patients with low sulfate reserves are at higher risk of paracetamol toxicity. Here, we propose that sulfation is of critical importance in understanding the risk of liver toxicity secondary to paracetamol overdose. Serum inorganic sulfate, a measurable substrate on the causal path of paracetamol-induced liver toxicity, should be considered a biomarker for potential toxicity as well as a target for treatment.

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