RESUMEN
HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.
Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Infecciones por VIH/epidemiología , Genotipo , China/epidemiología , FilogeniaRESUMEN
Overlap syndrome is the combination of autoimmune liver diseases, and this term usually describes the coexistence of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in the same patient. Membranous nephropathy (MN) is the most common pattern of idiopathic nephrotic syndrome in patients without diabetes. The coexistence of PBC-AIH overlap syndrome and MN is very rare. Herein, the patient we describe exhibited large amounts of proteinuria and hepatic dysfunction nearly at the same time. We administered azathioprine to our patient. Fortunately, the patient demonstrated a good response to azathioprine, including a partial reduction in proteinuria from ~ 12.5 g/D to 2.62 g/D after 21 months of observation and the improvement of liver function. Our findings suggest that azathioprine may be a suitable treatment option for patients presenting with coexisting PBC-AIH overlap syndrome and MN.
Asunto(s)
Glomerulonefritis Membranosa , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Humanos , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/tratamiento farmacológico , Azatioprina/uso terapéutico , Ácido Ursodesoxicólico , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Resultado del Tratamiento , SíndromeRESUMEN
The A20 protein is considered to have a potent anti-inflammatory effect, but its mechanism of action in the regulation of ferroptosis and inflammation after stroke is still unknown. In this study, the A20-knockdown BV2 cell line (sh-A20 BV2) was constructed at first, and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model was constructed. Both the BV2 and sh-A20 BV2 cells were treated with the ferroptosis inducer erastin for 48 h, the ferroptosis-related indicators were detected by western blot. The mechanism of ferroptosis was explored by western blot and immunofluorescence. Under OGD/R pressure, the oxidative stress level of sh-A20 BV2 cells was inhibited, but the secretion of the inflammatory factors TNF-α, IL-1ß, and IL-6 was significantly upregulated. And sh-A20 BV2 cells had higher expression levels of GPX4 and NLRP3 proteins under OGD/R induction. Western blot further confirmed that sh-A20 BV2 cells inhibited OGD/R-induced ferroptosis. Under the effect of erastin of the ferroptosis inducer (0-1000 nM), sh-A20 BV2 cells had higher cell viability than wild-type BV2 cells and significantly inhibited the accumulation of ROS and the level of oxidative stress damage. It was confirmed that A20 could promote the activation of the IκBα/NFκB/iNOS pathway. It was confirmed by an iNOS inhibitor that iNOS inhibition could reverse the resistance effect of BV2 cells to OGD/R-induced ferroptosis after A20 knockdown. In conclusion, this study demonstrated that inhibition of A20 mediates a stronger inflammatory response while enhancing microglial resistance by knocking down A20 in BV2 cells.
Asunto(s)
Ferroptosis , Accidente Cerebrovascular , Humanos , Microglía/metabolismo , FN-kappa B/metabolismo , Línea CelularRESUMEN
BACKGROUND: HIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu'er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance. METHODS: A cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu'er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm. RESULTS: A total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM. CONCLUSION: The overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , China/epidemiología , Estudios Transversales , Farmacorresistencia Viral/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Seropositividad para VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
Planetary boundary-layer height is an important physical quantity for weather forecasting models and atmosphere environment assessment. A method of simultaneously extracting the surface-layer height (SLH), mixed-layer height (MLH), and aerosol optical properties, which include aerosol extinction coefficient (AEC) and aerosol optical depth (AOD), based on the signal-to-noise ratio (SNR) of the same coherent Doppler wind lidar (CDWL) is proposed. The method employs wavelet covariance transform to locate the SLH and MLH using the local maximum positions and an automatic algorithm of dilation operation. AEC and AOD are determined by the fitting curve using the SNR equation. Furthermore, the method demonstrates the influential mechanism of optical properties on the SLH and MLH. MLH is linearly correlated with AEC and AOD because of solar heating increasing. The results were verified by the data of an ocean island site in China.
RESUMEN
HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (⩾10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.
Asunto(s)
Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Adolescente , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , China/epidemiología , Femenino , Infecciones por VIH/epidemiología , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Adulto JovenRESUMEN
It is worth highlighting that, for the first time to the best of our knowledge, vertical profiles of atmospheric parameters and $C_n^2$ were measured at Lhasa, south of the Tibetan Plateau, using balloon-borne radiosondes. Based on the measurements, two new statistical models (Lhasa HMN and Lhasa Dewan) for estimating turbulence strength are proposed. Attention has been paid to evaluate the reliability of the two models to reconstruct vertical profiles of $C_n^2$ from a statistical perspective. The statistical analyses presenting the Lhasa HMN model are accompanied with lower bias, root mean square error (RMSE), and bias-corrected RMSE ($\sigma$) than those of the Lhasa Dewan model, which implies the Lhasa HMN model can better reveal the nature of turbulence characteristics of Lhasa influenced by unique local weather conditions. In addition, the comparison between the Lhasa HMN model and measurements in calculating integrated astroclimatic parameters is carried out, and the result suggests that the performance of the Lhasa HMN model is reliable and satisfactory. The new reliable $C_n^2$ model offers new insight into the characteristics of optical turbulence at Lhasa and provides support for pursuing astronomical site selection in the Tibetan Plateau.
RESUMEN
BACKGROUND: As a gateway for HIV-1 in China, Yunnan has experienced dramatic changes in HIV-1 epidemics, during which HIV-1 genotypes have become complex. To track dynamic changes in HIV-1 genotypes, an HIV-1 molecular epidemiological study was implemented in the recently infected population in Yunnan. METHODS: From 6,357 HIV-1-positive samples diagnosed during the first half of 2015 in Yunnan, 586 samples were identified as recent infections with BED-capture enzyme immunoassay (CEIA) and were subjected to phylogenetic analyses. Spatial scanning analyses for the main HIV-1 genotypes were also performed. RESULTS: Among the 439 specimens successfully genotyped, more than ten genotypes were detected, including CRF08_BC (45.3%), CRF07_BC (19.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (11.4%), subtype C (2.1%), CRF85_BC (1.1%), CRF55_01B (0.9%), subtype B (0.5%), CRF64_BC (0.5%), CRF59_01B (0.2%), CRF83_cpx (0.2%) and CRF87_cpx (0.2%). Females, Chinese, heterosexual contact and intravenous drug injection were significantly associated with CRF08_BC infection; homosexual contact was significantly associated with CRF01_AE and CRF07_BC infection; males and non-Chinese had a higher risk of URF infection than females. Among all HIV-1 genotypes, the geographic coverage of CRF08_BC was the largest. For CRF08_BC, CRF07_BC, URFs and CRF01_AE, spatial clusters were detected. The two CRF08_BC clusters and one URF cluster were associated with heterosexual transmission, and two of CRF01_AE clusters were associated with homosexual transmission. Transmitted drug resistance (TDR)-associated mutations were detected in 2.4% of individuals. CONCLUSIONS: The diversity of HIV-1 genotypes increased in recent infections because of a long-term HIV-1 epidemic in Yunnan. The predominant HIV-1 strains showed distinct demographic characteristics and formed spatial clusters. These findings improved our understanding of the evolution of HIV-1 in Yunnan and provided information for further HIV-1 control and prevention.
Asunto(s)
Farmacorresistencia Viral/genética , Epidemias , Variación Genética , Infecciones por VIH/virología , VIH-1/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Genotipo , Infecciones por VIH/epidemiología , VIH-1/clasificación , Heterosexualidad , Homosexualidad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Filogenia , Análisis Espacial , Adulto JovenRESUMEN
BACKGROUND: The characteristics of recent HIV infections can provide the information about the dynamics of HIV transmission. Yunnan is one of the provinces hardest-hit by HIV-1 in China. To further understand the characteristics of the HIV-1 epidemic in Yunnan, we analyzed the prevalence of recent HIV-1 infections among newly diagnosed cases, identified the associated factors and explored the spatial distribution of recent HIV-1 infections. METHODS: Residual plasma samples from HIV-1 diagnostic tests were preserved. The associated information was collected from China HIV/AIDS case reporting system. Recent HIV-1 infections were estimated by combining the information about disease progression and BED- capture enzyme immunoassay (CEIA). The proportions of recent HIV-1 infections among newly diagnosed cases stratified by demographic characteristics were analyzed. The spatial clusters of recent HIV-1 infections were investigated by spatial scan statistics. RESULTS: Among 6119 HIV/AIDS cases were newly reported between January 2015 and June 2015 in Yunnan Province, 9.3% (570/6119) were estimated as recent infections. Female, aged below 25 years and homosexual contact were more associated with the higher proportion of recent HIV-1 infections. Among the different demographic sub-groups, men who have sex with men (MSM) aged < 25 years and ≥ 50 years had a higher chance of being diagnosed as recent infections, heterosexually infected men aged ≥25 years had a lower chance of being diagnosed as recent infections. In the sub-groups with different screening approaches, the highest proportion of recent infections (16.1%) was found among women diagnosed by testing during pregnancy and childbirth. In the sub-groups with different contact histories, the higher proportion of recent infections was found among the female cases having commercial heterosexual contacts (16.4%) and MSM (19.7%). The statistically significant spatial clusters of recent infections attributed to heterosexual contact, homosexual contact and intravenous drug injection were identified, respectively. CONCLUSIONS: The investigation of recent HIV infections among newly diagnosed cases supplements the routine HIV surveillance, and reveals the characteristics of ongoing HIV transmission. Our finding identified the potential sub-populations and geographic areas in need of services or improved interventions.
Asunto(s)
Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , VIH-1 , Conducta Sexual/estadística & datos numéricos , Minorías Sexuales y de Género/estadística & datos numéricos , Adulto , Distribución por Edad , China/epidemiología , Femenino , Heterosexualidad/estadística & datos numéricos , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Prevalencia , Análisis Espacial , Adulto JovenRESUMEN
Purpose: To explore the relationship between obstructive sleep apnea (OSA) and hypoperfusion during ultra-early acute cerebral infarction. Patients and methods: Data were retrospectively collected from patients admitted to our hospital with acute cerebral infarction between January 2020 and January 2022, who underwent comprehensive whole-brain computed tomography perfusion imaging and angiography examinations within 6 h of onset. The F-stroke software automatically assessed and obtained relevant data (Tmax). The patients underwent an initial screening for sleep apnea. Based on their Apnea-Hypopnea Index (AHI), patients were categorized into an AHI ≤15 (n = 22) or AHI >15 (n = 25) group. The pairwise difference of the time-to-maximum of the residue function (Tmax) > 6 s volume was compared, and the correlation between AHI, mean pulse oxygen saturation (SpO2), oxygen desaturation index (ODI), percentage of time with oxygen saturation < 90% (T90%), and the Tmax >6 s volume was analyzed. Results: The Tmax >6 s volume in the AHI > 15 group was significantly larger than that in the AHI ≤ 15 group [109 (62-157) vs. 59 (21-106) mL, p = 0.013]. Spearman's correlation analysis revealed Tmax >6 s volume was significantly correlated with AHI, mean SpO2, ODI, and T90% in the AHI > 15 group, however, no significant correlations were observed in the AHI ≤ 15 group. Controlling for the site of occlusion and Multiphase CT angiography (mCTA) score, AHI (ß = 0.919, p < 0.001), mean SpO2 (ß = -0.460, p = 0.031), ODI (ß = 0.467, p = 0.032), and T90% (ß =0.478, p = 0.026) remained associated with early hypoperfusion in the AHI > 15 group. Conclusion: In patients with acute cerebral infarction and AHI > 15, AHI, mean SpO2, ODI and T90% were associated with early hypoperfusion. However, no such relationship exists among patients with AHI ≤ 15.
RESUMEN
In order to better support the construction of the capital water conservation functional area and ecological environment support areaï¼ research on the chemical characteristics of groundwater and its formation mechanism in the dry period in the Zhangjiakou area can provide a great reference for the rational development and utilization of groundwater resources. A total of 41 groups of groundwater samples were collectedï¼ and the hydrochemical typesï¼ composition characteristicsï¼ and control factors of groundwater in the study area were analyzed by using the combined method of descriptive statistical analysisï¼ Piper triplotï¼ correlation analysisï¼ Gibbs plotï¼ and ion ratio. The results showed that the groundwater in the study area was weakly alkalineï¼ with the total hardness and ρï¼TDSï¼ ranging from 105.00 mg·L-1 to 1 433.00 mg·L-1 and 137.00 mg·L-1 to 2 286.00 mg·L-1ï¼ respectively. The total hardness and TDS mass concentrations of groundwater in the Bashang area were higher than those in the Baxia area. HCO3- and Na+ were the main dominant anions and cations in the groundwater in the study area. The highest overstandard rate of the main components in groundwater was that of total hardness ï¼36.59%ï¼. The overstandard rate and maximum excess multiple of each component in groundwater in the Bashang area were greater than those in the Baxia area. HCO3-Ca·Mg·Na was the main type of groundwater hydrochemistry in the study areaï¼ and there was little difference between the Bashang area and the Baxia area. SO42-ï¼ Cl-ï¼ HCO3-ï¼ Na+ï¼ and Mg2+ contributed the most to TDS. The chemical characteristics of groundwater were affected by weathering and filtration of rock minerals such as salt rockï¼ albiteï¼ and dolomiteï¼ cation exchangeï¼ and human activities. Evaporative crystallization and atmospheric precipitation contributed to a small part of the main ion source of groundwater in the area. The effect of human activities on groundwater in the Bashang area was greater than that in the Baxia areaï¼ and NO3- mainly originated from agricultural activities.
RESUMEN
The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.
RESUMEN
BACKGROUND: The China-Myanmar border area is considered a hot spot of active HIV-1 recombination in Southeast Asia. To better understand the characteristics of HIV-1 transmission in this area, a cross-sectional HIV-1 molecular epidemiological survey was conducted in Baoshan Prefecture of Yunnan Province. METHODS: In total, 708 newly reported HIV-1 cases in Baoshan Prefecture from 2019 to 2020 were included in this study. HIV-1 gag, pol and env genes were sequenced, and the spatial and demographic distributions of HIV-1 genotypes were analyzed. The characteristics of HIV-1 transmission were investigated using the HIV-1 molecular network method. RESULTS: In the 497 samples with genotyping results, 19 HIV-1 genotypes were found, with URFs being the predominant strains (30.2%, 150/497). The main circulating HIV-1 strains were mostly distributed in the northern area of Baoshan. URFs were more likely identified in Burmese individuals, intravenous drug users and those younger than 50 years old. CRF08_BC was more likely detected in farmers and those of Han ethnicity, CRF01_AE in the young and those of Han ethnicity, and CRF07_BC in the subpopulation with junior middle school education and higher. Moreover, CRF118_BC and CRF64_BC were more likely found in the subpopulation aged ≥40 years and ≥50 years, respectively. Among 480 individuals with pol sequence detection, 179 (37.3%) were grouped into 78 clusters, with Baoshan natives being more likely to be in the network. The proportion of the linked individuals showed significant differences when stratified by the regional origin, marital status, age and county of case reporting. In the molecular network, recent infections were more likely to occur among nonfarmers and individuals aged below 30 years. CONCLUSIONS: HIV-1 genetics has become complex in Baoshan. HIV-1 molecular network analysis provided transmission characteristics in the local area, and these findings provided information to prioritize transmission-reduction interventions.
Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , China/epidemiología , Estudios Transversales , Genotipo , Infecciones por VIH/epidemiología , VIH-1/genética , Humanos , Persona de Mediana Edad , Mianmar/epidemiología , FilogeniaRESUMEN
OBJECTIVE: To study the mechanisms of Danggui Shaoyao San (DSS) on Alzheimer's diseases (AD) focusing on anti-inflammation. METHOD: AD rats were established by intrahippocampal bilateral injection of Abeta1-42 protein. The AD rats were randomly divided into three groups: AD model group, DSS high-dose group, DSS low-dose group. Vehicle group rats were intrahippocampal bilateral injection of solvent with the same dose. The learning ability and memory of rats was investigated in step-down passive avoidance test and Morris water maze test, expression of IL-1beta, IL-6, TNF-alpha mRNA were observed by reverse transcriptase PCR (RT-PCR), levels of NO was measured by colorimetric method and neuron apoptosis in the hippocampus was investigated by tag method of TdT-mediated end-labeling of fragmented DNA (TUNEL). RESULT: DSS significantly reduced the escape latency and increased the time that rats spent in the target quadrant in Morris water maze test, shortened the responsive latency and decreased the error numbers in step-down passive avoidance test, reduced the expression of the IL-1beta, IL-6, TNF-alpha mRNA, and the level of the NO depressed the neuron apoptosis in the hippocampus. CONCLUSION: DSS improving cognition of the rats might be related to attenuate inflammatory reaction and reduce cell apoptosis in the hippocampus.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Animales , Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Yunnan has the greatest share of reported human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) cases in China. In recent years, HIV prevalence and incidence remained stubbornly high in men who have sex with men (MSM). To follow the dynamics of the HIV-1 epidemic among MSM, HIV-1 genetic characteristics and genetic transmission networks were investigated. METHODS: Blood samples from 190 newly diagnosed HIV-1 cases among MSM were continuously collected at fixed sites from January 2013 to December 2015 in Kunming City, Yunnan Province. Partial gag, pol and env genes were sequenced and used for phylogenetic and genotypic drug resistance analyses. The genetic characteristics of the predominant HIV-1 strains were analyzed by the Bayesian Markov Chain Monte Carlo (MCMC) method. The genetic transmission networks were identified with a genetic distance of 0.03 substitutions/site and 90% bootstrap support. RESULTS: Among the 190 HIV-1 positive MSM reported during 2013-2105, various genotypes were identified, including CRF01_AE (45.3%), CRF07_BC (35.8%), unique recombinant forms (URFs) (11.6%), CRF08_BC (3.2%), CRF55_01B (2.1%), subtype B (1.6%) and CRF59_01B (0.5%). The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially from approximately 2001-2010 and 2005-2009, respectively. Genetic transmission networks were constructed with 308 pol sequences from MSM diagnosed during 2010-2015. Of the 308 MSM, 109 (35.4%) were identified in 38 distinct clusters. Having multiple male partners was associated with a high probability of identification in the genetic transmission networks. Of the 38 clusters, 27 (71.1%) contained individuals diagnosed in different years. Of the 109 individuals in the networks, 26 (23.9%) had ≥2 potential transmission partners (≥2 links). The proportion of MSM with ≥2 links was higher among those diagnosed from 2010-2012. The constituent ratios of their potential transmission partners by areas showed no significant difference among MSM from Kunming, other cities in Yunnan and other provinces. Additionally, surveillance drug resistance mutations (SDRMs) were identified in 5% of individuals. CONCLUSION: This study revealed the various HIV-a genotypes circulating among MSM in Kunming. MSM with more partners were more easily detected in transmission networks, and early-diagnosed MSM remained active in transmission networks. These findings suggested that the routine interventions should be combined with HIV testing and linkage to care and early antiretroviral therapy among HIV-positive MSM.
Asunto(s)
Infecciones por VIH/transmisión , VIH-1/genética , Adolescente , Adulto , Anciano , China , Farmacorresistencia Viral/genética , Genotipo , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Método de Montecarlo , Probabilidad , ARN Viral/química , ARN Viral/metabolismo , Análisis de Secuencia de ADN , Adulto Joven , Productos del Gen env del Virus de la Inmunodeficiencia Humana/clasificación , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/clasificación , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/clasificación , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Cumarinas/farmacología , Hipocalcina/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Antioxidantes/administración & dosificación , Infarto Encefálico/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cumarinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Ácido Glutámico/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis.
Asunto(s)
Asma/terapia , Inmunoterapia/métodos , Interleucinas/antagonistas & inhibidores , Interleucinas/inmunología , Receptores de Interleucina/antagonistas & inhibidores , Transducción de Señal , Vacunas de Partículas Similares a Virus/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Interleucinas/genética , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/genética , Virosomas/ultraestructuraRESUMEN
OBJECTIVE: Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections. METHODS: Mice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay. RESULTS: Intramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates. CONCLUSIONS: Utilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections.