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1.
Methods Mol Biol ; 2854: 237-251, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39192134

RESUMEN

The innate immune system is the first line of host defense against infection by pathogenic microorganisms, among which macrophages are important innate immune cells. Macrophages are widely distributed throughout the body and recognize and eliminate viruses through pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs). In the present chapter, we provide detailed protocols for vesicular stomatitis virus (VSV) amplification, VSV titer detection, isolation of mouse primary peritoneal macrophages, in vitro and in vivo VSV infection, detection of interferon-beta (IFN-ß) expression, and lung injury. These protocols provide efficient and typical methods to evaluate virus-induced innate immunity in vitro and in vivo.


Asunto(s)
Inmunidad Innata , Interferón beta , Macrófagos Peritoneales , Vesiculovirus , Animales , Ratones , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/virología , Macrófagos Peritoneales/metabolismo , Interferón beta/inmunología , Interferón beta/metabolismo , Interferón beta/genética , Vesiculovirus/inmunología , Vesiculovirus/genética , Estomatitis Vesicular/inmunología , Estomatitis Vesicular/virología , Virus de la Estomatitis Vesicular Indiana/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Receptores de Reconocimiento de Patrones/inmunología
3.
Int J STD AIDS ; : 9564624241287260, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39361066

RESUMEN

BACKGROUND: HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. PATIENTS AND METHODS: A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. RESULTS: HIV-positive patients were 20 years younger than HIV-negative patients (p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival (p = 0.022); rates of cure (p = 0.933) and recurrence rates (p = 0.8) were similar in HIV-positive and negative women. CONCLUSIONS: Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.

4.
Int Med Case Rep J ; 17: 801-807, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355258

RESUMEN

Background: Fulminant hepatitis is a rare and severe form of acute liver failure (ALF) characterized by rapid and massive destruction of liver cells and associated with a high mortality rate. Infectious factors, in particular viral hepatitis, take a prominent place in the etiology of ALF, however, the presence of chronic liver pathology can play a significant role in the disease progression and development of ALF. Case Presentation: A 2-year-old child was hospitalized on the 4th day of the disease with manifestations of jaundice and general intoxication. The examination revealed markers of active hepatitis A virus infection and Epstein-Barr virus infection. From the seventh day of the disease, the child's condition began to progressively deteriorate due to manifestations of ALF. Despite the use of immunomodulatory and replacement therapy, the disease ended fatally on the 9th day. Pathohistological examination revealed manifestations of viral necrotic hepatitis on the background of autoimmune sclerosing cholangitis. Conclusion: The case is novel as regards the occurrence of two viral hepatitis with different modes of transmission on a background of unidentified liver disease.

5.
Front Microbiol ; 15: 1469016, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309526

RESUMEN

The integration of Hepatitis B Virus (HBV) is now known to be closely associated with the occurrence of liver cancer and can impact the functionality of liver cells through multiple dimensions. However, despite the detailed understanding of the characteristics of HBV integration and the mechanisms involved, the subsequent effects on cellular function are still poorly understood in current research. This study first systematically discusses the relationship between HBV integration and the occurrence of liver cancer, and then analyzes the status of the viral genome produced by HBV replication, highlighting the close relationship and structure between double-stranded linear (DSL)-HBV DNA and the occurrence of viral integration. The integration of DSL-HBV DNA leads to a certain preference for HBV integration itself. Additionally, exploration of HBV integration hotspots reveals obvious hotspot areas of HBV integration on the human genome. Virus integration in these hotspot areas is often associated with the occurrence and development of liver cancer, and it has been determined that HBV integration can promote the occurrence of cancer by inducing genome instability and other aspects. Furthermore, a comprehensive study of viral integration explored the mechanisms of viral integration and the internal integration mode, discovering that HBV integration may form extrachromosomal DNA (ecDNA), which exists outside the chromosome and can integrate into the chromosome under certain conditions. The prospect of HBV integration as a biomarker was also probed, with the expectation that combining HBV integration research with CRISPR technology will vigorously promote the progress of HBV integration research in the future. In summary, exploring the characteristics and mechanisms in HBV integration holds significant importance for an in-depth comprehension of viral integration.

6.
ACS Nano ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315858

RESUMEN

Influenza virus (IV) infection currently poses a serious and continuing threat to the global public health. Developing effective prevention strategies is important to defend against infection and spread of IV. Here, we developed a triple-protective nanoshield against IV infection in the lungs, formed by self-assembling DSPE-PEG amphiphilic polymers encapsulating the flu-preventive antiviral drug Arbidol internally. The preventive effect of the nanoshield against virus infection includes increasing the viscosity in the surrounding environment to physically defend against viral entry, forming a hydrated layer to block the interaction between viruses and cells, and inhibiting virus replication. Our finding suggested that a single inhalation of the nanoshield provides effective protection against IV infection for at least 8 h. Thus, this nanoshield may be a potential pandemic protection agent against IV, especially in viral environments, where no prophylactic or therapeutic measures are available.

7.
Front Microbiol ; 15: 1458754, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323880

RESUMEN

Background: Research on the effects of intestinal microbiota transplantation (IMT) on chronic HBV infection (CHB) progression associated liver disease (HBV-CLD) and alterations in the microbiota post-IMT are quite limited for the moment. Methods: By integrating microbiome with metabolome analyses, we aimed to the function of IMT and the alterations of gut microbiota in patients with HBV-CLD. First, this study included 20 patients with HBV-CLD and ten healthy controls. Then, 16 patients with CHB were given IMT with donor feces (heterologous) via oral capsule. Fecal samples from CHB patients were obtained before and after IMT, as well as healthy controls, for 16S rDNA sequencing and untargeted metabolomics analysis. Results: The proalbuminemia were significantly increased after IMT, and the HBsAg and TBA showed a significant decrease after IMT in the HBV-CLD patients. There was statistical difference in the Chaol indexes between between CHB patients and healthy controls, suggesting a lower abundance of the gut microbiota in HBV-CLD patients. In addition, there was statistical difference in the Shannon and Simpson indexes between prior to IMT and post-IMT, indicating that the impaired abundance of the gut microbiota had been improved after IMT. The host-microbiota-metabolite interplay, amino acid metabolism, nicotinate and nicotinamide metabolism, starch and sucrose metabolism, steroid biosynthesis, and vitamins metabolism, were significantly lower in HBV-CLD patients than healthy controls. Conclusion: IMT may improve the therapeutic effects on patients HBV-CLD. Furthermore, IMT appears to improve amino acid metabolism by impaired abundance of the gut microbiota and therefore improve liver prealbumin synthesis.

8.
Front Plant Sci ; 15: 1421221, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224853

RESUMEN

Eukaryotic elongation factors (eEFs) are protein factors that mediate the extension of peptide chain, among which eukaryotic elongation factor 1 alpha (eEF1A) is one of the most abundant protein synthesis factors. Previously we showed that the P3 protein of Soybean mosaic virus (SMV), one of the most destructive and successful viral pathogens of soybean, targets a component of the soybean translation elongation complex to facilitate its pathogenesis. Here, we conducted a systematic analyses of the soybean eEF (GmeEF) gene family in soybean and examinedits role in virus resistance. In this study, GmeEF family members were identified and characterized based on sequence analysis. The 42 members, which were unevenly distributed across the 15 chromosomes, were renamed according to their chromosomal locations. The GmeEF members were further divided into 12 subgroups based on conserved motif, gene structure, and phylogenetic analyses. Analysis of the promoter regions showed conspicuous presence of myelocytomatosis (MYC) and ethylene-responsive (ERE) cis-acting elements, which are typically involved in drought and phytohormone response, respectively, and thereby in plant stress response signaling. Transcriptome data showed that the expression of 15 GmeEF gene family members changed significantly in response to SMV infection. To further examine EF1A function in pathogen response, three different Arabidopsis mutants carrying T-DNA insertions in orthologous genes were analyzed for their response to Turnip crinkle virus (TCV) and Cucumber mosaic virus (CMV). Results showed that there was no difference in viral response between the mutants and the wild type plants. This study provides a systematic analysis of the GmeEF gene family through analysis of expression patterns and predicted protein features. Our results lay a foundation for understanding the role of eEF gene in soybean anti-viral response.

9.
Biol Sex Differ ; 15(1): 69, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237981

RESUMEN

BACKGROUND: Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. METHODS: We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. RESULTS: We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. CONCLUSION: According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.


Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). It can lead to long-term liver damage and cancer. We looked at differences in how the virus affects men and women in Taiwan. We analyzed data from over 72,000 people in the Taiwan Biobank. The study individuals were divided into two groups­those who had the hepatitis B virus (cases) and those who did not (controls). We looked for genetic differences between the two groups and found that the specific genetic risk factors for hepatitis B differed between men and women. We found three genetic risk factors in men and eight in women. This suggests that the way the hepatitis B virus interacts with our genes may differ between the sexes. We found that in women, the most significant genetic risk factors were all located on chromosome 6. However, in men, the significant risk factors were spread across different chromosomes, including chromosome 3. Finally, we looked at how these genetic differences might affect the way the body processes the hepatitis B virus. We found that two specific genes, called POGLUT1 and HIST1H2BC, were only linked to hepatitis B risk in men, not in women. This indicates that the biological pathways involved in hepatitis B infection may differ between males and females. Understanding these differences could lead to more effective, personalized treatment strategies for those affected by the virus.


Asunto(s)
Hepatitis B Crónica , Receptores Notch , Caracteres Sexuales , Transducción de Señal , Humanos , Masculino , Femenino , Taiwán , Hepatitis B Crónica/genética , Hepatitis B Crónica/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Persona de Mediana Edad , Adulto , Bancos de Muestras Biológicas , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Virus de la Hepatitis B
10.
Front Artif Intell ; 7: 1405332, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282474

RESUMEN

Introduction: This study introduces the Supervised Magnitude-Altitude Scoring (SMAS) methodology, a novel machine learning-based approach for analyzing gene expression data from non-human primates (NHPs) infected with Ebola virus (EBOV). By focusing on host-pathogen interactions, this research aims to enhance the understanding and identification of critical biomarkers for Ebola infection. Methods: We utilized a comprehensive dataset of NanoString gene expression profiles from Ebola-infected NHPs. The SMAS system combines gene selection based on both statistical significance and expression changes. Employing linear classifiers such as logistic regression, the method facilitates precise differentiation between RT-qPCR positive and negative NHP samples. Results: The application of SMAS led to the identification of IFI6 and IFI27 as key biomarkers, which demonstrated perfect predictive performance with 100% accuracy and optimal Area Under the Curve (AUC) metrics in classifying various stages of Ebola infection. Additionally, genes including MX1, OAS1, and ISG15 were significantly upregulated, underscoring their vital roles in the immune response to EBOV. Discussion: Gene Ontology (GO) analysis further elucidated the involvement of these genes in critical biological processes and immune response pathways, reinforcing their significance in Ebola pathogenesis. Our findings highlight the efficacy of the SMAS methodology in revealing complex genetic interactions and response mechanisms, which are essential for advancing the development of diagnostic tools and therapeutic strategies. Conclusion: This study provides valuable insights into EBOV pathogenesis, demonstrating the potential of SMAS to enhance the precision of diagnostics and interventions for Ebola and other viral infections.

11.
BMC Infect Dis ; 24(1): 968, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271979

RESUMEN

INTRODUCTION: In Sub-Saharan Africa alone, about 40-65% of Hepatitis B Virus infections among HCWs were a result of percutaneous occupational exposures to contaminated blood and body fluids of patients. Occupational exposure to blood and body fluids among healthcare workers is on the rise in Ghana. However, the relationship between self-reported exposures to blood and body fluids suspected to be contaminated with the hepatitis B virus and actual serological evidence of exposure remains unknown. The aim of the study however was to assess the self-reported exposure to HBV as against the serological evidence of lifetime exposure to HBV and associated factors among Ghanaian HCWs. METHODS: The study was a cross-sectional analytical survey that involved 340 HCWs who were recruited using a simple random sampling procedure from six cadres of staff from five districts in Greater Accra. The participants were surveyed using a validated instrument and 5mls of venous blood was aseptically withdrawn for qualitative detection of Anti-HBc. SPSS version 23.0 was used to analyze the data to obtain proportions, odds ratios and their corresponding confidence intervals with the level of significance set at 0.05. RESULTS: The response rate was 94% with Nurses and Doctors in the majority with a mean age of 35.6 ± 7.2. Self-reported exposure to HBV was 63% whereas lifetime exposure to HBV (Anti-HBc) prevalence was 8.2% (95% CI = 5.0-11.0%). Females were 60% less likely to be exposed to HBV (aOR = 0.4; 95% CI = 0.1-0.9) than their male counterparts. HCWs without training in the prevention of blood-borne infections had almost three times higher odds of being exposed to HBV in their lifetime (aOR = 2.6; 95% CI = 1.0-6.4). CONCLUSIONS: The findings of this study suggest that self-reported exposure to HBV-contaminated biological materials was high with a corresponding high lifetime exposure to HBV. The female gender was protective of anti-HBc acquisition. Apart from direct interventions for preventing occupational exposures to HBV in the healthcare setting, periodic training of all categories of healthcare workers in infection prevention techniques could significantly reduce exposure to the Hepatitis B virus.


Asunto(s)
Personal de Salud , Hepatitis B , Exposición Profesional , Autoinforme , Humanos , Estudios Transversales , Ghana/epidemiología , Femenino , Masculino , Personal de Salud/estadística & datos numéricos , Adulto , Hepatitis B/epidemiología , Hepatitis B/transmisión , Exposición Profesional/estadística & datos numéricos , Persona de Mediana Edad , Líquidos Corporales/virología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Adulto Joven , Anticuerpos contra la Hepatitis B/sangre
12.
Virology ; 600: 110233, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39255726

RESUMEN

Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39297586

RESUMEN

OBJECTIVE: Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. METHODS: A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People's Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. RESULTS: The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). CONCLUSION: MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

15.
BMC Infect Dis ; 24(1): 957, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261777

RESUMEN

PURPOSE: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. METHODS: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. RESULTS: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). CONCLUSION: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive.


Asunto(s)
Amniocentesis , ADN Viral , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Carga Viral , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Recién Nacido , Hepatitis B/transmisión , Adulto , Antígenos de Superficie de la Hepatitis B/sangre , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Antivirales/uso terapéutico , Masculino , Madres , Adulto Joven
17.
World J Gastroenterol ; 30(26): 3193-3197, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39086636

RESUMEN

In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the problem of occult hepatitis B virus (HBV) infection, that is a result of previous hepatitis B (PHB) and a source for reactivation of HBV. The prevalence of PHB is underestimated due to the lack of population testing programs. However, this condition not only complicate anticancer treatment, but may be responsible for the development of other diseases, like cancer or autoimmune disorders. Here we unveil possible mechanisms responsible for realization of these processes and suggest practical approaches for diagnosis and treatment.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Activación Viral , Humanos , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis B/epidemiología , Hepatitis B/virología , Hepatitis B/diagnóstico , Antivirales/uso terapéutico , Prevalencia
18.
Adv Exp Med Biol ; 1448: 481-496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39117835

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disease caused by mutations in effectors and regulators of cytotoxicity in cytotoxic T cells (CTL) and natural killer (NK) cells. The complexity of the immune system means that in vivo models are needed to efficiently study diseases like HLH. Mice with defects in the genes known to cause primary HLH (pHLH) are available. However, these mice only develop the characteristic features of HLH after the induction of an immune response (typically through infection with lymphocytic choriomeningitis virus). Nevertheless, murine models have been invaluable for understanding the mechanisms that lead to HLH. For example, the cytotoxic machinery (e.g., the transport of cytotoxic vesicles and the release of granzymes and perforin after membrane fusion) was first characterized in the mouse. Experiments in murine models of pHLH have emphasized the importance of cytotoxic cells, antigen-presenting cells (APC), and cytokines in hyperinflammatory positive feedback loops (e.g., cytokine storms). This knowledge has facilitated the development of treatments for human HLH, some of which are now being tested in the clinic.


Asunto(s)
Síndrome de Liberación de Citoquinas , Modelos Animales de Enfermedad , Linfohistiocitosis Hemofagocítica , Animales , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/genética , Ratones , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/patología , Citocinas/metabolismo , Citocinas/genética , Linfocitos T Citotóxicos/inmunología , Células Asesinas Naturales/inmunología
19.
Am J Physiol Lung Cell Mol Physiol ; 327(3): L406-L414, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39104315

RESUMEN

Obesity is a risk factor for increased morbidity and mortality in viral respiratory infection. Mucociliary clearance (MCC) in the airway is the primary host defense against viral infections. However, the impact of obesity on MCC is unclear, prompting this study. Using murine tracheal tissue culture and in vitro influenza A virus (IAV) infection models, we analyzed cilia-driven flow and ciliary beat frequency (CBF) in the airway epithelium to evaluate MCC. Short-term IAV infection increased cilia-driven flow and CBF in control mice, but not in high-fat diet-induced obese mice. Basal cilia-driven flow and CBF were also lower in obese mice than in control mice. Mechanistically, the increase of extracellular adenosine triphosphate (ATP) release during IAV infection, which was observed in the control mice, was abolished in the obese mice; however, the addition of ATP increased cilia-driven flow and CBF both in control and obese mice to a similar extent. In addition, RNA sequencing and reverse transcription-polymerase chain reaction revealed the downregulation of several cilia-related genes, including Dnah1, Dnal1, Armc4, and Ttc12 (the dynein-related genes); Ulk4 (the polychaete differentiation gene); Cep164 (the ciliogenesis and intraflagellar transport gene); Rsph4a, Cfap206, and Ppil6 (the radial spoke structure and assembly gene); and Drc3(the nexin-dynein regulatory complex genes) in obese murine tracheal tissues compared with their control levels. In conclusion, our studies demonstrate that obesity attenuates MCC under basal conditions and during IAV infection by downregulating the expression of cilia-related genes and suppressing the release of extracellular ATP, thereby increasing the susceptibility and severity of IAV infection.NEW & NOTEWORTHY Our study shows that obesity impairs airway mucociliary clearance (MCC), an essential physical innate defense mechanism for viral infection. Mechanically, this is likely due to the obesity-induced downregulation of cilia-related genes and attenuation of extracellular ATP release. This study provides novel insights into the mechanisms driving the higher susceptibility and severity of viral respiratory infections in individuals with obesity.


Asunto(s)
Cilios , Depuración Mucociliar , Obesidad , Mucosa Respiratoria , Animales , Cilios/metabolismo , Cilios/patología , Obesidad/metabolismo , Obesidad/patología , Obesidad/fisiopatología , Obesidad/complicaciones , Ratones , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Mucosa Respiratoria/virología , Ratones Endogámicos C57BL , Adenosina Trifosfato/metabolismo , Masculino , Tráquea/metabolismo , Tráquea/virología , Tráquea/patología , Virus de la Influenza A , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/metabolismo , Dieta Alta en Grasa/efectos adversos
20.
Clin Res Hepatol Gastroenterol ; 48(8): 102447, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39181184

RESUMEN

BACKGROUND: The hepatitis B surface antigen (HBsAg)-negative and antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). METHODS: To analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. RESULTS: HBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. CONCLUSION: The univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Hepatitis B , Leucemia , Activación Viral , Humanos , Masculino , Factores de Riesgo , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Persona de Mediana Edad , Hepatitis B/prevención & control , Leucemia/terapia , Virus de la Hepatitis B/fisiología , Adulto Joven , Trasplante Homólogo/efectos adversos , Anticuerpos contra la Hepatitis B/sangre , Estudios Retrospectivos , Adolescente , Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Incidencia
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