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International Journal of Molecular... Apr 2024The protective effects of hydrogen sulfide (HS) against ischemic brain injury and its role in promoting angiogenesis have been established. However, the specific...
The protective effects of hydrogen sulfide (HS) against ischemic brain injury and its role in promoting angiogenesis have been established. However, the specific mechanism underlying these effects remains unclear. This study is designed to investigate the regulatory impact and mechanism of HS on VEGFR2 phosphorylation. Following expression and purification, the recombinant His-VEGFR2 protein was subjected to LC-PRM/MS analysis to identify the phosphorylation sites of VEGFR2 upon NaHS treatment. Adenovirus infection was used to transfect primary rat brain artery endothelial cells (BAECs) with the Ad-VEGFR2, Ad-VEGFR2Y, and Ad-VEGFR2 plasmids. The expression of VEGFR2 and recombinant Flag-VEGFR2, along with Akt phosphorylation, cell proliferation, and LDH levels, was assessed. The migratory capacity and tube-forming potential of BAECs were assessed using wound healing, transwell, and tube formation assays. NaHS notably enhanced the phosphorylation of VEGFR2 at Tyr797 and Ser799 sites. These phosphorylation sites were identified as crucial for mediating the protective effects of NaHS against hypoxia-reoxygenation (H/R) injury. NaHS significantly enhanced the Akt phosphorylation, migratory capacity, and tube formation of BAECs and upregulated the expression of VEGFR2 and recombinant proteins. These findings suggest that Tyr797 and Ser799 sites of VEGFR2 serve as crucial mediators of HS-induced pro-angiogenic effects and protection against H/R injury.
Topics: Phosphorylation; Vascular Endothelial Growth Factor Receptor-2; Hydrogen Sulfide; Animals; Rats; Endothelial Cells; Neovascularization, Physiologic; Cell Movement; Rats, Sprague-Dawley; Cell Hypoxia; Cell Proliferation; Tyrosine; Proto-Oncogene Proteins c-akt; Reperfusion Injury; Angiogenesis Inducing Agents; Serine; Hypoxia
PubMed: 38673925
DOI: 10.3390/ijms25084340 -
International Journal of Molecular... Apr 2024The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a () infection. The influence of host-pathogen interactions on disease...
The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a () infection. The influence of host-pathogen interactions on disease progression remains unclear. It is important to note that infections following an HAdV-3E infection are frequently observed in clinical settings, yet the underlying susceptibility mechanisms are not fully understood. This study utilized an A549 cell model to investigate secondary infection with following an HAdV-3E infection. The findings suggest that HAdV-3E exacerbates the infection by intensifying lung epithelial cell damage. The results highlight the role of HAdV-3E in enhancing the interferon signaling pathway through (), resulting in the increased expression of interferon-stimulating factors like , , and . The increase in interferon-stimulating factors inhibits the NF-κB and MAPK/P38 pro-inflammatory signaling pathways. These findings reveal new mechanisms of action for HAdV-3E and in secondary infections, enhancing our comprehension of pathogenesis.
Topics: Humans; A549 Cells; Adaptor Proteins, Signal Transducing; Adenovirus Infections, Human; Adenoviruses, Human; Coinfection; DEAD Box Protein 58; Host-Pathogen Interactions; Inflammation; NF-kappa B; Receptors, Immunologic; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Ubiquitin Thiolesterase
PubMed: 38673764
DOI: 10.3390/ijms25084178 -
Virology Journal Apr 2024About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around... (Review)
Review
About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.
Topics: Humans; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccine Development; COVID-19 Drug Treatment; Antiviral Agents; Post-Acute COVID-19 Syndrome; Drug Repositioning
PubMed: 38671455
DOI: 10.1186/s12985-024-02370-6 -
Poultry Science Jun 2024Fowl adenovirus serotype 11 (FAdV-11) is one of the main causative agents of inclusion body hepatitis (IBH) in broilers. Outbreaks of FAdV-11-related IBH have been...
Fowl adenovirus serotype 11 (FAdV-11) is one of the main causative agents of inclusion body hepatitis (IBH) in broilers. Outbreaks of FAdV-11-related IBH have been increasingly reported in China and many other geographical areas worldwide. However, the critical virulence factors of FAdV-11 remain uncertain due to the lack of technical platforms for efficient manipulation of FAdV-11 genome. Here, we reported the establishment of a FAdV-11 reverse genetic system based on a novel FAdV-11 Chinese isolate FJSW/2021 using the exonuclease combined with RecET (ExoCET), Redαβ recombineering and ccdB counter-selection techniques for the first time. A recombinant FAdV-11 was rescued efficiently by using the established reverse genetic platform through swapping the ORF11 gene of the FAdV-11 FJSW/2021 with the ZsGreen fluorescent protein expression cassette. This study provides an effective technical platform for identifying virulence factors of FAdV-11 and developing recombinant FAdV-11-vectored vaccine candidates.
Topics: Animals; Poultry Diseases; Serogroup; Chickens; Adenoviridae Infections; Aviadenovirus; Reverse Genetics
PubMed: 38670058
DOI: 10.1016/j.psj.2024.103745 -
Poultry Science Jun 2024Fowl adenovirus serotype 4 (FAdV-4) infections result in substantial economic losses in the poultry industry. Recent findings have revealed that FAdV-4 significantly...
Fowl adenovirus serotype 4 (FAdV-4) infections result in substantial economic losses in the poultry industry. Recent findings have revealed that FAdV-4 significantly suppresses the host immune response upon infection; however, the specific viral and host factors contributing to this immunomodulatory activity remain poorly characterized. Moreover, diverse cell types exhibit differential immune responses to FAdV-4 infection. To elucidate cell-specific host responses, we performed transcriptomic analysis of FAdV-4 infected leghorn male hepatocellular (LMH) and chicken embryo fibroblast (CEF) cells. Although FAdV-4 replicated more efficiently in LMH cells, it provoked limited interferon-stimulated gene induction. In contrast, FAdV-4 infection triggered robust antiviral responses in CEF cells, including upregulation of cytosolic DNA sensing and interferon-stimulated genes. Knockdown of key cytosolic DNA sensing molecules enhanced FAdV-4 replication in LMH cells while reducing interferon-stimulated gene expression. Our findings reveal cell-specific virus-host interactions that provide insight into FAdV-4 pathogenesis while identifying factors that mediate antiviral immunity against FAdV-4.
Topics: Animals; Male; Immunity, Innate; Fibroblasts; Chick Embryo; Adenoviridae Infections; Poultry Diseases; Chickens; Aviadenovirus; Serogroup; Hepatocytes
PubMed: 38670055
DOI: 10.1016/j.psj.2024.103741 -
Infectious Disease Reports Mar 2024Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence... (Review)
Review
Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options.
PubMed: 38667752
DOI: 10.3390/idr16020026 -
EBioMedicine May 2024The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may...
BACKGROUND
The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens.
METHODS
Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array.
FINDINGS
Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients.
INTERPRETATION
ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study.
FUNDING
Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children's. BRACE trial funding is detailed in acknowledgements.
Topics: Humans; BNT162 Vaccine; COVID-19; SARS-CoV-2; Female; Male; Cytokines; Antibodies, Viral; ChAdOx1 nCoV-19; Adult; Middle Aged; Vaccination; COVID-19 Vaccines; Prospective Studies; Health Personnel; Spike Glycoprotein, Coronavirus
PubMed: 38663355
DOI: 10.1016/j.ebiom.2024.105100 -
Frontiers in Immunology 2024Human adenovirus type 7 (HAdV-7) is a significant viral pathogen that causes respiratory infections in children. Currently, there are no specific antiviral drugs or...
Human adenovirus type 7 (HAdV-7) is a significant viral pathogen that causes respiratory infections in children. Currently, there are no specific antiviral drugs or vaccines for children targeting HAdV-7, and the mechanisms of its pathogenesis remain unclear. The NLRP3 inflammasome-driven inflammatory cascade plays a crucial role in the host's antiviral immunity. Our previous study demonstrated that HAdV-7 infection activates the NLRP3 inflammasome. Building upon this finding, our current study has identified the L4 100 kDa protein encoded by HAdV-7 as the primary viral component responsible for NLRP3 inflammasome activation. By utilizing techniques such as co-immunoprecipitation, we have confirmed that the 100 kDa protein interacts with the NLRP3 protein and facilitates the assembly of the NLRP3 inflammasome by binding specifically to the NACHT and LRR domains of NLRP3. These insights offer a deeper understanding of HAdV-7 pathogenesis and contribute to the development of novel antiviral therapies.
Topics: Humans; Adenovirus Infections, Human; Adenoviruses, Human; HEK293 Cells; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Protein Binding; Viral Proteins; Viral Nonstructural Proteins
PubMed: 38660301
DOI: 10.3389/fimmu.2024.1294898 -
BMC Infectious Diseases Apr 2024Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in...
BACKGROUND
Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in children younger than five years old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury.
METHODS
In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated.
RESULTS
The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4 T cells.
CONCLUSIONS
The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4 T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.
Topics: Humans; Male; Female; Retrospective Studies; Child, Preschool; Infant; Length of Stay; Severity of Illness Index; Hospitalization; Adenovirus Infections, Human; Child; Liver; Adenoviridae Infections
PubMed: 38649842
DOI: 10.1186/s12879-024-09324-x -
BMC Infectious Diseases Apr 2024Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the...
BACKGROUND
Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020.
METHODS
Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records.
RESULTS
The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups.
DISCUSSION
In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.
Topics: Humans; China; Retrospective Studies; Respiratory Tract Infections; Male; Female; Middle Aged; Adult; Aged; Adolescent; Young Adult; Child; Child, Preschool; Acute Disease; Infant; Aged, 80 and over; Viruses; Hospitalization
PubMed: 38649799
DOI: 10.1186/s12879-024-09297-x