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Italian Journal of Pediatrics May 2024To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV).
BACKGROUND
To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV).
METHODS
The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves.
RESULTS
There was no difference between group A1 and group A2, group B1 and group B2 in terms of age, gender, duration of hospitalisation and fever. The levels of calcitoninogen(PCT), lactate dehydrogenase concentration(LDH), interleukin(IL)-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ in group A were higher than group B. The severe group (A1, B1) was significantly higher than the mild group (A2, B2) in terms of D-dimer, CRP, PCT, LDH, IL-6, IL-8, IL-10, IL-17a and number of patients with pleural effusion, solid lung changes. Among the individual indexes of D-dimer, CRP, N%,LDH, and PCT, the AUC of the combined test was 0.977, which was higher than that of the individual indicators. Among IL-6, IL-8, IL-10, and IL-17a, the AUC of the combined assay was 0.802, which was higher than that of the individual indicators.
CONCLUSION
MP combined with ADV infection was associated with increased expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, IFN-γ, and LDH. IL-6, IL-8, IL-10, IL-17a, LDH, PCT, CRP, and D-dimer could be used as predictors of SMPP and the combined test can improve the diagnostic value.
Topics: Humans; Male; Female; Pneumonia, Mycoplasma; Cytokines; Child; Child, Preschool; Biomarkers; Adenoviridae Infections; Severity of Illness Index; Coinfection; ROC Curve; Retrospective Studies
PubMed: 38715105
DOI: 10.1186/s13052-024-01661-6 -
Journal of Neuroinflammation May 2024Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating...
BACKGROUND
Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8 T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood-brain barrier disruption. However, the damage effect of CD8 T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8 T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8 T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8 T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8 T cells through up-regulating PD-L1 induced by IFNs.
METHODS
Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8 T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNβ or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro.
RESULTS
In vivo, ECM mice showed infiltration of activated CD8 T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8 T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNβ, IFNγ, or ECM CD8 T cells in vitro. Furthermore, the IFNβ or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8 T cell-mediated damage both in vitro and in vivo.
CONCLUSION
Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8 T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM.
Topics: Animals; Mice; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Interferon Regulatory Factor-1; Interferon-gamma; Malaria, Cerebral; Mice, Inbred C57BL; Mice, Knockout; Neurons; Plasmodium berghei; Signal Transduction; STAT1 Transcription Factor; Up-Regulation
PubMed: 38715061
DOI: 10.1186/s12974-024-03114-7 -
Vaccine May 2024It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this...
It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this study was to find the optimal dose regimen for the efficacy and safety of a mixture of previously developed recombinant adenovirus-based vaccines that expressed influenza nucleoprotein, hemagglutinin, and ectodomain of matrix protein 2 (rAd/NP and rAd/HA-M2e). The vaccine efficacy and safety were measured in the immunized mice with the mixture of rAd/NP and rAd/HA-M2e intranasally or intramuscularly. The minimum dose that would be efficacious in a single intranasal administration of the vaccine mixture and cross-protective efficacy against various influenza strains were examined. In addition, the immune responses that may affect the cross-protective efficacy were measured. We found that intranasal administration is an optimal route for 10 pfu of vaccine mixture, which is effective against pre-existing immunity against adenovirus. In a study to find the minimum dose with vaccine efficacy, the 10 pfu of vaccine mixture showed higher antibody titers to the nucleoprotein than did the same dose of rAd/NP alone in the serum of immunized mice. The 10 pfu of vaccine mixture overcame the morbidity and mortality of mice against the lethal dose of pH1N1, H3N2, and H5N1 influenza infections. No noticeable side effects were observed in single and repeated toxicity studies. We found that the mucosal administration of adenovirus-based universal influenza vaccine has both efficacy and safety, and can provide cross-protection against various influenza infections even at doses lower than those previously known to be effective.
Topics: Animals; Influenza Vaccines; Viral Matrix Proteins; Adenoviridae; Administration, Intranasal; Hemagglutinin Glycoproteins, Influenza Virus; Mice; Cross Protection; Antibodies, Viral; Orthomyxoviridae Infections; Female; Mice, Inbred BALB C; Influenza A Virus, H3N2 Subtype; Vaccines, Synthetic; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Vaccine Efficacy; Nucleoproteins; Viral Core Proteins; Injections, Intramuscular; Viroporin Proteins
PubMed: 38714444
DOI: 10.1016/j.vaccine.2024.04.054 -
Microbiology Spectrum Jun 2024Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing...
Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein-Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.IMPORTANCEGuidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.
Topics: Humans; Kidney Transplantation; Male; Middle Aged; Female; Transplant Recipients; Adult; Aged; BK Virus; Virus Diseases; Immunosuppression Therapy; Cytomegalovirus; Herpesvirus 4, Human; Retrospective Studies
PubMed: 38709030
DOI: 10.1128/spectrum.03575-23 -
Journal of Primary Care & Community... 2024In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders...
In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.
Topics: Adult; Female; Humans; Male; Middle Aged; COVID-19; COVID-19 Vaccines; Immunization, Secondary; Iran; SARS-CoV-2; Vaccination; Post-Acute COVID-19 Syndrome
PubMed: 38708693
DOI: 10.1177/21501319241251941 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Apr 2024To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory...
OBJECTIVE
To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis.
METHODS
We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed.
RESULTS
The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis ( < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models ( < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells ( < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models ( < 0.05).
CONCLUSION
KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.
Topics: Animals; Humans; Mice; Apoptosis Regulatory Proteins; Caco-2 Cells; Colitis; Crohn Disease; Disease Models, Animal; Inflammation; Intestinal Mucosa; Janus Kinase 2; Repressor Proteins; Signal Transduction; STAT3 Transcription Factor; Transcription Factors; Trinitrobenzenesulfonic Acid; Up-Regulation
PubMed: 38708511
DOI: 10.12122/j.issn.1673-4254.2024.04.19 -
BMC Pediatrics May 2024Acute gastroenteritis (AGE) causes significant morbidity in children worldwide; however, the disease burden of children hospitalized with viral gastroenteritis in China...
Changes in the epidemiology and clinical characteristics of viral gastroenteritis among hospitalized children in the Mainland of China: a retrospective study from 2016 to 2020.
BACKGROUND
Acute gastroenteritis (AGE) causes significant morbidity in children worldwide; however, the disease burden of children hospitalized with viral gastroenteritis in China has been rarely described. Through this study, we analyzed the data of hospitalized children with viral gastroenteritis to explore the changes in the epidemiology and clinical characteristics of viral gastroenteritis in the mainland of China.
METHODS
Data were extracted from Futang Children's Medical Development Research Center (FRCPD), between 2016 and 2020, across 27 hospitals in 7 regions. The demographics, geographic distribution, pathogenic examination results, complications, hospital admission date, length of hospital stays, hospitalization charges and outcomes were collected and analyzed.
RESULTS
Viral etiological agents included rotavirus (RV), adenovirus (ADV), norovirus (NV) and coxsackievirus (CV) that were detected in 25,274 (89.6%), 1,047 (3.7%), 441 (1.5%) and 83 (0.3%) cases. There was a higher prevalence of RV and NV infection among children younger than 3 years of age. RV and NV had the highest detection rates in winter, while ADV in summer. Children with viral gastroenteritis were often accompanied by other diseases, such as myocardial diseases (10.98-31.04%), upper respiratory tract diseases (1.20-20.15%), and seizures (2.41-14.51%). Among those cases, the co-infection rate with other pathogens was 6.28%, with Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), and influenza virus (FLU) being the most common pathogens. The median length of stay was 5 days, and the median cost of hospitalization corresponded to587 US dollars.
CONCLUSIONS
This finding suggests that viral gastroenteritis, especially those caused by RV, is a prevalent illness among younger children. Co-infections and the presence of other diseases are common. The seasonality and regional variation of viral etiological agents highlight the need for targeted prevention and control measures. Although viral gastroenteritis rarely leads to death, it also results in a significant economic burden on healthcare systems.
Topics: Humans; Gastroenteritis; China; Child, Preschool; Retrospective Studies; Infant; Male; Female; Child; Hospitalization; Length of Stay; Adolescent; Prevalence; Seasons; Infant, Newborn; Child, Hospitalized; Acute Disease; Rotavirus Infections
PubMed: 38704530
DOI: 10.1186/s12887-024-04776-1 -
Alternative Therapies in Health and... May 2024Metagenomic sequencing (mNGS) is a promising technique for pathogen detection. However, the use of mNGS in pediatric lung infections is still rarely reported.
OBJECTIVE
Metagenomic sequencing (mNGS) is a promising technique for pathogen detection. However, the use of mNGS in pediatric lung infections is still rarely reported.
METHODS
A total of 59 cases were included between January 2019 and December 2021. To compare the performance of mNGS and routine detection in diagnosing pulmonary infection and identifying pathogenic bacteria.
RESULTS
59 children (33.90%) were infected with Mycoplasma pneumoniae, 15 were infected with adenovirus type 7 (25.42%), 11 were infected with Streptococcus pneumoniae (18.64%), 6 were infected with Staphylococcus aureus (10.17%), 5 were infected with Klebsiella pneumoniae, Acinetobacter baumannii, pertussis, and oral streptococcus (8.47%), 3 were infected with Haemophilus influenzae (5.08%), and 3 were infected with Pseudomonas aeruginosa (5.08%). Among 59 patients, 41 were co-infected with multiple pathogens and 18 were infected with independent pathogens. Mycoplasma pneumoniae infection was most common in 6 out of 18 independent pathogen patients (33%). Among them were 3 cases of type 7 adenovirus, 53 cases of human herpesvirus (16.7%), and 2 cases of pertussis bacillus (11.1%). One case (5.6%) was infected with Streptococcus pneumoniae, Proteus albicans, Mycobacterium tuberculosis, Staphylococcus aureus, and Klebsiella pneumoniae. In cases where routine testing results are negative, mNGS improves the diagnostic efficiency of mixed pulmonary infections. 17 cases (17/59=28.81%) were diagnosed as single infection through routine testing, and the mNGS results of 4 cases were consistent with routine testing, all of which were Mycoplasma pneumoniae infections. Three cases were tested for partial mNGS matching, of which one case tested positive for Mycoplasma pneumoniae antibody and tested positive for Mycoplasma pneumoniae infection and human infection γ Herpes virus type 4, one case tested positive for antibodies and tested for infection with Mycoplasma pneumoniae and Streptococcus pneumoniae. The routine examination results of the remaining 11 patients were inconsistent with the mNGS examination results. Two patients tested positive for Mycoplasma antibodies. Patient 17 presented with mNGS infection of Haemophilus, Neisseria, and adenovirus type 7, while another patient 18 presented with herpes virus type 5 infection.
CONCLUSION
mNGS is a promising technique for detecting co-pathogens in mixed pediatric lung infections, with potential benefits in terms of speed and sensitivity.
PubMed: 38702151
DOI: No ID Found -
The New Microbiologica May 2024The COVID-19 pandemic forced the adoption of non-pharmaceutical interventions (NPIs) which influenced the circulation of other respiratory pathogens, such as Influenza...
The COVID-19 pandemic forced the adoption of non-pharmaceutical interventions (NPIs) which influenced the circulation of other respiratory pathogens, such as Influenza virus (FLU), Parainfluenza virus (PIV), Respiratory Syncytial virus (RSV), Rhinovirus (RV), Enterovirus (EV), Adenovirus (AdV), Human Metapneumovirus (hMPV), and Human Coronavirus (CoV). The aim of the current study was to investigate how, with the end of the pandemic, the withdrawal of the NPIs impacted on the circulation and distribution of common respiratory viruses. The analyzed samples were collected from June 2021 to March 2023 (post-pandemic period) and compared to ones from the pandemic period. Nucleic acid detection of all respiratory viruses was performed by multiplex real time Polymerase Chain Reaction (PCR) and sequencing was conducted by Next Generation Sequencing (NGS) technique. Our analysis shows that the NPIs adopted against SARS-CoV-2 were also effective in controlling the spread of other respiratory viruses. Moreover, we documented how RV/EVs were the most commonly identified species, with the more abundant strains represented by Coxsackievirus (CV)-A/B and RV-A/C. RV/EVs were also detected in some co-infection cases; in particular, the majority of co-infections concerned CV-B/RV-A, CV-B/ECHO. Given the pandemic potential of respiratory viruses, accurate molecular screening is essential for a proper surveillance and prevention strategy.
Topics: Humans; COVID-19; Italy; SARS-CoV-2; Respiratory Tract Infections; Pandemics; Viruses; Adult; Male; Child
PubMed: 38700887
DOI: No ID Found -
Microbes and Infection Apr 2024African swine fever virus (ASFV) infection causes African swine fever (ASF), a highly contagious and fatal disease that poses severe threat to swine production. To gain...
African swine fever virus (ASFV) infection causes African swine fever (ASF), a highly contagious and fatal disease that poses severe threat to swine production. To gain insights into the host responses to ASFV, we generated recombinant adenovirus Ad5 expressing viral membrane proteins p54, p17, and pB117L individually and infected an alveolar cell line, 3D4/21, with these recombinant viruses. Then, the cell lysates were analyzed using label-free quantification proteomic analysis method. A total of 2158 differentially expressed proteins (DEPs) were identified, of which 817, 466, and 875 proteins were from Ad5-p54-, Ad5-p17-, Ad5-pB117L-infected 3D4/21 cells, respectively. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed distinct yet interconnecting patterns of protein interaction networks. Specifically, the Ad5-p54 virus infection enriched the DEPs primarily involved in the metabolic pathways, endocytosis, adherens junction, and SNARE interactions in vesicular transport. The Ad5-p17 virus infection enriched the DEPs in endocytosis, ubiquitin-mediated proteolysis, N-Glycan biosynthesis, and apoptosis, while the Ad5-pB117L virus infection enriched the DEPs in metabolic pathways, endocytosis, oxidative phosphorylation, and focal adhesion. In summary, these results provide a comprehensive proteinomics analysis of the cellular responses to three ASFV membrane proteins, thus facilitating our understanding of ASFV pathogenesis.
PubMed: 38697277
DOI: 10.1016/j.micinf.2024.105348