{"title":"Identification and Functional Analysis of Key Genes Involved in Community-Acquired Pneumonia Inflammation Based on Bioinformatics","authors":"Chao Li, Zhidan Hua, Xiaoling Wang, Suqin Wen, Jianhui Sheng","doi":"10.1111/1348-0421.70010","DOIUrl":"10.1111/1348-0421.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Previous studies have revealed various treatment modalities for community-acquired pneumonia (CAP), but there is still a lack of in-depth research on inflammation-related genes (IRGs) in CAP. In this analysis, we collected clinical data from CAP patients and identified CAP differentially expressed IRGs (CAP-DE-IRGs) between healthy individuals and CAP patients. Subsequently, functional and pathway enrichment analyses were carried out on CAP-DE-IRGs. Furthermore, hub genes in IRGs were identified, with their diagnostic ability and function validated. Enrichment analyses demonstrated that these CAP-DE-IRGs were abundant in biological processes such as cytokine-cytokine receptor interaction and JAK-STAT signaling pathway. Five hub genes were selected from IRGs. Quantitative Real-time PCR (qRT-PCR) results showed that CCL5, IL7R, IL2RB, and IL10RA were significantly downregulated in CAP patients, and IL18R1 was significantly upregulated in CAP patients (<i>p</i> < 0.05). In the validation of the diagnostic ability of hub genes, most of the genes exhibited area under curve (AUC) values exceeding 0.7, indicating the excellent diagnostic ability of hub genes. The function prediction of hub genes unraveled that hub genes had the functions of cytokine receptor binding, immune receptor activity, response to interleukin-7, and so on. The immune infiltration analysis demonstrated that immune cell Neutrophils exhibited higher infiltration in CAP patients than in healthy individuals. The correlation analysis of hub genes and CAP-related genes manifested that the hub gene IL18R1 was positively correlated with CAP-related genes. In summary, our analysis identified a connection between CAP patients and IRGs, which is beneficial for further research on CAP.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 11","pages":"562-574"},"PeriodicalIF":1.8,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enterotoxigenic Escherichia coli Vaccine Candidate MecVax With Protein Antigens Prepared From Animal-Free Media Is Equally Immunogenic and Protective Against Adhesins CFA/I, CS1–CS6 and Toxins LT and STa","authors":"Ipshita Upadhyay, Bedaso Edao, Weiping Zhang","doi":"10.1111/1348-0421.70008","DOIUrl":"10.1111/1348-0421.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Enterotoxigenic <i>Escherichia coli</i> (ETEC) is a leading cause of diarrhea in young children in low- and middle-income countries and the most common cause of diarrhea in international travelers. Currently, there are no vaccines licensed to prevent ETEC-associated diarrhea. MecVax, a protein-based, multivalent ETEC vaccine candidate, has been demonstrated to be broadly immunogenic and cross-protective in preclinical studies. However, the two recombinant proteins of MecVax were prepared from 2× Yeast Extract Tryptone medium (2× YT, which contains animal materials) and are therefore unsuitable for a human vaccine. In this study, we prepared MecVax recombinant proteins using two animal material-free media (Terrific Broth Complete with animal-free Soytone and 2× YT with animal-free Soytone) and comparatively evaluated the vaccine products for immunogenicity and antibody functions against ETEC bacterial adherence and toxin enterotoxicity. Data showed that MecVax protein antigens prepared from a culture medium without or with animal materials showed no differences in protein yield, reactivity with specific antibodies, and induction of antigen-specific IgG responses in mice. Moreover, the mouse serum antibodies exhibited the same level of inhibition of adherence from ETEC bacteria expressing CFA/I, CS1–CS6, as well as neutralization of ETEC heat-stable toxin or heat-labile toxin. These results indicate that MecVax can be prepared using an animal-free Soytone medium, thereby accelerating the development of this vaccine product against ETEC-associated diarrhea in children and travelers. Additionally, we conducted an additional MecVax dosage study in mouse immunization and refined the minimum effective dose to 2 μg of each protein antigen.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 11","pages":"553-561"},"PeriodicalIF":1.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-186 Regulates Septic Hyperinflammation and Predicts Sepsis","authors":"Xiangru Li, Hongyan Cai, Boyuan Wang, Weiwei Luo, Rui Jia, Shaoyan Si, Mei Hu, Xiaotong Lou","doi":"10.1111/1348-0421.70007","DOIUrl":"10.1111/1348-0421.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is a life-threatening condition caused by infection-induced immune dysregulation. Clinically distinguishing sepsis from infection remains to be a challenge due to overlapping clinical features. Although miR-186 regulates cell proliferation and apoptosis, and was predicted to target immune-related genes, its role in sepsis is unclear. We retrospectively enrolled 21 infected patients and 20 sepsis patients. The miR-186 level in blood cells was detected using real-time PCR. Cytokine concentrations and lymphocyte subpopulation proportions were determined using flow cytometry. Clinical data were retrieved from medical records. The diagnostic ability of miR-186 was compared with procalcitonin and lactate using the receiver operating characteristic (ROC) curve. miR-186 was inhibited in human umbilical vein endothelial cells (HUVECs) and mice, followed by measurement of cytokine expression using real-time PCR and flow cytometry. The expression level of miR-186 was significantly higher in septic patients than in infected patients. miR-186 showed relatively better diagnostic performance for sepsis than procalcitonin and lactate. The in vitro assay showed that LPS enhanced miR-186 expression under a dose-dependent manner. In vitro miR-186 inhibition in HUVECs inhibited <i>IL-1β</i>, <i>IL-6</i>, and <i>IL-8</i> expression. In vivo miR-186 inhibition significantly lowered IL-1β concentration and natural killer cell ratio. In this study, we found that miR-186 is significantly upregulated in sepsis and plays a regulatory role in cytokine expression, highlighting its potential as a diagnostic biomarker for sepsis.</p></div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"522-531"},"PeriodicalIF":1.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening and Characterization of B-Cell Epitopes of Porcine Respiratory Coronavirus Receptor Binding Domain Using Monoclonal Antibodies","authors":"Aiping Wang, Jiachen Wang, Jingming Zhou, Yumei Chen, Hongliang Liu, Chao Liang, Xifang Zhu, Enping Liu, Sixuan Wu, Yanhua Qi, Gaiping Zhang","doi":"10.1111/1348-0421.70002","DOIUrl":"10.1111/1348-0421.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>The spike (S) glycoprotein of porcine respiratory coronavirus (PRCV) plays a critical role in viral entry, with its receptor binding domain (RBD) on the S1 subunit responsible for interacting with the host receptor porcine aminopeptidase N. In this study, the PRCV RBD protein was successfully expressed, and a monoclonal antibody (mAb), 2E6, was produced using hybridoma technology. The specificity of 2E6 was confirmed by western blot and indirect immunofluorescence assay (IFA). To identify the linear B-cell epitope recognized by 2E6, the RBD was initially divided into three overlapping fragments, cloned into pET-32a vectors, and expressed in <i>Escherichia coli</i> BL21 (DE3). Dot blot analysis revealed that 2E6 reacted with the RBD-1 fragment (amino acids 299–357). Further subdivision into RBD1-1, RBD1-2, and RBD1-3, followed by expression using both pET-32a and pEGFP-C1 vectors, enabled Dot blot and IFA validation of specific recognition of RBD1–3 (amino acids 329–347). Subsequent peptide mapping using synthetic overlapping peptides (RBD-P1, P2, P3) confirmed that the minimal linear epitope lies within RBD-P2 (amino acids 334–343). This epitope is surface-exposed and conserved among PRCV strains, making it a promising candidate for diagnostic assay development and epitope-based vaccine design.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"477-485"},"PeriodicalIF":1.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroki Kondo, Juri Koizumi, Keita Takahashi, Tetsuo Koshizuka
{"title":"Evaluation of the Antiherpes Simplex Virus Activities of Thiourea-Based Compounds","authors":"Hiroki Kondo, Juri Koizumi, Keita Takahashi, Tetsuo Koshizuka","doi":"10.1111/1348-0421.70005","DOIUrl":"10.1111/1348-0421.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>The emergence of drug-resistant viruses, particularly in immunocompromised individuals, has necessitated the development of novel antiviral drugs. We previously identified compound 147B3 as an inhibitor of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). Although 147B3 exhibits cytotoxicity, it inhibits the function of infected cell protein 4 (ICP4), a viral transcription factor essential for HSV-1 replication. In this study, we evaluated five commercially available compounds (1C6, 1C6L, 1H6, 1H6L, and 2D10) that had structural similarity to 147B3, exhibited potent anti-HSV-1 activity with reduced cytotoxicity. Among these, 1C6L and 1H6L are structural analogs of 1C6 and 1H6, respectively. An HSV-1 strain resistant to 147B3 carrying a mutation in ICP4 exhibited resistance to all the five compounds, suggesting a shared mechanism of action involving ICP4. Among these compounds, 1H6L had the highest selective index against HSV-1. Notably, these compounds did not reduce early or late protein expression of HSV-1, unlike the parent compound 147B3. Although viral genome replication occurred in the presence of 1H6L, it prevented virion release into the culture supernatant. The cell fraction analysis revealed that 1H6L reduced the size of the cytoplasmic HSV-1 genome. These findings suggest that 1H6L shares certain aspects of its mechanism of action with the parent compound 147B3 but may also inhibit multiple steps in the HSV-1 life cycle.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"511-521"},"PeriodicalIF":1.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aila Gulijiahani, Vuk Isakovic, Yasuko Mori, Jun Arii
{"title":"Comparative Analysis of the Nuclear Egress Complex in Human Herpesvirus 6A and 6B","authors":"Aila Gulijiahani, Vuk Isakovic, Yasuko Mori, Jun Arii","doi":"10.1111/1348-0421.70004","DOIUrl":"10.1111/1348-0421.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Herpesvirus nucleocapsids are transported from the nucleus to the cytoplasm via a conserved process known as nuclear egress, which is mediated by the nuclear egress complex (NEC) consisting of two core viral proteins. Although the NEC structure is conserved among herpesviruses, functional divergence may exist. Human herpesvirus 6A (HHV-6A) and HHV-6B are genetically similar members of the <i>Roseolovirus</i> genus within the <i>Betaherpesvirinae</i> subfamily, yet they differ in their pathogenic profiles. In this study, we examined and compared the functions of NEC components U37 and U34 from HHV-6A and HHV-6B. We demonstrated that HHV-6A U34 localizes to the nuclear envelope via its C-terminal transmembrane domain and is essential for viral replication. Moreover, NEC components from HHV-6A and HHV-6B colocalize at the nuclear rim and share a high degree of sequence similarity. These findings suggest that the nuclear egress mechanism is highly conserved within roseoloviruses, despite their distinct biological properties.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"502-510"},"PeriodicalIF":1.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karin C. Garcia, Samuel N. Santos, Bruna R. Flose, Maria A. Juliano, Renan B. Domingues, Lucas M. Neves, Guilherme José Costa Silva, Liã B. Arruda, Augusto C. Penalva-de-Oliveira, Sandro L. de Andrade Matas, Marina T. Shio, Luiz H. da Silva Nali
{"title":"Anti-Human Endogenous Retrovirus and Anti-Myelin Oligodendrocyte Glycoprotein Humoral Response in Cerebrospinal Fluid of Multiple Sclerosis Patients: A Case Control Study","authors":"Karin C. Garcia, Samuel N. Santos, Bruna R. Flose, Maria A. Juliano, Renan B. Domingues, Lucas M. Neves, Guilherme José Costa Silva, Liã B. Arruda, Augusto C. Penalva-de-Oliveira, Sandro L. de Andrade Matas, Marina T. Shio, Luiz H. da Silva Nali","doi":"10.1111/1348-0421.70003","DOIUrl":"10.1111/1348-0421.70003","url":null,"abstract":"<p>It is believed that human endogenous retrovirus (HERV)-W plays a fundamental role in multiple sclerosis (MS) pathogenesis, probably by inducing humoral and cellular immunopathological response. HERVs present regions of similarity to myelin oligodendrocyte glycoprotein (MOG) and therefore could induce autoimmunity through the mechanism of molecular mimicry via cross-humoral response. This study aimed to evaluate the impact of HERV-mediated humoral response among MS patients by assessing IgG antibody levels of HERV-W and K in cerebrospinal fluid (CSF). CSF samples were collected from MS patients (<i>n</i> = 25) and idiopathic intracranial hypertension (IIH) patients (<i>n</i> = 25). Serum samples from MS group (<i>n</i> = 25) were also analyzed. CSF samples were assessed for global and differential cell counts, analytical biochemistry, and oligoclonal bands analysis. ELISA was used to determine the serum and intrathecal (CSF) presence and concentration of anti-MOG, anti-HERV-W-env, and anti-HERV-K-pol antibodies. ELISA findings revealed higher concentrations of anti-MOG and HERV-W IgG in MS compared to IIH (<i>p</i> < 0.01 and <i>p</i> = 0.0142 respectively), while HERV-K IgG showed concentration to three HERV-K peptides (<i>p</i> < 0.01). A positive correlation was also observed between serum and CSF antibody concentration for MOG (<i>r</i> = 0.47 <i>p</i> = 0.01), HERV-W (<i>r</i> = 0.72 <i>p</i> < 0.01), and three HERV-K peptides (<i>r</i> = 0.49, 0.57, 0.61 and <i>p</i> = 0.0126, <i>p</i> < 0.01, and <i>p</i> < 0.01, respectively) among MS patients. Our findings revealed high concentrations of anti-HERV-K and -W antibodies in serum and CSF among MS patients, suggesting a possible role of humoral immunopathological response. In addition, the positive correlation between serum and CSF antibody concentration indicates the potential application of serum levels of anti-HERV and anti-MOG as biomarkers for MS.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"495-501"},"PeriodicalIF":1.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Potential of Lactobacillus plantarum ATG-K2 in Bacterial Vaginosis: In Vitro and In Vivo Evidence","authors":"Yeon-Hwa Park, Juyi Park, Ye-Won Kang, Jihee Kang","doi":"10.1111/1348-0421.70001","DOIUrl":"10.1111/1348-0421.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>Bacterial vaginosis (BV) is characterized by reduced vaginal lactobacilli and pathogenic bacteria proliferation, leading to symptoms such as vaginal epithelial cell detachment and unpleasant odor, along with various complications. Most <i>Lactobacillus</i> species play a crucial role in not only inhibiting BV, but also maintaining vaginal health. We aimed to determine whether <i>Lactobacillus plantarum</i> ATG-K2 has therapeutic and preventive effects against <i>Gardnerella vaginalis</i> (GV), a representative pathogen of BV. In vitro cell assays confirmed that ATG-K2 clusters within cells without cytotoxic effects and inhibits both the cytotoxicity and GV adhesion. Furthermore, biofilm formation assays using crystal violet revealed that ATG-K2 disrupts GV-formed biofilms. In GV-induced BV mouse models, ATG-K2 reduced clue cell formation and sialidase activity, thereby addressing the key aspects of BV. Additionally, when ATG-K2 was administered, the measurement of GV DNA within the vaginal tissue revealed a reduction in GV. In conclusion, ATG-K2 holds promise as a therapeutic agent for BV by inhibiting GV colonization and the associated pathology, potentially offering an alternative to antibiotics.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"457-465"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}