Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Epitope-based therapeutic targets in HCV genotype 1 non-structural proteins: a novel strategy to combat emerging drug resistance.","authors":"Mireayi Tudi, Adili Sawuti, Maimaitituerhong Abudurusuli, Chao Wu, Xiaoyu Chen, Gulimire Ailimu, Kuerbannisa Wulayin, Maimaitiaili Tuerxun","doi":"10.3389/fcimb.2024.1480987","DOIUrl":"10.3389/fcimb.2024.1480987","url":null,"abstract":"<p><strong>Introduction: </strong>The hepatitis C virus (HCV) poses a major global health challenge, with its non-structural proteins being essential for viral replication and pathogenesis. Mutations in these proteins significantly contribute to drug resistance, necessitating innovative therapeutic strategies. This study aims to identify epitope-based therapeutic targets in the non-structural proteins of HCV genotype 1, employing in-depth in silico tools to counteract emerging drug resistance.</p><p><strong>Methods: </strong>We retrieved approximately 250 sequences of each non-structural protein from the NCBI database, capturing a broad spectrum of variability and sequence alignments, variability analysis and physicochemical property analysis were conducted. We utilized the TEPITOOL server by IEDB to predict cytotoxic T lymphocyte (CTL) epitopes. Following this, we assessed the efficiency of TAP transport and proteasomal cleavage using IEDB's combined predictor tool. The epitopes were selected based on conservancy analysis, immunogenicity, allergenicity, and presence in non-glycosylated regions, ensuring high predictive scores and suitability as vaccine candidates. Epitopes were docked with the HLA-A*02:01 allele and Toll-like receptor-3 using the ClusPro server. The immune response potential of the epitopes was evaluated through <i>in-silico</i> immune stimulation.</p><p><strong>Results: </strong>The study identified 27 potential CTL epitopes from the non-structural proteins, including NS3, NS4a, NS4b, NS5a, and NS5b. Out of these, three lead epitopes demonstrated high conservation (>90%), strong binding affinities to HLA-A*02:01 and TLR-3, and robust immune response potential. These epitopes also showed favorable characteristics such as being non-allergenic and non-glycosylated.</p><p><strong>Conclusion: </strong>This comprehensive <i>in-silico</i> analysis provides a promising foundation for developing an epitope-based vaccine targeting HCV non-structural proteins, offering a novel approach to overcoming drug resistance in HCV treatment.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1480987"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic evaluation of therapeutic effectiveness of Azvudine in treating COVID-19 hospitalized patients: a retrospective cohort study.","authors":"Yingkai Xu, Yuan Huang, Zihan Yuan, Wanbing Liu, Li Wang, Lei Liu","doi":"10.3389/fcimb.2024.1453234","DOIUrl":"10.3389/fcimb.2024.1453234","url":null,"abstract":"<p><strong>Background: </strong>Azvudine, a repurposed oral small molecule antiviral drug, has potential effects in combating the SARS-CoV-2 virus. However, studies on its clinical efficacy in patients with COVID-19 are still limited and controversial, and further research and validation are necessary.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command from 1 December 2022 to 31 January 2023. We included 132 patients treated with Azvudine and 132 controls after screening and propensity score matching. The primary outcomes including all-cause mortality and a composite outcome of disease progression such as non-invasive respiratory support, invasive respiratory support, admission to intensive care unit (ICU), and death were compared.</p><p><strong>Results: </strong>Azvudine recipients had a much lower incidence rate of composite disease progression outcome than controls (13.9075/1000 person-days versus 25.7731/1000 person-days, <i>P</i><0.05). Azvudine recipients also possessed a lower all-cause mortality rate than controls (2.6797/1000 person-days versus 8.5910/1000 person-days, <i>P</i><0.01). Azvudine treatment significantly reduced the risk of composite disease progression (HR: 0.37, 95% CI: 0.16-0.84, <i>P</i>=0.017) and all-cause death (HR: 0.25, 95% CI: 0.08-0.81, <i>P</i>=0.021) after adjusting potential confounding factors such as age, sex, severity of COVID-19, complications, concomitant therapy, time from symptoms to treatment, and important laboratory indicators. The subgroup analyses of composite disease progression outcome and all-cause death indicated robustness of Azvudine's in treating COVID-19 patients in general.</p><p><strong>Conclusion: </strong>Our study demonstrates that Azvudine has a significant positive impact on the clinical recovery of hospitalized patients with COVID-19. These findings provide important support for the use of Azvudine as a therapeutic option for COVID-19, given the current divergent views on its therapeutic efficacy and its importance in public health and medical care.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1453234"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron transport pathways in the human malaria parasite <i>Plasmodium falciparum</i> revealed by RNA-sequencing.","authors":"Juliane Wunderlich, Vadim Kotov, Lasse Votborg-Novél, Christina Ntalla, Maria Geffken, Sven Peine, Silvia Portugal, Jan Strauss","doi":"10.3389/fcimb.2024.1480076","DOIUrl":"10.3389/fcimb.2024.1480076","url":null,"abstract":"<p><p>Host iron deficiency is protective against severe malaria as the human malaria parasite <i>Plasmodium falciparum</i> depends on bioavailable iron from its host to proliferate. The essential pathways of iron acquisition, storage, export, and detoxification in the parasite differ from those in humans, as orthologs of the mammalian transferrin receptor, ferritin, or ferroportin, and a functional heme oxygenase are absent in <i>P. falciparum</i>. Thus, the proteins involved in these processes may be excellent targets for therapeutic development, yet remain largely unknown. Here, we show that parasites cultured in erythrocytes from an iron-deficient donor displayed significantly reduced growth rates compared to those grown in red blood cells from healthy controls. Sequencing of parasite RNA revealed diminished expression of genes involved in overall metabolism, hemoglobin digestion, and metabolite transport under low-iron versus control conditions. Supplementation with hepcidin, a specific ferroportin inhibitor, resulted in increased labile iron levels in erythrocytes, enhanced parasite replication, and transcriptional upregulation of genes responsible for merozoite motility and host cell invasion. Through endogenous GFP tagging of differentially expressed putative transporter genes followed by confocal live-cell imaging, proliferation assays with knockout and knockdown lines, and protein structure predictions, we identified six proteins that are likely required for ferrous iron transport in <i>P. falciparum</i>. Of these, we localized <i>Pf</i>VIT and <i>Pf</i>ZIPCO to cytoplasmic vesicles, <i>Pf</i>MRS3 to the mitochondrion, and the novel putative iron transporter <i>Pf</i>E140 to the plasma membrane for the first time in <i>P. falciparum</i>. <i>Pf</i>NRAMP/<i>Pf</i>DMT1 and <i>Pf</i>CRT were previously reported to efflux Fe²⁺ from the digestive vacuole. Our data support a new model for parasite iron homeostasis, in which <i>Pf</i>E140 is involved in iron uptake across the plasma membrane, <i>Pf</i>MRS3 ensures non-redundant Fe²⁺ supply to the mitochondrion as the main site of iron utilization, <i>Pf</i>VIT transports excess iron into cytoplasmic vesicles, and <i>Pf</i>ZIPCO exports Fe²⁺ from these organelles in case of iron scarcity. These results provide new insights into the parasite's response to differential iron availability in its environment and into the mechanisms of iron transport in <i>P. falciparum</i> as promising candidate targets for future antimalarial drugs.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1480076"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavior, hormone, and gut microbiota change by YYNS intervention in an OVX mouse model.","authors":"Huajuan Lei, Jian Liu, Juan Deng, Pan Zou, Zixiang Zou, Ziou Li, Honghui Li, Lin Luo, Zhoujin Tan","doi":"10.3389/fcimb.2024.1445741","DOIUrl":"10.3389/fcimb.2024.1445741","url":null,"abstract":"<p><strong>Object: </strong>Perimenopause depression disorder (PDD) is a very common problem in clinical practice and is characterized by depression and autonomic nervous symptoms, including hot flashes, palpitation, and night sweating. In addition, the comorbidity of menopause depression has long been an integral component of the estradiol (E2) shortage. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of endocrine and cerebellar networks. Emerging evidence has shown that the endocrine-brain-gut-microbiota axis plays a key role in the regulation of affective disorders. Yangyin-ningshen formula (YYNS) is a traditional Chinese decoction tailored by Yijintang for menopausal depression intervention. Thus, we hypothesized that the YYNS may be involved in the menopause depression alleviation through the endocrine-brain-gut-microbiota axis.</p><p><strong>Methods: </strong>To verify this, we constructed a bilateral ovariectomy (OVX) mouse model to simulate menopausal-related depression. Subsequently, behavioral tests including the open field test (OFT) and the forced swimming test (FST) were conducted to examine the depression state post-OVX. With YYNS or E2 intervention, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum sex hormones level. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to analyze the microbiome of the colon samples collected from mice in the sham surgery group (CSH), the OVX model group (CMD), the OVX with E2 hormone intervention group (CHM), and the OVX with YYNS intervention group (CYYNS). One week after OVX, CMD, CHM, and CYYNS showed depression in OFT, FST. Three weeks post-OVX, CHM and CYYNS showed a notable relief of depression; CMD shaped the OTUs shrinkage; and OTUs were raised in the sham, CHM, and CYYNS group. The CMD group showed that the abundance of Actinobiota decreased but that of Bacteriodia increased. The relative abundance of the genus varied in each group. Moreover, functional correlation of changes in sex hormone and gut microbes between different groups showed that the PRL level was negatively correlated with <i>Odoribacter</i>. T level was positively correlated with <i>Lachnospiraceae NK4A136 group</i> and <i>Odoribacter</i> abundance (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Our results not only offer novel insights into the sex hormones and depression with OVX mice but also build an important basis for E2 or YYNS therapeutic efficacy on PDD, which provide for future research on this etiology through the endocrine-brain-gut-microbiota network.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1445741"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Candida</i> spp. colonization: a genotype source found in blood cultures that can become widespread.","authors":"Aina Mesquida, Pablo Martín-Rabadán, Luis Alcalá, Almudena Burillo, Elena Reigadas, Patricia Muñoz, Jesús Guinea, Pilar Escribano","doi":"10.3389/fcimb.2024.1468692","DOIUrl":"10.3389/fcimb.2024.1468692","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Our previous genotyping studies suggest that some anatomical locations act as reservoirs of genotypes that may cause further candidemia, since we found identical genotypes in gastrointestinal tract or catheter tip isolates and blood cultures, in contrast, we did not find blood culture genotypes in vagina samples. We observed that some genotypes can be found in blood cultures more frequently than others, some of them being called widespread genotypes because have been found in unrelated patients admitted to different hospitals. The presence of widespread genotypes may be more frequently found because of their predisposition to cause candidemia. It is unclear whether genotypes colonizing other anatomical sites different from the gastrointestinal tract can also be detected in this way; we studied &lt;i&gt;C. albicans&lt;/i&gt;, &lt;i&gt;C. parapsilosis&lt;/i&gt;, and &lt;i&gt;C. tropicalis&lt;/i&gt; colonizing genotypes to assess what proportion could be found in blood cultures and the proportion of widespread genotypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The isolates (n= 640 &lt;i&gt;Candida&lt;/i&gt; isolates from 323 patients) studied herein were obtained from samples processed at the Clinical Microbiology and Infectious Diseases Department of the Gregorio Marañón Hospital (Madrid, Spain) from July 1, 2016, to June 30, 2019. &lt;i&gt;C. albicans&lt;/i&gt; (n=486), &lt;i&gt;C. parapsilosis&lt;/i&gt; (n=94), and &lt;i&gt;C. tropicalis&lt;/i&gt; (n=60) isolates were genotyped using species-specific microsatellite markers and sourced from blood (n=120) and colonized anatomical sites (n=520; catheter [n=50], lower respiratory tract [n=227], skin/mucosa [n=132], and urinary tract [n=111]). Isolates with identical genotypes were those presenting the same alleles for all markers or with only differences at one locus of a given marker. Identical genotypes were further classified as a match (identical genotype found in different groups of samples from a given patient) or as a cluster (identical genotype found in ≥2 patients). Finally, singletons were genotypes detected once. The genotypes found were then compared with our in-house database containing 587 blood genotypes from patients admitted to the Gregorio Marañón Hospital (2007-2023) to assess the proportion of genotypes found in colonized samples that were also found in blood cultures. Moreover, since some of our in-house database genotypes had been tagged as widespread genotypes, we compared the proportions of widespread genotypes as well as the proportions of matches, clusters, and patients involved in clusters found among exclusively colonizing genotypes, exclusively blood culture genotypes, and both colonizing and blood culture genotypes using a standard binomial method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Intra-patient analysis was conducted exclusively on those patients (n=225; 69.7%) who had ≥2 isolates from a given species; the proportion of patients with matches was lower in exclusively colonized patients than in patients with candidemia and colonizing","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1468692"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strain-level genomic analysis of serotype, genotype and virulence gene composition of group B streptococcus.","authors":"Zhen Zeng, Meng Li, Simin Zhu, Ke Zhang, Yifan Wu, Minzi Zheng, Yang Cao, Zhenyu Huang, Qinping Liao, Lei Zhang","doi":"10.3389/fcimb.2024.1396762","DOIUrl":"10.3389/fcimb.2024.1396762","url":null,"abstract":"<p><strong>Introduction: </strong>GBS (group B streptococcus) is an opportunistic pathogen that can colonize healthy individuals but presents significant challenges in clinical obstetrics and gynecology, as it can cause miscarriage, preterm birth, and invasive infections in newborns. To develop specific and personalized preventative strategies, a better understanding of the epidemiological characteristics and pathogenic features of GBS is essential.</p><p><strong>Methods: </strong>We conducted a comprehensive strain-level genomic analysis of GBS, examining serotype and genotype distributions, as well as the composition and correlations of virulence genes using the blastn-short mode of the BLAST program(v2.10.0+), mlstsoftware (https://github.com/tseemann/mlst), Snippy (v4.6.0), FastTree (v2.1.11) and iTOL. The coding sequence region of virulence factors was annotated by Prodigal (v2.6.3) and Glimmer(v3.02b). We further identified host protein interacting with Srr2 by mass spectrometry analysis.</p><p><strong>Results: </strong>While certain genotypes showed strong serotype consistency, there was no significant association between overall serotypes and genotypes. However, the composition of virulence genes was more closely related to the phylogeny of GBS, among which simultaneous presence of Srr2 and HygA exhibit significant association with hypervirulence. Tubulin emerged as the most distinct and abundant hit. The specific interaction of Tubulin with Srr2-BR, rather than Srr1-BR, was further confirmed by immunoblotting.</p><p><strong>Discussion: </strong>Considering the impact of cytoskeleton rearrangement on GBS pathogenesis, this observation offers a plausible explanation for the hypervirulence triggered by Srr2. Collectively, our findings indicate that in the future clinical practice, virulence gene detection should be given more attention to achieve precise GBS surveillance and disease prevention.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1396762"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides.","authors":"Melisa Gualdrón-López, Alberto Ayllon-Hermida, Núria Cortes-Serra, Patricia Resa-Infante, Joan Josep Bech-Serra, Iris Aparici-Herraiz, Marc Nicolau-Fernandez, Itziar Erkizia, Lucia Gutierrez-Chamorro, Silvia Marfil, Edwards Pradenas, Carlos Ávila Nieto, Bernat Cucurull, Sergio Montaner-Tarbés, Magdalena Muelas, Ruth Sotil, Ester Ballana, Victor Urrea, Lorenzo Fraile, Maria Montoya, Julia Vergara, Joaquim Segales, Jorge Carrillo, Nuria Izquierdo-Useros, Julià Blanco, Carmen Fernandez-Becerra, Carolina de La Torre, Maria-Jesus Pinazo, Javier Martinez-Picado, Hernando A Del Portillo","doi":"10.3389/fcimb.2024.1442743","DOIUrl":"10.3389/fcimb.2024.1442743","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1442743"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical and diverse role of alarmin cytokines in parasitic infections.","authors":"Zhou Xing, Suiyi Liu, Xing He","doi":"10.3389/fcimb.2024.1418500","DOIUrl":"10.3389/fcimb.2024.1418500","url":null,"abstract":"<p><p>Alarmin cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) function as danger signals to trigger host immunity in response to tissue injury caused by pathogenic factors such as parasitic infections. Parasitic diseases also provide an excellent context to study their functions and mechanisms. Numerous studies have indicated that alarmin cytokine released by non-immune cells such as epithelial and stromal cells induce the hosts to initiate a type 2 immunity that drives parasite expulsion but also host pathology such as tissue injury and fibrosis. By contrast, alarmin cytokines especially IL-33 derived from immune cells such as dendritic cells may elicit an immuno-suppressive milieu that promotes host tolerance to parasites. Additionally, the role of alarmin cytokines in parasite infections is reported to depend on species of parasites, cellular source of alarmin cytokines, and immune microenvironment, all of which is relevant to the parasitic sites or organs. This narrative review aims to provide information on the crucial and diverse role of alarmin cytokines in parasitic infections involved in different organs including intestine, lung, liver and brain.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1418500"},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematologic cancers and infections: how to detect infections in advance and determine the type?","authors":"Yan Chen, Tao Ma","doi":"10.3389/fcimb.2024.1476543","DOIUrl":"10.3389/fcimb.2024.1476543","url":null,"abstract":"<p><p>Infection is one of the leading causes of death in patients with hematologic cancers. Hematologic cancer patients with compromised immune systems are already susceptible to infections, which come on even more rapidly and are difficult to control after they develop neutrophil deficiencies from high-dose chemotherapy. After patients have developed an infection, the determination of the type of infection becomes a priority for clinicians. In this review, we summarize the biomarkers currently used for the prediction of infections in patients with hematologic cancers; procalcitonin, CD64, cytokines, and CD14 et al. can be used to determine bacterial infections, and (1-3)-β-D-glucan and galactomannan et al. can be used as a determination of fungal infections. We have also focused on the use of metagenomic next-generation sequencing in infections in patients with hematologic cancers, which has excellent clinical value in infection prediction and can detect microorganisms that cannot be detected by conventional testing methods such as blood cultures. Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient's clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1476543"},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cdc42 improve SARS-CoV-2 spike protein-induced cellular senescence through activating of Wnt/β-Catenin signaling pathway.","authors":"Chunmei Nong, Zhenzhen Wu, Chan Yang, Wei Xu, Linyi Luo, Jianping Zhou, Lihan Shen, Yinghua Chen, Yaoqin Yuan, Guodong Hu","doi":"10.3389/fcimb.2024.1449423","DOIUrl":"10.3389/fcimb.2024.1449423","url":null,"abstract":"<p><strong>Introduction: </strong>SARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. Cdc42 is involved in the regulation of cellular senescence. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence through Cdc42.</p><p><strong>Methods: </strong>K18-hACE2 mice were infected with SARS-CoV-2 Omicron BA.4 or stimulated with spike protein through the airway, the senescent cells and Cdc42 expression in lung tissue were detected. Overexpression of spike protein or exogenous incubation of spike protein was used to simulate the induction of cellular senescence by spike protein. Mechanistic insights into the role of Cdc42 were mainly explored using Western Blot and qRT-PCR.</p><p><strong>Results: </strong>Spike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation.</p><p><strong>Discussion: </strong>This study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1449423"},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}