Pathogenesis Of Infection Research Articles

Evolutionary dynamics of the accessory genomes of Staphylococcus aureus.

Staphylococcus aureus is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant S. aureus. S. aureus is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of S. aureus, we aim to determine how the accessory genome content among phylogenetic lineages of S. aureus is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in S. aureus that are structured by the history of the specific lineages that carry them.IMPORTANCEStaphylococcus aureus is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within S. aureus. Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of S. aureus as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.

LACONICALLY REVIEWED CONCEPTS PERTAINING THE ROTAVIRUS: A SEVERE DIARRHEA CAUSING MICROBE

Nigeria and developing countries are suffering from infectious diseases due to a mixture of determinants. Parable, rotavirus is a major concern that causes a lot of deaths and hospitalization among children under five of age. Therefore, it is imperative to have more understanding of the rotavirus. A literature review to form concepts were made under the following headings: Historical background of the Rotaviruses, General Characteristics of Rotaviruses, Classification of Rotaviruses, Structure of Rotavirus particle, Rotavirus protein, Non- structural proteins, Structure of Rotavirus genome, Genetic reassortment of Rotaviruses, Mechanisms of Rotavirus genetic diversity, Rotavirus infection, Rotavirus replication, Transmission of Rotaviruses, Incubation period of Rotaviruses, Pathogenesis of Rotavirus infection, Signs and symptoms of Rotavirus infection, Immunity to Rotaviruses, Laboratory diagnosis of Rotaviruses, Epidemiology of Rotaviruses, Treatment of rotavirus infection, Antiviral therapy, Other Therapies, Management of Rotavirus infection, Prevention of Rotavirus infections, General Preventive Measures, Hospital Infection Control Measures. This information would invariably help in gaining understanding the basics of Rotavirus that causes diarrhea in children.

Pathogenesis and clinical forms of human listeriosis

Listeriosis is a saprozoonotic infection caused in humans mainly by the species Listeria monocytogenes. Its source can be objects of the external environment (soil and water of open reservoirs with a high content of organic compounds, plants) and more than 90 species of animals. The high metabolic activity of listeria and resistance to adverse factors create the possibility of an easy transition from a saprophytic to a parasitic type of metabolism when ingested by the host. A variety of transmission routes and "entrance gates" cause the emergence of a variety of primary localized forms of infection, the most common of which is gastrointestinal. Invasive forms of listeriosis develop mainly in people with immunological insufficiency. "Risk groups" are pregnant women, newborns, people with comorbid conditions, over 60 years old, drug addicts, etc. They are characterized by polymorphism of symptoms, the absence of specific manifestations. Pathogenicity factors of L. are important in the pathogenesis of infection. monocytogenes, providing their incomplete phagocytosis, intracellular parasitism, high rate of colonization of neighboring healthy cells, the formation of antibiotic resistance. The pathological expression of changes caused by listeria in cells is the formation of small granulomas — listeriomas. The "diversity" of listeriosis, the high mortality rate (up to 50% or more) and the low alertness of doctors regarding this infection create difficulties in making a diagnosis, and therefore the improvement of microbiological diagnostic methods is of particular importance.

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge.

Glaesserella parasuis (G. parasuis) causes systemic infection in pigs, but its effects on skeletal muscle and underlying mechanisms are poorly understood. We investigated G. parasuis infection in colostrum-deprived piglets, observing decreased daily weight gain and upregulation of inflammatory factors in skeletal muscle. Muscle fiber area and diameter were significantly reduced in the treated group (n = 3) compared to the control group (n = 3), accompanied by increased expression of FOXO1, FBXO32, TRIM63, CTSL, and BNIP3. Based on mRNA and microRNA (miRNA) sequencing, we identified 1642 differentially expressed (DE) mRNAs and 19 known DE miRNAs in skeletal muscle tissues between the two groups. We predicted target genes with opposite expression patterns to the 19 miRNAs and found significant enrichment and activation of the FoxO signaling pathway. We found that the upregulated core effectors FOXO1 and FOXO4 were targeted by downregulated ssc-miR-486, ssc-miR-370, ssc-miR-615, and ssc-miR-224. Further investigation showed that their downstream upregulated genes involved in protein degradation were also targeted by the downregulated ssc-miR-370, ssc-miR-615, ssc-miR-194a-5p, and ssc-miR-194b-5p. These findings suggest that G. parasuis infection causes skeletal muscle atrophy in piglets through accelerated protein degradation mediated by the "miRNAs-FOXO1/4" axis, while further research is necessary to validate the regulatory relationships. Our results provide new insights into the understanding of systemic inflammation growth mechanisms caused by G. parasuis and the role of miRNAs in bacterial infection pathogenesis.

The ecto-enzyme CD38 modulates CD4T cell immunometabolic responses and participates in HIV pathogenesis.

Despite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after T cell receptor (TCR)-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular nicotinamide adenine dinucleotide and nicotinamide mononucleotide concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the oxygen consumption rate/extracellular acidification rate ratio upon TCR signaling and to increase cycling, proliferation, survival, and CD40L induction. Pharmacological inhibition of ecto-CD38 catalytic activity in TM cells from chronic HIV-infected patients rescued TCR-triggered responses, including differentiation and effector functions, while reverting abnormally increased basal glycolysis, cycling, and spontaneous proinflammatory cytokine production. Additionally, ecto-CD38 blockage normalized basal and TCR-induced mitochondrial morphofunctionality, while increasing respiratory capacity in cells from HIV+ patients and healthy individuals. Ectoenzyme CD38's immunometabolic restriction of TCR-involving stimulation is relevant to CD4T cell biology and to the deleterious effects of CD38 overexpression in HIV disease.

Mycobacterium tuberculosis-dependent monocyte expression quantitative trait loci, cytokine production, and TB pathogenesis.

The heterogeneity of outcomes after Mycobacterium tuberculosis (Mtb) exposure is a conundrum associated with millennia of host-pathogen co-evolution. We hypothesized that human myeloid cells contain genetically encoded, Mtb-specific responses that regulate critical steps in tuberculosis (TB) pathogenesis. We mapped genome-wide expression quantitative trait loci (eQTLs) in Mtb-infected monocytes with RNAseq from 80 Ugandan household contacts of pulmonary TB cases to identify monocyte-specific, Mtb-dependent eQTLs and their association with cytokine expression and clinical resistance to tuberculin skin test (TST) and interferon-γ release assay (IGRA) conversion. cis-eQTLs (n=1,567) were identified in Mtb-infected monocytes (FDR<0.01), including 29 eQTLs in 16 genes which were Mtb-dependent (significant for Mtb:genotype interaction [FDR<0.1], but not classified as eQTL in uninfected condition [FDR≥0.01]). A subset of eQTLs were associated with Mtb-induced cytokine expression (n=8) and/or clinical resistance to TST/IGRA conversion (n=1). Expression of BMP6, an Mtb-dependent eQTL gene, was associated with IFNB1 induction in Mtb-infected and DNA ligand-induced cells. Network and enrichment analyses identified fatty acid metabolism as a pathway associated with eQTL genes. These findings suggest that monocyte genes contain Mtb-dependent eQTLs, including a subset associated with cytokine expression and/or clinical resistance to TST/IGRA conversion, providing insight into immunogenetic pathways regulating susceptibility to Mtb infection and TB pathogenesis.

Engagement of α3β1 and α2β1 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes.

The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3β1 and α2β1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3β1 and anti-α2β1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3β1 and α2β1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3β1 and α2β1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.

A comprehensive review of monkeypox virus and mpox characteristics.

Monkeypox virus (MPXV) is the etiological agent of monkeypox (mpox), a zoonotic disease. MPXV is endemic in the forested regions of West and Central Africa, but the virus has recently spread globally, causing outbreaks in multiple non-endemic countries. In this paper, we review the characteristics of the virus, including its ecology, genomics, infection biology, and evolution. We estimate by phylogenomic molecular clock that the B.1 lineage responsible for the 2022 mpox outbreaks has been in circulation since 2016. We interrogate the host-virus interactions that modulate the virus infection biology, signal transduction, pathogenesis, and host immune responses. We highlight the changing pathophysiology and epidemiology of MPXV and summarize recent advances in the prevention and treatment of mpox. In addition, this review identifies knowledge gaps with respect to the virus and the disease, suggests future research directions to address the knowledge gaps, and proposes a One Health approach as an effective strategy to prevent current and future epidemics of mpox.

Design, synthesis, biological evaluation and docking study of some new aryl and heteroaryl thiomannosides as FimH antagonists

FimH is a mannose-recognizing lectin that is expressed by Escherichia coli guiding its ability to adhere and infect cells. It is involved in pathogenesis of urinary tract infections and Chron’s disease. Several X-ray structure-guided ligand design studies were extensively utilized in the discovery and optimization of small molecule aryl mannoside FimH antagonists. These antagonists retain key specific interactions of the mannose scaffolds with the FimH carbohydrate recognition domains. Thiomannosides are attractive and stable scaffolds, and this work reports the synthesis of some of their new aryl and heteroaryl derivatives as FimH antagonists. FimH-competitive binding assays as well as biofilm inhibition of the new compounds (24–32) were determined in comparison with the reference n-heptyl α-d-mannopyranoside (HM). The affinity among these compounds was found to be governed by the structure of the aryl and heteroarylf aglycones. Two compounds 31 and 32 revealed higher activity than HM. Molecular docking and total hydrophobic to topological polar surface area ratio calculations attributed to explain the obtained biological results. Finally, the SAR study suggested that introducing an aryl or heteroaryl aglycone of sufficient hydrophobicity and of proper orientation within the tyrosine binding site considerably enhance binding affinity. The potent and synthetically feasible FimH antagonists described herein hold potential as leads for the development of sensors for detection of E. coli and treatment of its diseases.

Antagonizing roles of SHP1 in the pathogenesis of Helicobacterpylori infection.

SHP1 has been documented as a tumor suppressor and it was thought to play an antagonistic role in the pathogenesis of Helicobacter pylori infection. In this study, the exact mechanism of this antagonistic action was studied. AGS, MGC803, and GES-1 cells were infected with H. pylori, intracellular distribution changes of SHP1 were first detected by immunofluorescence. SHP1 overexpression and knockdown were then constructed in these cells to investigate its antagonistic roles in H. pylori infection. Migration and invasion of infected cells were detected by transwell assay, secretion of IL-8 was examined via ELISA, the cells with hummingbird-like alteration were determined by microexamination, and activation of JAK2/STAT3, PI3K/Akt, and ERK pathways were detected by immunoblotting. Mice infection model was established and gastric pathological changes were evaluated. Finally, the SHP1 activator sorafenib was used to analyze the attenuating effect of SHP1 activation on H. pylori pathogenesis invitro and invivo. The sub-localization of SHP1 changed after H. pylori infection, specifically that the majority of the cytoplasmic SHP1 was transferred to the cell membrane. SHP1 inhibited H. pylori-induced activation of JAK2/STAT3 pathway, PI3K/Akt pathway, nuclear translocation of NF-κB, and then reduced EMT, migration, invasion, and IL-8 secretion. In addition, SHP1 inhibited the formation of CagA-SHP2 complex by dephosphorylating phosphorylated CagA, reduced ERK phosphorylation and the formation of CagA-dependent hummingbird-like cells. In the mice infection model, gastric pathological changes were observed and increased IL-8 secretion, indicators of cell proliferation and EMT progression were also detected. By activating SHP1 with sorafenib, a significant curative effect against H. pylori infection was obtained invitro and invivo. SHP1 plays an antagonistic role in H. pylori pathogenesis by inhibiting JAK2/STAT3 and PI3K/Akt pathways, NF-κB nuclear translocation, and CagA phosphorylation, thereby reducing cell EMT, migration, invasion, IL-8 secretion, and hummingbird-like changes.

Genetic evidence strengthens the bidirectional connection between gut microbiota and Shigella infection: insights from a two-sample Mendelian randomization study.

In recent investigations, substantial strides have been made in the precise modulation of the gut microbiota to prevent and treat a myriad of diseases. Simultaneously, the pressing issue of widespread antibiotic resistance and multidrug resistance resulting from Shigella infections demands urgent attention. Several studies suggest that the antagonistic influence of the gut microbiota could serve as a novel avenue for impeding the colonization of pathogenic microorganisms or treating Shigella infections. However, conventional research methodologies encounter inherent challenges in identifying antagonistic microbial agents against Shigella, necessitating a comprehensive and in-depth analysis of the causal relationship between Shigella infections and the gut microbiota. Utilizing the aggregated summary statistics from Genome-Wide Association Studies (GWAS), we conducted Mendelian Randomization (MR) analyses encompassing 18,340 participants to explore the interplay between the gut microbiota and Shigella infections. This investigation also involved 83 cases of Shigella infection patients and 336,396 control subjects. In the positive strand of our findings, we initially performed a preliminary analysis using the Inverse Variance Weighting (IVW) method. Subsequently, we undertook sensitivity analyses to assess the robustness of the results, addressing confounding factors' influence. This involved employing the Leave-One-Out method and scrutinizing funnel plots to ensure the reliability of the MR analysis outcomes. Conclusively, a reverse MR analysis was carried out, employing the Wald ratio method due to the exposure of individual Single Nucleotide Polymorphisms (SNPs). This was undertaken to explore the plausible associations between Shigella infections and genetically predicted compositions of the gut microbiota. In this study, we employed 2,818 SNPs associated with 211 species of gut microbiota as instrumental variables (IVs). Through IVW analysis, our positive MR findings revealed a significant negative correlation between the occurrence of Shigella infections and the phylum Tenericutes (OR: 0.18, 95% CI: 0.04-0.74, p = 0.02), class Mollicutes (OR: 0.18, 95% CI: 0.04-0.74, p = 0.02), genus Intestinimonas (OR: 0.16, 95% CI: 0.04-0.63, p = 0.01), genus Gordonibacter (OR: 0.39, 95% CI: 0.16-0.93, p = 0.03), and genus Butyrivibrio (OR: 0.44, 95% CI: 0.23-0.87, p = 0.02). Conversely, a positive correlation was observed between the occurrence of Shigella infections and genus Sutterella (OR: 10.16, 95% CI: 1.87-55.13, p = 0.01) and genus Alistipes (OR: 12.24, 95% CI: 1.71-87.34, p = 0.01). In sensitivity analyses, utilizing MR-Egger regression analysis and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) detection, all outcomes demonstrated robust stability. Simultaneously, in the reverse MR analysis, Shigella infections resulted in an upregulation of four bacterial genera and a downregulation of three bacterial genera. In summation, the MR analysis outcomes corroborate the presence of bidirectional causal relationships between the gut microbiota and Shigella infections. This study not only unveils novel perspectives for the prevention and treatment of Shigella infections but also furnishes fresh insights into the mechanistic underpinnings of how the gut microbiota contributes to the pathogenesis of Shigella infections. Consequently, the established dual causal association holds promise for advancing our understanding and addressing the complexities inherent in the interplay between the gut microbiota and Shigella infections, thereby paving the way for innovative therapeutic interventions and preventive strategies in the realm of Shigella-related diseases.

Impact of various solutions on the oral health status of critically ill patients.

Oral care is a crucial challenge of nursing care in orally intubated patients. Oropharyngeal colonization with microorganisms is probably the first step in the pathogenesis of most bacterial pulmonary infections. This study aimed to investigate the effect of different oral care solutions on the oral health status of critically ill patients. We conducted a quasi-experimental study involving a convenience sample of 60 adult orally intubated patients, distributed equally into three groups: 20 patients received 0.12% chlorhexidine gluconate (CHX) solution as an oral rinse; 20 patients received 0.1% hexetidine (HEX) solution as an oral rinse; and a control group of 20 patients received routine hospital oral care with 0.9% normal saline (NS) solution. Oropharyngeal and tracheal cultures were obtained from patients within 24-48 h of admission, before the administration of topical oral antimicrobial solutions and then repeated on day 4 and day 7 after the oral solutions. The study revealed that CHX has a more powerful effect than HEX and NS in improving the oral mucosa and decreasing colonization of both the oropharynx and trachea. On day 7, the improvements were statistically significant in the CHX group and the HEX group (P = 0.02 and P = 0.03, respectively), but not in the NS group. This research confirms the effect of CHX and HEX in lowering the risk of tracheal and oropharyngeal colonization, and recommends the use of a CHX solution as oral mouth care in critically ill patients.

Anatomical, pathological, and histological features of experimental respiratory infection of birds by biofilm-forming bacteria Staphylococcus aureus.

The pathogenesis of staphylococcal infections is mediated by virulence factors, such as enzymes, toxins, and biofilms, which increase the resistance of microorganisms to host immune system evasion. Testing and searching for standardized multi-level algorithms for the indication and differentiation of biofilms at the early stages of diagnosis will contribute to the development of preventive measures to control the critical points of technology and manage dangerous risk factors for the spread of infectious diseases. This research aimed to study the main stages of Staphylococcus aureus biofilm formation in in vitro experiments and to analyze the dynamics of respiratory syndrome development in chickens infected with these bacteria. Experimental reproduction of the infectious process was performed using laboratory models: 10-day-old White Leghorn chickens (n = 20). Before the experiments, the birds were divided into two groups according to the principle of analogs: Group I (control, n = 10): the birds were intranasally inoculated with 0.5 cm3 of 0.9% NaCl solution; Group II (experiment, n = 10): the birds were intranasally inoculated with a suspension of S. aureus bacteria, 0.5 cm3, concentration 1 billion/cm3. Colonization of individual areas of the substrate under study in vitro occurred gradually from the sedimentation and adhesion of single motile planktonic cells to the attachment stage of microcolony development. Staining preparations with gentian violet due to the "metachromosia" property of this dye are a quick and fairly simple way to differentiate cells and the intercellular matrix of biofilms. Fixation with vapors of glutaraldehyde and osmium tetroxide preserves the natural architecture of biofilms under optical and scanning electron microscopy. Pure cultures of S. aureus microorganisms were isolated from the blood, lungs, small intestine, liver, kidneys, and spleen after 5-10 days during experimental infection of chickens. Clinical signs of respiratory syndrome developed within 5-6 days after infection. Acute and subacute serous-fibrinous airsacculitis, characterized by edema and thickening of the membranes of the air sacs and the presence of turbid, watery, foamy contents in the cavity, was the most characteristic pathomorphological sign. The signs of acute congestive hyperemia and one-sided serous-fibrinous pneumonia developed with significant thickening of fibrinous deposits. In Garder's gland, there was an increase in the number of secretory sections, indicating hypersecretion of the glands. In the lymphoid follicles of Meckel's diverticulum, leukocytes, usually lymphocytes, and pseudoeosinophils were detected. Hydration and heteromorphism of the internal environment of biofilms determine the localization of differentiated cells in a three-dimensional matrix for protection against adverse factors. The most characteristic pathomorphological sign was the development of acute and subacute serous-fibrinous airsacculitis when reproducing the infectious process in susceptible models. There was a significant thickening of fibrinous deposits and signs of acute congestive hyperemia and one or two serous-fibrinous pneumonia developed.

Pathogenesis of viral infections during pregnancy.

SUMMARYViral infections during pregnancy are associated with significant adverse perinatal and fetal outcomes. Pregnancy is a unique immunologic and physiologic state, which can influence control of virus replication, severity of disease, and vertical transmission. The placenta is the organ of the maternal-fetal interface and provides defense against microbial infection while supporting the semi-allogeneic fetus via tolerogenic immune responses. Some viruses, such as cytomegalovirus, Zika virus, and rubella virus, can breach these defenses, directly infecting the fetus and having long-lasting consequences. Even without direct placental infection, other viruses, including respiratory viruses like influenza viruses and severe acute respiratory syndrome coronavirus 2, still cause placental damage and inflammation. Concentrations of progesterone and estrogens rise during pregnancy and contribute to immunological adaptations, placentation, and placental development and play a pivotal role in creating a tolerogenic environment at the maternal-fetal interface. Animal models, including mice, nonhuman primates, rabbits, and guinea pigs, are instrumental for mechanistic insights into the pathogenesis of viral infections during pregnancy and identification of targetable treatments to improve health outcomes of pregnant individuals and offspring.

Periprosthetic Joint Infection as a Socio-Economic Problem of Modern Orthopedics

Periprosthetic joint infection is the main social and economic problem of modern orthopedics with a recurrence rate of chronic forms of up to 23.2–31.5%. The aim of this review is to inform various specialties doctors about the features of pathogenesis, etiology and treatment of periprosthetic joint infection, which significantly differ it from of other surgical site infections. The severity of infectious complications is due to the suppression of the patient’s immune system and microbial biofilms. Surgical treatment of periprosthetic joint infection involves debridement with preservation or removal of the implants, resection arthroplasty and arthrodesis. Today, in the treatment of more than 80% of cases of chronic infection, a two-stage approach is used, which allows to restore joint function after an average of 1.0–1.5 years. An integral part of the treatment of patients is high-dose, long-term and combined antibiotic therapy, which allows you to effectively deal with the leading pathogens of periprosthetic infection Staphylococcus aureus and S. epidermidis, the share of which is 46.5–57.5%. In the conditions of growing resistance of bacteria to antibiotics, the interest of researchers in the possibilities of using bacteriophages in the complex therapy of infections of bones and joints has increased. The cost of treatment exceeds the cost of “aseptic” joint replacement by 2–24 times and is characterized by a high level of disability and mortality of patients. Taking into account the numerous factors affecting the course and effectiveness of complex treatment of patients with periprosthetic infection, a multidisciplinary approach is currently considered the main component of success. The medical and social significance and high financial costs of treating patients with periprosthetic infection indicate the need for further research and the active implementation of effective scientific developments in the practical healthcare system.

Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways

BackgroundThe rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers.MethodsThis investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein–protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data.ResultsOur proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium.ConclusionsThis study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

The Influence of Foxp3 Treg Cell Gene Polymorphism (rs3761548) on FoxP3 Gene Expression in Patients with Chronic Hepatitis B Virus Infection

: Immune responses are pivotal in hepatitis B virus (HBV) infection, where Regulatory T cells (Treg) can contribute to sustaining the infection by suppressing immune responses. Forkhead box P3 (FoxP3) is the central regulator of Treg cells. In this case-control study, we investigated the role of FoxP3 -3279 (rs3761548) C/A polymorphism in the context of HBV infection. The study encompassed 140 healthy individuals as the control group and 70 individuals with chronic hepatitis B virus (CHBV) as the case group. The rs3761548 polymorphism was analyzed using the restriction fragment length polymorphism-PCR (PCR-RFLP) method. Furthermore, we evaluated FoxP3 gene expression in both HBV-positive and control groups using Real-Time PCR. The results revealed that the frequency of the AA genotype in the case and control groups was 52.9% and 44.3%, respectively, yielding an odds ratio (OR) of 1.411 with a 95% confidence interval (CI) ranging from 0.793 to 2.509. However, this difference did not achieve statistical significance (P = 0.242). Notably, the AC genotype was significantly more prevalent in the control group compared to the case group (P = 0.000). Moreover, FoxP3 gene expression was significantly higher in CHBV infection cases compared to the control group (P = 0.000). These findings suggest that the observed polymorphism may play a role in the pathogenesis and persistence of HBV infection. Nevertheless, further research is warranted to comprehensively investigate this phenomenon.

Impact of normalized COVID-19 prevention and control measures on lower respiratory tract infection pathogenesis in hospitalized children.

This study aimed to investigate the epidemiological characteristics of common pathogens contributing to childhood lower respiratory tract infections (LRTIs) in Xiangtan City, Hunan Province before and during the coronavirus disease 2019 (COVID-19) pandemic. A total of 11,891 enrolled patients, aged 1 month to 14 years, diagnosed with LRTIs and admitted to Xiangtan Central Hospital from January 2018 to December 2021 were retrospectively reviewed in this study. Specifically, the epidemiological characteristics of these pathogens before and during the COVID-19 pandemic were analyzed. There was a significant decrease in the number of children hospitalized with LRTIs during the COVID-19 pandemic (2020-2021) compared to data from 2018 to 2019 (before the COVID-19 pandemic). Of these cases, 60.01% (7,136/11,891) were male and 39.99% (4,755/11,891) were female. 78.9% (9,381/11,891) cases occurred in children under 4 years of age. The average pathogen detection rate among 11,891 hospitalized LRTIs children was 62.19% (7,395/11,891), with the average pathogen detection rate of 60.33% (4,635/7,682) and 65.57% (2,670/4,209) before and during COVID-19 pandemic, respectively. The detection rates of adenovirus (ADV), bordetella pertussis (BP) and moraxella catarrhalis (M. catarrhalis) decreased dramatically, while the detection rates of influenza viruses (IFV), parainfluenza viruses (PIV), respiratory syncytial virus (RSV), haemophilus influenzae (H. influenzae), streptococcus pneumoniae (S. pneumoniae), and staphylococcus aureus (S. aureus) increased significantly during the COVID-19 pandemic. Overall, RSV, mycoplasma pneumoniae (MP), H. influenzae, and IFV were the major pathogens causing LRTIs in hospitalized children before and during the COVID-19 pandemic. Public health interventions for COVID-19 prevention are beneficial to reduce the incidence of LRTIs in children by limiting the prevalence of ADV, MP, BP, and M. catarrhalis, but which have limited restrictive effects on other common LRTIs-associated pathogens. Collectively, the data in this study comprehensively investigated the effects of COVID-19 pandemic on the epidemiological characteristics of respiratory pathogens, which will be beneficial for improving early preventive measures.

The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses.

APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3. Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3s in carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer.

A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified. To investigate the disease relevance of COVID-19 in liver cancer. Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed. Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the "cytoHubba" plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells. Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.