MicroRNA-155, a double-blade sword regulator of innate tuberculosis immunity.

Tuberculosis (TB) is a chronic, life-threatening disease caused by unusual facultative intracellular bacteria, Mycobacterium tuberculosis. This bacterium has unique resistance to many antimicrobial agents and has become a major global health concern due to emerging multidrug-resistant strains. Additionally, it has developed multiple schemes to exploit host immune signaling and establish long-term survival within host tissues. Thus, understanding the pathways that govern the crosstalk between the bacterium and the immune system could provide a new avenue for therapeutic interventions. MicroRNAs (miRs) are short, noncoding, and regulator RNA molecules that control the expression of cellular genes by targeting their mRNAs post-transcriptionally. MiR-155 is one of the most crucial miR in shaping the host immune defenses against M. tuberculosis. MiR-155 is remarkably downregulated in patients with clear clinical TB symptoms in comparison with latently infected patients and/or healthy individuals, thereby implicating its role in controlling M. tuberculosis infection. However, functional probing of miR-155 suggests dual effects in regulating the host's innate defenses in response to mycobacterial infection. This review provides comprehensive knowledge and future perspectives regarding complex signaling pathways that mediated miR-155 expression during M. tuberculosis infections. Moreover, miR-155-targeting signaling orchestrates inflammatory mediators' production, apoptosis, and autophagy.

The interleukin-10 family: Major regulators of the immune response against Plasmodium falciparum infections.

Malaria caused by the Plasmodium falciparum strain is more severe because of this protozoan's ability to disrupt the physiology of host cells during the blood stages of development by initiating the production of the interleukin-10 (IL-10) family of cytokines. P. falciparum feeds on hemoglobin and causes host cells to adhere to the walls of blood vessels by remodeling their composition. IL-10 is produced by CD4+ T cells that inhibits antigen-presenting cells' activity to prevent inflammation. This cytokine and its family members are crucial in promoting malarial infection by inhibiting the host's protective immune response, thus initiating Plasmodium parasitemia. IL-10 is also responsible for preventing severe pathology during Plasmodium infection and initiates several signaling pathways to alter the physiology of host cells during malarial infection. This review summarizes the critical aspects of P. falciparum infection, including its role in signaling pathways for cytokine exudation, its effect on microRNA, the human immune response in malaria, and the role played by the liver hormone hepcidin. Moreover, future aspects of vaccine development and therapeutic strategies to combat P. falciparum infections are also discussed in detail.

Bibliometric Analysis of Publications on the Omicron Variant from 2020 to 2022 in the Scopus Database Using R and VOSviewer.

Human respiratory infections caused by coronaviruses can range from mild to deadly. Although there are numerous studies on coronavirus disease 2019 (COVID-19), few have been published on its Omicron variant. In order to remedy this deficiency, this study undertook a bibliometric analysis of the publishing patterns of studies on the Omicron variant and identified hotspots. Automated transportation, environmental protection, improved healthcare, innovation in banking, and smart homes are just a few areas where machine learning has found use in tackling complicated problems. The sophisticated Scopus database was queried for papers with the term "Omicron" in the title published between January 2020 and June 2022. Microsoft Excel 365, VOSviewer, Bibliometrix, and Biblioshiny from R were used for a statistical analysis of the publications. Over the study period, 1917 relevant publications were found in the Scopus database. Viruses was the most popular in publications for Omicron variant research, with 150 papers published, while Cell was the most cited source. The bibliometric analysis determined the most productive nations, with USA leading the list with the highest number of publications (344) and the highest level of international collaboration on the Omicron variant. This study highlights scientific advances and scholarly collaboration trends and serves as a model for demonstrating global trends in Omicron variant research. It can aid policymakers and medical researchers to fully grasp the current status of research on the Omicron variant. It also provides normative data on the Omicron variant for visualization, study, and application.

Molecular Epidemiology of Extensively-Drug Resistant Acinetobacter baumannii Sequence Type 2 Co-Harboring bla NDM and bla OXA From Clinical Origin.

BACKGROUND: The therapeutic management of carbapenem-resistant Acinetobacter baumannii (CR-AB) represents a serious challenge to the public health sector because these pathogens are resistant to a wide range of antibiotics, resulting in limited treatment options. The present study was planned to investigate the clonal spread of CR-AB in a clinical setting. METHODOLOGY: A total of 174 A. baumannii clinical isolates were collected from a tertiary care hospitals in Lahore, Pakistan. The isolates were confirmed by VITEK 2 compact system and molecular identification of recA and bla OXA-51. Antimicrobial profile and the screening of carbapenem-resistant genes were carried out using VITEK 2 system and PCR, respectively. The molecular typing of the isolates was performed according to the Pasteur scheme. RESULTS: Of the 174 A. baumannii isolates collected, the majority were isolated from sputum samples (46.5%) and in the intensive care unit (ICU, 75%). Among these, 113/174 (64.9%) were identified as CR-AB, and 49.5% and 24.7% harbored bla OXA-23 and bla NDM-1, respectively. A total of 11 (9.7%) isolates co-harbored bla OXA-51, bla NDM-1, and bla OXA-23. Interestingly, 46.9% of the CR-AB belonged to sequence type 2 (ST2; CC1), whereas 15.9% belonged to ST1 (CC1). All of the CR-AB isolates showed extensive resistance to clinically relevant antibiotics, except colistin. CONCLUSION: The study concluded CR-AB ST2 clone harboring bla OXA-23 and bla NDM-1 are widely distributed in Pakistan's clinical settings, which could result in increased mortality. Strict compliance with the National Action Plan on Antimicrobial Resistance is necessary to reduce the impacts of these strains.

Molecular Epidemiology of Extensively Drug-Resistant mcr Encoded Colistin-Resistant Bacterial Strains Co-Expressing Multifarious ß-Lactamases.

Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious ß-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory concentration (MIC) breakpoint ≥4 µg/mL. Resistant isolates were examined for mcr variants, extended-spectrum ß-lactamase, AmpC, and carbapenemase genes using polymerase chain reaction (PCR). The MIC breakpoints for mcr-positive strains were determined using broth microdilution and E-test strips. Overall, 19/718 (2.6%) gram-negative rods (GNRs) harboring mcr were identified, particularly in pus (p = 0.01) and tracheal secretions (p = 0.03). Molecular epidemiology data confirmed 18/19 (95%) mcr-1 and 1/19 (5%) mcr-2 genes. Integron detection revealed 15/17 (88%) Int-1 and 2/17 (12%) Int-2. Common co-expressing drug-resistant ß-lactamase genes included 8/16 (50%) blaCTM-1, 3/16 (19%) blaCTM-15, 3/3 (100%) blaCMY-2, 2/8 (25%) blaNDM-1, and 2/8 (25%) blaNDM-5. The MIC50 and MIC90 values (µg/mL) were as follows: Escherichia coli, 12 and 24; Klebsiella pneumoniae, 12 and 32; Acinetobacter baumannii, 8 and 12; and Pseudomonas aeruginosa, 32 and 64, respectively. Treatment of XDR strains has become challenging owing to the co-expression of mcr-1, mcr-2, multifarious ß-lactamase genes, and integrons.

Heavy Metal Tolerance Trend in Extended-Spectrum ß-Lactamase Encoding Strains Recovered from Food Samples.

This study evaluates bacteriological profiles in ready-to-eat (RTE) foods and assesses antibiotic resistance, extended-spectrum ß-lactamase (ESBL) production by gram-negative bacteria, and heavy metal tolerance. In total, 436 retail food samples were collected and cultured. The isolates were screened for ESBL production and molecular detection of ESBL-encoding genes. Furthermore, all isolates were evaluated for heavy metal tolerance. From 352 culture-positive samples, 406 g-negative bacteria were identified. Raw food samples were more often contaminated than refined food (84.71% vs. 76.32%). The predominant isolates were Klebsiella pneumoniae (n = 76), Enterobacter cloacae (n = 58), and Escherichia coli (n = 56). Overall, the percentage of ESBL producers was higher in raw food samples, although higher occurrences of ESBL-producing E. coli (p = 0.01) and Pseudomonas aeruginosa (p = 0.02) were observed in processed food samples. However, the prevalence of ESBL-producing Citrobacter freundii in raw food samples was high (p = 0.03). Among the isolates, 55% were blaCTX-M, 26% were blaSHV, and 19% were blaTEM. Notably, heavy metal resistance was highly prevalent in ESBL producers. These findings demonstrate that retail food samples are exposed to contaminants including antibiotics and heavy metals, endangering consumers.

Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense.

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host's signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.

Intelligent Mechanisms of Macrophage Apoptosis Subversion by Mycobacterium.

Macrophages are one of the first innate defense barriers and play an indispensable role in communication between innate and adaptive immune responses, leading to restricted Mycobacterium tuberculosis (Mtb) infection. The macrophages can undergo programmed cell death (apoptosis), which is a crucial step to limit the intracellular growth of bacilli by liberating them into extracellular milieu in the form of apoptotic bodies. These bodies can be taken up by the macrophages for the further degradation of bacilli or by the dendritic cells, thereby leading to the activation of T lymphocytes. However, Mtb has the ability to interplay with complex signaling networks to subvert macrophage apoptosis. Here, we describe the intelligent strategies of Mtb inhibition of macrophages apoptosis. This review provides a platform for the future study of unrevealed Mtb anti-apoptotic mechanisms and the design of therapeutic interventions.

Human cytomegalovirus-encoded MicroRNAs: A master regulator of latent infection.

Human cytomegalovirus (HCMV) can modulate the host cell microenvironment to cause latent infection and is therefore considered a major health concern in immunocompromised patients. HCMV-encoded microRNAs (miRs) have emerged as a key player in regulating the expression of the host cell and viral genes to induce latent infection. HCMV-encoded miRs can inhibit antiviral immune responses, such as proinflammatory mediators production, antigenic presentation, and apoptosis. In addition, HCMV miRs can reduce viral DNA replication. In this review, we describe the mechanisms underlying HCMV-encoded miR-mediated regulation of latent infection that may be exploited for future designing novel miRs-directed therapies.