Infection Disease Progression Research Articles

Ferroptosis: A mixed blessing for infectious diseases.

To date, it has been confirmed that the occurrence and development of infectious diseases are tightly associated with regulatory cell death processes, such as apoptosis, autophagy, and necroptosis. Ferroptosis, as a newly discovered form of regulatory cell death characterized by iron-dependent lipid peroxidation, is not only closely associated with tumor progression, but is also found to be tightly related to the regulation of infectious diseases, such as Tuberculosis, Cryptococcal meningitis, Malaria and COVID-2019. The emerging critical roles of ferroptosis that has been found in infectious disease highlight ferroptosis as a potential therapeutic target in this field, which is therefore widely expected to be developed into new therapy strategy against infectious diseases. Here, we summarized the underlying mechanisms of ferroptosis and highlighted the intersections between host immunity and ferroptosis. Moreover, we illuminated the roles of ferroptosis in the occurrence and progression of different infectious diseases, which might provide some unique inspiration and thought-provoking perspectives for the future research of these infectious diseases, especially for the development of ferroptosis-based therapy strategy against infectious diseases.

Two decades of tuberculosis surveillance reveal disease spread, high levels of exposure and mortality and marked variation in disease progression in wild meerkats.

Infections with tuberculosis (TB)-causing agents of the Mycobacterium tuberculosis complex threaten human, livestock and wildlife health globally due to the high capacity to cross trans-species boundaries. Tuberculosis is a cryptic disease characterized by prolonged, sometimes lifelong subclinical infections, complicating disease monitoring. Consequently, our understanding of infection risk, disease progression, and mortality across species affected by TB remains limited. The TB agent Mycobacterium suricattae was first recorded in the late 1990s in a wild population of meerkats inhabiting the Kalahari in South Africa and has since spread considerably, becoming a common cause of meerkat mortality. This offers an opportunity to document the epidemiology of naturally spreading TB in a wild population. Here, we synthesize more than 25 years' worth of TB reporting and social interaction data across 3420 individuals to track disease spread, and quantify rates of TB social exposure, progression, and mortality. We found that most meerkats had been exposed to the pathogen within eight years of first detection in the study area, with exposure reaching up to 95% of the population. Approximately one quarter of exposed individuals progressed to clinical TB stages, followed by physical deterioration and death within a few months. Since emergence, 11.6% of deaths were attributed to TB, although the true toll of TB-related mortality is likely higher. Lastly, we observed marked variation in disease progression among individuals, suggesting inter-individual differences in both TB susceptibility and resistance. Our results highlight that TB prevalence and mortality could be higher than previously reported, particularly in species or populations with complex social group dynamics. Long-term studies, such as the present one, allow us to assess temporal variation in disease prevalence and progression and quantify exposure, which is rarely measured in wildlife. Long-term studies are highly valuable tools to explore disease emergence and ecology and study host-pathogen co-evolutionary dynamics in general, and its impact on social mammals.

Cellular heterogeneity in disease severity and clinical outcome: Granular understanding of immune response is key.

During an infectious disease progression, it is crucial to understand the cellular heterogeneity underlying the differential immune response landscape that will augment the precise information of the disease severity modulators, leading to differential clinical outcome. Patients with COVID-19 display a complex yet regulated immune profile with a heterogeneous array of clinical manifestation that delineates disease severity sub-phenotypes and worst clinical outcomes. Therefore, it is necessary to elucidate/understand/enumerate the role of cellular heterogeneity during COVID-19 disease to understand the underlying immunological mechanisms regulating the disease severity. This article aims to comprehend the current findings regarding dysregulation and impairment of immune response in COVID-19 disease severity sub-phenotypes and relate them to a wide array of heterogeneous populations of immune cells. On the basis of the findings, it suggests a possible functional correlation between cellular heterogeneity and the COVID-19 disease severity. It highlights the plausible modulators of age, gender, comorbidities, and hosts’ genetics that may be considered relevant in regulating the host response and subsequently the COVID-19 disease severity. Finally, it aims to highlight challenges in COVID-19 disease that can be achieved by the application of single-cell genomics, which may aid in delineating the heterogeneity with more granular understanding. This will augment our future pandemic preparedness with possibility to identify the subset of patients with increased diseased severity.

Multiparametric approach to assess the disease severity and progression of cutaneous leishmaniasis infection

The pathophysiology of Cutaneous Leishmaniasis (CL), an infection caused by Leishmania tropica (L. tropica) and Leishmania major (L. major) is primarily determined by inflammation-mediated immune cells. The immune response mainly depends on cells and molecules related to T-cells that influence susceptibility and disease development. Understanding the immunological mechanisms that cause tissue injury or lesion healing is critical for developing appropriate treatment strategies. In the present study, T-cells profile and cell-free mitochondrial DNA (CF mt-DNA) were investigated in CL patients infected with L. tropica (n = 34) and L. major (n = 2) and compared with non-infected healthy controls (n = 20). There was a significant (p<0.0001) difference between CD4+ T-cells among L. tropica and L. major CL-infected groups as compared to control while no significant difference (p = 0.8597) was found in the percentages of CD8+ T-cells. When L. tropica and L. major CL-infected individuals were compared to controls, the levels of IL-4 and expression of CF mt-DNA were significantly higher (p<0.0001). Higher levels of CF mt-DNA were detected in CL patients, irrespective of the infective Leishmania species. We proposed that the levels of CF mt-DNA and IL-4 in CL-infected individuals can be used to determine the disease progression. A better understanding of these biomarkers and evaluation of the immune responses in CL patients might benefit the development of vaccines and immunotherapies.

Win ratio approach for analyzing composite time-to-event endpoint with opposite treatment effects in its components.

There is an increasing interest in the use of win ratio with composite time-to-event due to its flexibility in combining component endpoints. Exploring this flexibility further, one interesting question is in assessing the impact when there is a difference in treatment effect in the component endpoints. For example, the active treatment may prolong the time to occurrence of the negative event such as death or ventilation; meanwhile, the treatment effect may also shorten the time to achieving positive events, such as recovery or improvement. Notably, this portrays a situation where the treatment effect on time to recovery is in a different direction of benefit compared to the time to ventilation or death. Under such circumstances, if a single endpoint is used, the benefit gained for other individual outcomes is not counted and is diminished. As consequence, the study may need a larger sample size to detect a significant effect of treatment. Such a scenario can be handled by win ratio in a novel way by ranking component events, which is different from the usual composite endpoint approach such as time-to-first event. To evaluate how the different directions of treatment effect on component endpoints will impact the win ratio analysis, we use a Clayton copula-based bivariate survival simulation to investigate the correlation of component time-to-event. Through simulation, we found that compared to the marginal model using single endpoints, the win ratio analysis on composite endpoint performs better, especially when the correlation between two events is weak. Then, we applied the methodology to an infectious disease progression simulated study motivated by COVID-19. The application demonstrates that the win ratio approach offers advantages in empirical power compared to the traditional Cox proportional hazard approach when there is a difference in treatment effect in the marginal events.

Recent Development of Macrocyclic Compounds as Potential Tool for Cancer Therapy and Diagnosis: A Mini-Review

Macrocyclic compounds can be easily sustained into varied functionality, which has recently famed them as an individual supramolecular entity. Owing to their tenable non-covalent interactions or dynamic covalent bonding, these macrocyclic formulations have contemporaneously inhibited and controlled the progression of infectious diseases and cancers. Macrocyclic supramolecular assemblies have been fabricated for staging the medicinal accuracy of different therapies as well as diagnostic pathways. This mini-review, therefore, focuses on the design of a hierarchical assembly process at the molecular level of chemical composition and presents interesting illustrations of supramolecular assembled structural motifs as new cancer diagnostic and therapeutic options.

Surge of Bell's Palsy in the era of COVID-19: Systematic review.

With the progression of coronavirus infectious disease 2019 (COVID-19), various neurological manifestations have been noticed in infected patients, and Bell's Palsy (BP) is one of the peripheral neuropathies among those. BP has been associated with various other viral agents. Its evidence in patients with COVID-19 signifies the possibility of association between BP and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This research was undertaken to evaluate the number of published cases of BP as the only major neurological manifestation in patients with COVID-19 from March 2020 to December 2021 and to investigate the association of SARS-CoV-2 and BP. A systematic review of the published English literature was performed using an electronic search in the PubMed/Medline, Scopus, Research Gate, Research Square, and Google Scholar databases, using keywords such as "COVID-19" OR/AND "SARS-CoV-2" OR/AND "Bell's palsy" OR/AND "facial nerve palsy" OR/AND "neurological" OR/AND "manifestation". The search strategy revealed 32 relevant publications with a total of 46 patients. BP was the initial manifestation in 37% of cases, and in 63% of cases it developed after COVID-19symptoms; 71.7% of cases showed complete recovery, and 21.7% showed only partial relief from BP. Although the number of documented cases in this research is low, evidence of BP as the only major neurological manifestation in patients with COVID-19signifies an important clinical finding and the possibility of another viral etiology of BP. More evidence is needed to establish the exact correlation between these two entities.

Alinity m, a Random-Access System, for Hepatitis B Virus DNA Quantification in Plasma and Whole Blood Collected on Dried Blood Spots.

ABSTRACTThe International Liver Association recommends the use of accurate and sensitive molecular methods for determination of hepatitis B virus (HBV) DNA levels in plasma or serum of chronic HBsAg carriers. The level of HBV replication represents the strongest predictive biomarker associated with disease progression and long-term outcome of chronic HBV infection. The purpose of this study was to evaluate the ability to the new Alinity m System to detect and quantify HBV DNA in plasma and whole blood collected on dried blood spots (DBS). Paired plasma and DBS samples from patients chronically infected with various HBV genotypes were tested in parallel for HBV DNA detection and quantification. There is a linear relationship between HBV DNA levels measured in plasma samples using the Alinity m HBV assay and the Xpert HBV viral load assay, used for comparison. A slight deviation (0.03 ± 0.31 log IU/mL) was observed within the quantitative range. In DBS, HBV DNA levels closely correlated with levels measured in plasma. All patients had detectable and quantifiable HBV DNA by DBS testing, except for one patient with a plasma HBV DNA level above 2,000 IU/mL. In conclusion, the newly developed real-time PCR-based assay Alinity m HBV assay can correctly detect HBV DNA in DBS, especially for patients with blood HBV DNA levels above 2,000 IU/mL, and also accurately quantify HBV DNA in plasma samples.IMPORTANCE Hepatitis B virus is one of the most prevalent blood-borne viruses affecting the liver and causing acute and chronic hepatitis. Only a small proportion of people with HBV infection are diagnosed. HBV DNA measurement is critical in clinical practice for the diagnosis and treatment decisions of patients requiring antiviral therapy. Dried blood spot (DBS) collection provides a simple, practical, and acceptable alternative to venous blood collection, especially in community settings. We have demonstrated high sensitivity and specificity for HBV DNA detection in DBS compared to plasma samples, especially when using clinically relevant cutoffs of 2,000 and 20,000 IU/mL. Results support the use of DBS in community-based settings.

Complete Genome Characterization of Reticuloendotheliosis Virus Detected in Chickens with Multiple Viral Coinfections.

Reticuloendotheliosis virus (REV) is a retroviral pathogen capable of infecting several avian hosts and is associated with immunosuppression, anemia, proventriculitis, neoplasia, and runting–stunting syndrome. Its genome contains the three major genes, gag, pol, and env, and two flanking long terminal repeat (LTR) regions. Complete genome sequences of REV are limited in terms of geographical origin. The aim of this study was to characterize the complete genome of REV detected in Brazilian chickens with multiple viral coinfections and analyze the polymorphisms in the deduced amino acids sequences corresponding to its encoded proteins. We tested the presence and completeness of REV as well as other viral pathogens in samples from Brazilian poultry farms by qPCR. The complete genomes of two REV strains were sequenced by overlapping fragments through the dideoxy method. Phylogenetic analysis, pairwise identity matrix, polymorphism identification and protein modeling were performed along the entire genome. We detected REV in 65% (26/40) of the tested samples. Concomitant viral infections were detected in 82.5% (33/40) of the samples and in 90% (9/10) of the farms. Multiple infections included up to seven viruses. Phylogenetic analysis classified both Brazilian strains into REV subtype 3, and the pairwise comparison indicated that strains from the USA and fowlpox virus (FWPV)-related strains were the most identical. The subdomain p18 in gag, the reverse transcriptase/ribonuclease H in pol, and the surface (SU) in the env protein were the most polymorphic in genomic comparisons. The relevant motifs for each protein were highly conserved, with fewer polymorphisms in the fusion peptide, immunosuppression domain, and disulfide bonds on the surface (SU) and transmembrane (TM) of env. This is the first study to include complete genomes of REV in Brazil and South America detected in farms with multiple viral coinfections. Our findings suggest an involvement of REV as an immunosuppressor and active agent in the emergence and progression of multiple infectious diseases. We also found a possible etiological relationship between Brazilian strains and the USA and FWPV recombinant strains. This information highlights the need for epidemiological vigilance regarding REV in association with another pathogens.

Discriminant models for the prediction of postponed viral shedding time and disease progression in COVID-19

BackgroundCOVID-19 infection can cause life-threatening respiratory disease. This study aimed to fully characterize the clinical features associated with postponed viral shedding time and disease progression, then develop and validate two prognostic discriminant models.MethodsThis study included 125 hospitalized patients with COVID-19, for whom 44 parameters were recorded, including age, gender, underlying comorbidities, epidemiological features, laboratory indexes, imaging characteristics and therapeutic regimen, et al. Fisher's exact test and Mann–Whitney test were used for feature selection. All models were developed with fourfold cross-validation, and the final performances of each model were compared by the Area Under Receiving Operating Curve (AUROC). After optimizing the parameters via L2 regularization, prognostic discriminant models were built to predict postponed viral shedding time and disease progression of COVID-19 infection. The test set was then used to detect the predictive values via assessing models’ sensitivity and specificity.ResultsSixty-nine patients had a postponed viral shedding time (> 14 days), and 28 of 125 patients progressed into severe cases. Six and eleven demographic, clinical features and therapeutic regimen were significantly associated with postponed viral shedding time and disease progressing, respectively (p < 0.05). The optimal discriminant models are: y1 (postponed viral shedding time) = − 0.244 + 0.2829x1 (the interval from the onset of symptoms to antiviral treatment) + 0.2306x4 (age) + 0.234x28 (Urea) − 0.2847x34 (Dual-antiviral therapy) + 0.3084x38 (Treatment with antibiotics) + 0.3025x21 (Treatment with Methylprednisolone); y2 (disease progression) = − 0.348–0.099x2 (interval from Jan 1st,2020 to individualized onset of symptoms) + 0.0945x4 (age) + 0.1176x5 (imaging characteristics) + 0.0398x8 (short-term exposure to Wuhan) − 0.1646x19 (lymphocyte counts) + 0.0914x20 (Neutrophil counts) + 0.1254x21 (Neutrphil/lymphocyte ratio) + 0.1397x22 (C-Reactive Protein) + 0.0814x23 (Procalcitonin) + 0.1294x24 (Lactic dehydrogenase) + 0.1099x29 (Creatine kinase).The output ≥ 0 predicted postponed viral shedding time or disease progressing to severe/critical state. These two models yielded the maximum AUROC and faired best in terms of prognostic performance (sensitivity of78.6%, 75%, and specificity of 66.7%, 88.9% for prediction of postponed viral shedding time and disease severity, respectively).ConclusionThe two discriminant models could effectively predict the postponed viral shedding time and disease severity and could be used as early-warning tools for COVID-19.

Mast-Cell Response to Leishmania mexicana and Sand-Fly Salivary Proteins Is Modulated by Orchiectomy.

Mast cells (MCs) play a crucial role during Leishmania infections, which is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response and alter susceptibility to infections. Thus, to assess the impact of male sex hormones on the mast-cell (MC) response to Leishmania infections, we orchiectomized male mice, infected them with the parasite in the presence of sand fly salivary proteins, and analyzed the inflammatory response of MCs. Our results showed that the MC response to the parasite and vector salivary proteins differed between orchiectomized and sham-operated mice. In orchiectomized mice, MC showed a retarded activation pattern, associated with slower degranulation and weaker TNF-α, histamine, and tryptase staining in response to the infection with Leishmania mexicana combined with vector-salivary proteins, as compared to sham mice. Furthermore, neutrophil infiltration was slower in orchiectomized mice, and numbers of infected macrophages and lesion sizes were smaller. Our results show that, during Leishmania infection, male sex hormones modulate the mast-cell response against the parasite and salivary proteins of the sand fly vector, inducing an intense inflammatory response. Their absence in orchiectomized mice retards the inflammatory response, enabling better control of the infection and slower disease progression.

A one year follow of patients with multiple sclerosis during COVID-19 pandemic: A cross-sectional study in Qom province, Iran

BackgroundIn the current COVID-19 pandemic, Multiple Sclerosis (MS) patients represent a population of particular interest as they might be at higher risk of COVID-19 infection and it's complications. The present study aimed to investigate a one year follow up of patients with MS during the COVID-19 pandemic, in Qom province, Iran. MethodsThis study was performed at the MS Clinic of Beheshti Hospital from June 1, 2020 to November 1, 2021. 202 patients with a diagnosis of MS and negative self-reported history of COVID-19 at the beginning of the pandemic, were enrolled. First, the demographic characteristics of patients were collected. Second, the patients underwent serological testing for anti-SARS-CoV-2 IgG antibodies. Then, a year later, they were revalauted and asked about the occurrence of clinical relapse leading to hospitalization, disease progression, DMT profile, COVID-19 vaccination, and history of COVID-19 infection. We considered six weeks after COVID-19 regarding relapse occurrence. Eventually, statistical analysis was carried out by using SPSS 26.0 ResultsOf 202 patients, 26 patients (12.87%) had initially a positive index antibody result. During the follow-up periods, 25 patients (12.37%) were infected with COVID-19 which was mainly mild (74.8%), and significantly lower than general population. 118 patients (58.41%) were vaccinated for COVID-19 which reduced the risk of COVID-19 development (P<001). Except a case of myelitis associated with vaccination, no serious adverse event was reported. Additionally, only one patient developed MS relapse following COVID-19 infection. Except clinical relapse (P = 0.001), other demographic and MS characteristics, and DMT type were not associated with COVID-19. In terms of MS course, 12 patients (5.94%) discontinued their DMTs regardless of the DMT adverse events or treatment failure. 41 patients (20.3%) experienced a clinical relapse, of whom 12 were escalated to a second line DMT. Further, 27 patients (13.4%) noted a history of worsening disability which mainly occurred after COIVD-19 infection. ConclusionThe present study showed a significant lower incidence of COVID-19 infection in MS patients. Except for clinical relapse, other demographic and MS characteristics, and DMT type were not associated with COVID-19 infection. In addition, COVID-19 vaccination reduced the risk of COVID-19 development, and the prognosis was favorable in the majority of MS patients.

High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium.

ABSTRACTInteractions between individual pathogenic microbes and host tissues involve fast and dynamic processes that ultimately impact the outcome of infection. Using live-cell microscopy, these dynamics can be visualized to study, e.g., microbe motility, binding and invasion of host cells, and intrahost-cell survival. Such methodology typically employs confocal imaging of fluorescent tags in tumor-derived cell line infections on glass. This allows high-definition imaging but poorly reflects the host tissue’s physiological architecture and may result in artifacts. We developed a method for live-cell imaging of microbial infection dynamics on human adult stem cell-derived intestinal epithelial cell (IEC) layers. These IEC layers are grown in apical imaging chambers, optimized for physiological cell arrangement and fast, but gentle, differential interference contrast (DIC) imaging. This allows subsecond visualization of both microbial and epithelial surface ultrastructure at high resolution without using fluorescent reporters. We employed this technology to probe the behavior of two model pathogens, Salmonella enterica serovar Typhimurium and Giardia intestinalis, at the intestinal epithelial surface. Our results reveal pathogen-specific swimming patterns on the epithelium and show that Salmonella lingers on the IEC surface for prolonged periods before host cell invasion, while Giardia uses circular swimming with intermittent attachments to scout for stable adhesion sites. The method even permits tracking of individual Giardia flagella, demonstrating that active flagellar beating and attachment to the IEC surface are not mutually exclusive. This work describes a generalizable and relatively inexpensive approach to resolving dynamic pathogen-IEC layer interactions, applicable even to genetically nontractable microorganisms.

Multifractal analysis of chest CT images of patients with the 2019 novel coronavirus disease (COVID-19)

The present study was done to evaluate chest computed tomography (CT) images of patients with 2019 novel coronavirus disease (COVID-19) by multifractal technique as a new method to find a way for comparing lung infection quantitatively and identifying progression pattern of the disease. The multifractal spectra extracted from analysis of CT images showed that these spectra were correlated with lung infection amount and disease progression so that, multifractal parameters (αmin, αmax, ∆α, f(αmin), f(αmax), ∆f(α), α(q = 0), and f(α) max) were strongly dependent on amount of lung infection. The results demonstrated that multifractality of chest CT images was increased with the increase in lung infection in patients. The interesting and promising result was that capacity dimension (D0) as a new diagnostic parameter varied linearly with progression and reduction of lung infection. A critical value was found for D0, according to which patients with D0 lower than 1.4 can be healed by treatment. Therefore, herein, a way was found for quantitative assessment of lung infection of patients with COVID-19 by analyzing chest CT images using the multifractal method. This method can be very effective for physicians in diagnosis and treatment of pneumonia caused by COVID-19 and timely identification of therapeutic effects.

Label-Free Classification of Bacterial Extracellular Vesicles by Combining Nanoplasmonic Sensors With Machine Learning

Bacterial extracellular vesicles (EVs) are nano- scale lipid-enclosed packages that are released by bacteria cells and shuttle various biomolecules between bacteria or host cells. They are implicated in playing several important roles, from infectious disease progression to maintaining proper gut health, however the tools available to characterise and classify them are limited and impractical for many applications. Surface-enhanced Raman Spectroscopy (SERS) provides a promising means of rapidly fingerprinting bacterial EVs in a label-free manner by taking advantage of plasmonic resonances that occur on nanopatterned surfaces, effectively amplifying the inelastic scattering of incident light. In this study, we demonstrate that by applying machine learning algorithms to bacterial EV SERS spectra, EVs from cultures of the same bacterial species ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Escherichia coli</i> ) can be classified by strain, culture conditions, and purification method. While these EVs are highly purified and homogeneous compared to complex samples, the ability to classify them from a single species demonstrates the incredible power of SERS when combined with machine learning, and the importance of considering these parameters in future applications. We anticipate that these findings will play a crucial role in developing the laboratory and clinical utility of bacterial EVs, such as the label-free, noninvasive, and rapid diagnosis of infections without the need to culture samples from blood, urine, or other fluids.

Collective behavior of magnetic microrobots through immuno-sandwich assay: On-the-fly COVID-19 sensing

Mobile self-propelled micro/nanorobots are mobile binding surface that improved the sensitivity of many biosensing system by “on-the-fly” identification and isolation of different biotargets. Proteins are powerful tools to predict infectious disease progression such as COVID-19. The main methodology used to COVID-19 detection is based on ELISA test by antibodies detection assays targeting SARS-CoV-2 virus spike protein and nucleocapside protein that represent an indirect SARS-CoV-2 detection with low sentitivy and specificity. Moreover ELISA test are limited to used external shaker to obtain homogenously immobilization of antibodies and protein on sensing platform. Here, we present magnetic microrobots that collective self-assembly through immuno-sandwich assay and they can be used as mobile platform to detect on-the-fly SARS-CoV-2 virus particle by its spike protein. The collective self-assembly of magnetic microrobots through immuno-sandwich assay enhanced its analytical performance in terms of sensitivity decreasing the detection limit of SARS-CoV-2 virus by one order of magnitude with respect to the devices previously reported. This proof-of-concept of microrobotics offer new ways to the detection of viruses and proteins of medical interest in general.

The role of gut microbiota in infectious diseases.

The intestine, the largest immune organ in the human body, harbors approximately 1013 microorganisms, including bacteria, fungi, viruses, and other unknown microbes. The intestine is a most important crosstalk anatomic structure between the first (the host) and second (the microorganisms) genomes. The imbalance of the intestinal microecology, especially dysbiosis of the composition, structure, and function of gut microbiota, is linked to human diseases. In this review, we investigated the roles and underlying mechanisms of gut microecology in the development, progression, and prognosis of infectious diseases. Furthermore, we discussed potential new strategies of prevention and treatment for infectious diseases based on manipulating the composition, structure, and function of intestinal microorganisms in the future. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.

Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression.

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n=186), liver cirrhosis (LC, n=142) and hepatocellular carcinoma (HCC, n=223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR=1.6; 95%CI=1.1-2.3; p=0.0087) and disease progression (LC vs. CHB: OR=1.8; 95%CI=1.1-2.9; p=0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p<0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C>B>A, p<0.0001) and BCLC classification (BCLC D>C>B>A, p=0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.

The involvement of microRNAs in HCV and HIV infection.

Approximately 2.3 million people are suffering from human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection worldwide. Faster disease progression and increased mortality rates during the HIV/HCV co-infection have become global health concerns. Effective therapeutics against co-infection and complete infection eradication has become a mandatory requirement. The study of small non-coding RNAs in cellular processes and viral infection has so far been beneficial in various terms. Currently, microRNAs are an influential candidate for disease diagnosis and treatment. Dysregulation in miRNA expression can lead to unfavorable outcomes; hence, this exact inevitable nature has made various studies a focal point. A considerable improvement in comprehending HIV and HCV mono-infection pathogenesis is seen using miRNAs. The prominent reason behind HIV/HCV co-infection is seen to be their standard route of transmission, while some pieces of evidence also suspect viral interplay between having a role in increased viral infection. This review highlights the involvement of microRNAs in HIV/HCV co-infection, along with their contribution in HIV mono- and HCV mono-infection. We also discuss miRNAs that carry the potentiality of becoming a biomarker for viral infection and early disease progression.

Correlation between plasma levels of sPD-1 and sPD-L1 with hepatic inflammation in chronic HBV infected patients

Objective: The immunosuppressive PD-1/PD-L1 (programmed cell death-1/ programmed cell death ligand-1) signaling pathway is considered to play an important role in the pathogenesis of HBV infection. We conducted a prospective cohort study to assess the relationship between circulating sPD-1 and sPD-L1 (soluble forms) levels in HBV infection and live disease outcome and progression. Subject and method: Plasma sPD-1 and sPD-L1 levels were quantified using commercial ELISA kits in a prospective cohort including asymptomatic carrier (ASY, n = 30), chronic hepatitis (CHB, n = 79), hepatocellular carcinoma (HCC, n = 47) and 73 healthy individuals as control group (HC). Result: The plasma sPD-1 and sPD-L1 levels were significantly higher in HBV infected patients or in each patient groups (ASY, CHB, HCC) compared to the controls (p&lt;0.0001). Among HBV-infected patients, plasma sPD-1 and sPD-L1 levels were higher in the CHB followed by the HCC and ASY group. The plasma levels of sPD-1 and sPD-L1 were positively correlated with hepatic inflammation markers such as AST, ALT and GGT in HBV- infected patients. Conclusion: We could show that HBV infection can induce the expression of PD-1 and PD-L1 and significantly increased levels of plasma sPD-1 and sPD-L1 are correlated with the hepatic inflammation in chronic HBV-infected patients.