Herpesvirus Infection Research Articles

Infection risk with JAK inhibitors in dermatoses: a meta-analysis.

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo-controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta-analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta-analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61-1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32-1.31, P = 0.23). The incidence of varicella-zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08-2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93-2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13-2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella-zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short-term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections.

Epidemiological characteristics of three herpesviruses infections in children in Nanjing, China, from 2018 to 2023.

To evaluate the epidemiology characteristics of Herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection in children from January 2018 to December 2023, in Nanjing, China. We conducted a retrospective analysis of 21,210, 49,494 and 32,457 outpatients and inpatients aged 1 day to 17 years who were subjected to the three herpesviruses (HSV-2, EBV, and CMV) nucleic acid testing from January 2018 to December 2023, respectively. Demographic information, laboratory findings, etc. were collected and analyzed. HSV-2, EBV and CMV nucleic acid testing were performed by real-time PCR. The total rate of detection of the three herpesviruses for all specimens was 0.32% (67/21,210), 14.99% (7419/49,494), and 8.88% (2881/32,457), respectively. A declining trend in the incidence of viral infections over the years was observed for the three herpesviruses (all P<0.05). The detection rate for HSV-2, EBV, and CMV was highest among patients aged 1-3 years, 3-7 years, and 28 days to 1 year, respectively (all P<0.05). The presence of HSV-2 and CMV infection did not exhibit a discernible seasonal pattern, whereas EBV typically demonstrated an elevation during the summer and autumn. EBV and CMV were both prevalent among children in China, except for HSV-2. The annual prevalence of the three herpesviruses show decreasing trend from 2018 to 2023, and no difference in gender (except for EBV). EBV infections usually occur in the summer and autumn, whereas HSV-2 and CMV do not exhibit significant seasonality. The positivity rate of HSV-2 is highest in 1-3 years, EBV is highest in 3-7 years, and that of CMV is highest in 28 days to 1 year. Positive detection rates are higher in outpatients than in inpatients.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Indirect Immunofluorescence Test for Detecting HSV-1, 2 in Patients with Esophageal Cancer: A Pilot Cross-Sectional Survey in Kazakhstan.

To evaluate the detectability of herpes simplex virus type 1 and 2 (HSV-1, 2) antigens in the esophageal mucosa in esophageal cancer. A cross-sectional pilot study with a control group was conducted from December 2022 to May 2023. The patients were divided into two groups: the main group with verified esophageal cancer and the control group without esophageal cancer based on the histological report. Diagnosis using fibroesophagogastroscopy (FEGS), histological analysis, and indirect immunofluorescence reaction (iIFR) was accomplished according to indications at the outpatient center of the endoscopic department of the Multidisciplinary Medical Center, Astana. Descriptive statistics and nonparametric methods were used to analyze the data. A total of 30 patients were recruited in the study, with 15 patients in the main group and 15 patients in the control group. HSV-1 and HSV-2 antigens were detected in the 13 cases (86.7%) during the study of biomaterial from patients with confirmed esophageal cancer in the main group and only in one case (6.8%) in the control group (95% CI 7.35 - 1126.9%, p=0.001). The presence of lymphocytic infiltration was detected in 13 cases (86.7%) in the main group and in 5 cases (33.3%) in the control group (95% CI 2.07 - 81.48%, p = 0.008). The process of keratinization was identified in HSV-1,2 antigens positive cases in the main group in 5 cases (35.7%) G1, in 5 cases (35.7%) G2, and in 3 cases (21.4 %) G3 (95% CI 1.66 - 656.23%, p=0.002). Overall, the local activity of herpesvirus infection to a certain extent influences the malignant potential of tumor cells and the resistance of surrounding healthy tissues. A large-scale study is still needed to confirm these results. The present pilot study provided an overview of a possible method for detecting HSV-1,2 activity in malignant tissue from esophageal cancer.

Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.

To investigate the association between Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection and both all-cause and cardiovascular mortality in a representative cohort of US adults, data from the National Health and Nutrition Examination Survey III (NHANES III; 1988‒1994) were analyzed, including 13,993 participants aged 18‒90 years who underwent KSHV serology evaluations. Mortality outcomes were ascertained through December 2019 using the National Death Index. Cox proportional hazards models were employed to examine the association between KSHV seropositivity and mortality, adjusting for potential confounders such as age, sex, ethnicity, body mass index, and serum TG. Over a median follow-up period of 26.5 years, 5503 deaths were recorded. KSHV seropositivity was associated with an increased hazard of all-cause mortality (Hazard Ratio [HR]: 1.32, 95% Confidence Interval [CI]: 1.03‒1.69) and cardiovascular mortality (HR: 1.58, 95% CI: 1.00‒2.50) after adjusting for age, sex, ethnicity, and body mass index. Notably, the association between KSHV infection and all-cause mortality persisted among women (HR: 1.32, 95% CI: 1.02‒1.72) after adjusting for all confounders, whereas the association with cardiovascular mortality was only statistically significant for men (HR: 1.90, 95% CI: 1.02, 3.53).KSHV infection may represent an independent risk factor for all-cause and cardiovascular mortality among US adults. These findings highlight the need for further research to validate these associations in independent populations and to elucidate the biological mechanisms underlying the observed increased mortality associated with KSHV infection.

Unveiling the causal link between herpes virus infection and cutaneous leukocytoclastic angiitis: Insights from Mendelian randomization analysis

AbstractBackgroundCutaneous leukocytoclastic angiitis (CLA) is a clinically relevant condition, with previous studies suggesting an association with herpes virus infections. However, the causality of this association remains unclear. This study aimed to investigate the causal relationship between herpes viruses and CLA.MethodsGenetic variants linked to the herpes virus were retrieved from the Integrative Epidemiology Unit at the University of Bristol open genome‐wide association studies project and FinnGen database. Data on CLA, involving 262 CLA cases and 207,482 healthy controls, were obtained from the FinnGen consortium R7. Mendelian randomization (MR) analysis, including the inverse variance weighted (IVW), MR‐Egger, and weighted median methods, was performed. Sensitivity analyzes were conducted to ensure the accuracy of the results.ResultsOf the 15 herpes viruses investigated, only human herpesvirus 6 (HHV‐6) demonstrated a causal association with CLA (odds ratio: 1.886, 95% confidence interval: 1.053–3.378, p = 0.033), indicating that HHV‐6 infection significantly increases the risk of CLA. Furthermore, IVW and MR‐Egger tests for heterogeneity confirmed homogeneous MR analysis results without evidence of horizontal pleiotropy (p &gt; 0.05). No significant causal relationship was observed for other herpes viruses, such as herpes simplex virus, varicella‐zoster virus, cytomegalovirus, and Epstein‐Barr virus.ConclusionOur MR analyzes strongly support a causal relationship between HHV‐6 and CLA, elucidating the etiology of this condition and highlighting the potential of HHV‐6‐targeted therapeutic interventions in CLA treatment. However, further research is necessary to expound the underlying mechanisms and explore potential therapeutic interventions targeting HHV‐6‐associated CLA.

Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

Clinical and immunological characteristics of post-covid patients with infectious immunopathology syndrome

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused global morbidity and high mortality worldwide. Today it is known that, despite recovery from COVID-19, confirmed by both laboratory and instrumental diagnostic methods, many patients, regardless of the severity of the disease, suffer from a significant deterioration in health and increased exacerbations of chronic diseases. During examinations by attending physicians, they note fatigue, an increase in cases of acute respiratory viral infections per year, an increase in relapses of skin diseases such as furunculosis, pyoderma, exacerbation of pulmonary pathologies, pathologies of the urinary tract of inflammatory origin, as well as chronic infectious diseases such as herpesvirus and human papillomavirus infections, which occur for the first time or are characterized by frequent relapses no less than six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome. SARS-CoV-2 infection is accompanied by damage to both the acquired and innate immune systems. In previous work, we determined the role of B cells, cytotoxic T lymphocytes, natural killer cells and the regulatory properties of CD46, as well as its involvement in the processes of viral entry into the cell. In this study, we studied the relationship of immune disorders of these factors of innate and acquired immunity with the clinical manifestations of post-COVID infectious syndrome in this category of patients and the severity of lung damage in these patients during the acute period of COVID-19. The results of the study showed that in some patients more than six months after suffering from COVID-19, the following was revealed: in patients who had a coronavirus infection without lung damage, no violations of the innate and acquired parts of the immune system were detected. In addition, significant differences were identified between clinical manifestations of diseases with increasing cases of relapses or newly identified after clinical recovery from an acute COVID-19 infection, depending on the phenotype of immune status disorders.

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights.

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Fatal infection caused by a genetically distinct elephant endotheliotropic herpesvirus type 5 in a captive Asian elephant in Germany

BackgroundElephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants.Case presentationHere we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence.ConclusionsWe have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures.

Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity.

Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.

Propagation of koi herpesvirus using embryonated chicken eggs: a potential substitute method for fish vaccine production?

Koi herpesvirus disease (KHVD) is caused by a large DNA virus that commonly infects carp, Cyprinus carpio (koi and common carp). KHVD has spread rapidly across the globe and caused high mortality in all ages of common carp and koi. Until now, no effective treatment has been applied to prevent KHV infection impacting the mass production of koi and common carp . An environmentally friendly alternative strategy for controlling fish disease is vaccination. One of the challenges facing conventional viral vaccine production is the requirement for koi or common carp cell cultures, which must be frequently maintained with expensive materials required for virus propagation. This study aims to obtain KHV that has been propagated in embryonated chicken eggs (ECE) to formulate an affordable KHV vaccine for the aquaculture industry. This research consisted of three stages; the first stage was virus inoculation into various parts of eggs (allantoic fluid, chorioallantoic membrane, amniotic fluid, and egg yolk). The second stage was observing viral growth and collecting ECE fluid and membranes. The third stage involved quantitatively determining the viral genomic copy numbers using the quantitative Polymerase Chain Reaction (qPCR) assay. KHV propagation in various parts of ECE resulted in varying viral genomic copy numbers with a high DNA copy number reported in allantoic fluid on the third day after inoculation. Further work is required to monitor virus titer in later passages and optimize methodology for using ECE as the potential alternative to cultured cells as the medium for virus propagation. In the future the system could be developed to produce promising vaccine candidates with more affordable vaccine prices for the Indonesian fish farming industry.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified DMD transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies. We used single-cell RNA-sequencing and T-cell receptor (TCR)-sequencing on peripheral blood mononuclear cells from five participants prior to, and after, dosing. One subject in the high-dose cohort experienced thrombotic microangiopathy (TMA). Few changes in cell frequencies occurred after treatment; however, differential gene expression demonstrated induction of interferon response genes in most T-cell types. T-cell clonotype and clumping analysis showed the expansion or appearance of groups of related TCR sequences in the post-treatment samples. Three of these expanded clumps could be assigned to prior Human Herpesvirus infections, two of which were present in the participant that exhibited TMA. These data provide insight on the mechanistic basis of human immune-AAV interactions and lay a foundation for improved understanding of why TMA arises in some patients and not others.

Kaposi Sarcoma in Two Lung Transplant Recipients: A Single-Center Experience

Kaposi's Sarcoma (KS) is a malignant vascular tumor commonly seen in immunocompromised individuals, particularly patients with acquired immunodeficiency syndrome. Lung transplant patients are at a high risk of developing KS due to a strong immunosuppressive regimen that can lead to donor-derived infection or reactivation of recipient human herpes virus - 8, the causative organism for KS. In this overview, we describe two recipients of lung transplants that developed pulmonary KS with poor outcomes. We review the diagnosis, bronchoscopy findings, treatment and surveillance strategies for pulmonary KS.

Dermatovenereology in the Russian Federation: results of 2023

The article presents information on dynamics of dermatovenerological service resources, indicators of the population of the Russian Federation provision with dermatovenerologists and dermatovenerological beds, main performance rates and results of dermatovenereological medical care providing in outpatient, inpatient and day hospital conditions for the period 2019–2023. The dynamics of sexually transmitted infections (syphilis, gonococcal infection, trichomoniasis, chlamydial infection, anogenital herpetic viral infection and anogenital venereal warts) incidence in the Russian Federation, as well as contribution of foreign citizens to the syphilis incidence rates are analyzed. The dynamics of prevalence and incidence rates of diseases of the skin and subcutaneous tissue in the Russian Federation in 2019–2023, as well as dynamics of prevalence and incidence of atopic dermatitis, psoriasis, contact dermatitis, localized scleroderma, discoid lupus erythematosus among children aged 0–17 years and adults 18 years and older are presented.

Causality between herpes virus infections and allograft dysfunction after tissue and organ transplantation: a two-sample bidirectional Mendelian randomization study.

Observational studies have suggested that herpes virus infections increase the risk of allograft dysfunction after tissue and organ transplantation, but it is still unclear whether this association is causal. The aim of this study was to assess the causal relationship between four herpes virus infections and allograft dysfunction. We used two-sample bidirectional Mendelian randomization (MR) to investigate the causality between four herpes virus infections - cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella zoster virus (VZV) - and allograft dysfunction after tissue and organ transplantation. Based on summary data extracted from genome-wide association studies (GWAS), we chose eligible single nucleotide polymorphisms (SNPs) as instrumental variables. The Inverse variance weighted (IVW) method was used as the main analysis method, supplemented by Weighted median and MR-Egger analyses. The MR-PRESSO test, MR-Egger intercept test, heterogeneity test, leave-one-out analysis and funnel plot were used to analyze the sensitivity of MR results. We found EBV early antigen-D (EA-D) antibody levels and shingles were the only two variables associated with an increased risk of allograft dysfunction. No evidence of allograft dysfunction increasing the risk of the four herpes virus infections was observed. Sensitivity analyses confirmed the robustness of our results. Our results suggest that EBV and VZV are involved in graft rejection or dysfunction. However, the relationship between CMV and HSV infections and allograft dysfunction remains unclear and requires further clarification.

The comprehensive evaluation and mechanism of HOUTTUYNIA CORDATA (Thunb) injection as a complementary therapy for infantile pneumonia

BackgroundHouttuynia cordata injection (HCI), a commercialized product made from the active ingredients extracted from Houttuynia cordata Thunb, has been used clinically in China for >50 years with significant therapeutic effects on pseudorabies herpesvirus infection in vitro and H1N1 influenza virus in mice. Purpose of studyThis work is to evaluate the complementary therapeutic effect of HCI on infantile pneumonia (IP) and to explore its mechanism of action. Study designFirst, the complementary efficacy of HCI in improving IP was evaluated by meta-analysis, with only randomized controlled trials from 5 electronic databases were included in this study. Second, network pharmacology was employed to predict the underlying mechanism of HCI in improving IP. Finally, molecular docking, surface plasmon resonance (SPR) and lipopolysaccharide (LPS)-induced rat IP model were used to verify the predicted results. ResultsMeta-analysis indicated that HCI can complementarily improve pneumonia by increasing cure rate and reducing the duration of fever, cough, and wheezing. Network pharmacology analysis using databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), Swiss target prediction, Therapeutic target database and Genecards showed that quercetin, houttuynin and kaempferol in HCI are the main compounds that improve IP and regulate 96 pneumonia-related protein targets. Protein-protein interaction (PPI) network analysis indicated that interleukin-6, tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), protein kinase B-1, matrix metalloproteinase 9, interleukin-10, tumor protein 53, epidermal growth factor receptor, C-X-C motif chemokine 8 and interferon gamma are the ten most relevant targets of HCI in improving IP. In the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, 96 targets are involved in 706 GO functions and 148 KEGG pathways. Among them, TNF-α/IL-1β signaling associated with inflammatory response is considered to be an important mechanism in IP. Molecular docking, SPR and LPS-induced IP model confirmed the predicted results. ConclusionsHCI has a complementary therapeutic effect on IP, and its mechanism may be related to the inhibition of TNF-α/IL-1β inflammatory response by two flavonoid compounds.

Changes in serum levels of pro- and anti-inflammatory cytokines in women with papillomavirus infection before and after therapy”

Papillomavirus infections (PVI) are among the most common sexually transmitted diseases in the young population. A long, sluggish inflammatory process sufficiently worsens adequate preparation for normal pregnancy. Herpesvirus and Chlamydia infections are the most frequent associations with papillomavirus infection. Many authors believe that PVI may cause dysregulation of pro- and anti-inflammatory cytokines revealed in blood serum. Currently, there are no uniform standards for management and treatment of women with papillomavirus infection without pronounced clinical manifestations, in order to prevent morphofunctional disorders of genitourinary system leading to reproductive disorders. However, most authors believe that antiviral and immunomodulatory drugs are the main tool of therapy against expansion of pathogens in the body. The aim of our study was to compare changes in the levels of IL-17, IL-12 p70, IL-12 p40, IL-13 and TGF-p1 in blood serum of women with papillomavirus infection before and after therapy with Inosine pranobex (IP) and Solanum tuberosum (ST). We conducted a survey of 137 patients with papillomavirus infection treated with drugs containing Inosine pranobex and Solanum tuberosum as active substances. The levels of IL-17, IL-12 p70, IL-12 p40, IL-13, and TGF-p1 in blood serum were determined using specific reagents from RD Diagnostics Inc. (USA). Changes in pro- and anti-inflammatory cytokines before therapy were as follows: decreased levels were found for IL-12 p70, p40; increased values were revealed for IL-13, IL-17, and TGF-p1. After the courses of therapy, we have registered the following changes in PVI-infected patients treated with synthetic drug Inosine pranobex (IP): the levels of IL-12 p70, IL-12 p40 were increased, along with decrease in IL-13 and TGF-p1. Meanwhile, ST therapy was associated with increase in IL-12 p70, IL-12 p40, and a decrease in IL-13 and TGF-p 1. With IP therapy, patients with combined HPV + HV infection showed an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13, while TGF-p1 did not change. Following ST therapy, these patients exhibited higher IL-12 p70, IL-12 p40, decreased IL-13, whereas TGF-p 1 remained unchanged. In the group of women with HPV + Chlamydia infection, an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p1 was associated with IP therapy. An increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p 1 were shown after ST therapy. In all groups of patients, IL-17 remained at high levels after therapy without significant differences between the mentioned subgroups. In the groups of patients treated with IP. we have recorded a general normalization of immune disorders.

Causal relationships of infection with Helicobacter pylori and herpesvirus on periodontitis: A Mendelian randomization study

BackgroundTo explore the causal association between Helicobacter pylori (H. pylori) infection, herpesvirus infection and periodontitis (PD) from a genetic perspective using Mendelian randomization (MR). MethodsThe PD data were derived from genome-wide association study (GWAS) from the Dental Endpoints (GLIDE) consortium, and the FinnGen Biobank provided data on H. pylori and herpesvirus infections. In addition, we examined GWAS data for subtypes of H. pylori and herpesvirus infection. Inverse variance weighting (IVW) was selected as a major analysis technique, and weighted median (WM), weighted model, simple model, and MR-Egger regression were added as supplementary methods. To verify the findings, the effects of pleiotropy and heterogeneity were assessed. ResultsGenetically predicted H. pylori infection (OR = 0.914, 95%CI = 0.693–1.205, P = 0.523), anti-H. pylori VacA (OR = 0.973, 95%CI = 0.895–1.057, P = 0.515), anti-H. pylori CagA (OR = 1.072, 95%CI = 0.986–1.164; P = 0.102), Epstein-Barr virus (EBV) infection (OR = 1.026, 95%CI = 0.940–1.120, P = 0.567), Herpes simplex virus (HSV) infection (OR = 0.962, 95%CI = 0.883–1.048, P = 0.372), cytomegalovirus (CMV) infection (OR = 1.025, 95%CI = 0.967–1.088, P = 0.415), EBV nuclear antigen-1 (EBNA1) (OR = 1.061, 95%CI = 0.930–1.209, P = 0.378), EBV virus capsid antigen (VCA) (OR = 1.043, 95CI% = 0.890–1.222, P = 0.603), HSV-1 (OR = 1.251, 95%CI = 0.782–2.001, P = 0.351), HSV-2 (OR = 1.020, 95%CI = 0.950–1.096, P = 0.585), CMV IgG (OR = 0.990, 95CI% = 0.882–1.111, P = 0.861) were not associated with PD, indicated that H. pylori and herpesvirus infection had no causal relationship to PD. Reverse studies also found no cause effect of PD on H. pylori or herpesvirus infection. The results of the sensitivity analysis suggested the robustness of the MR results. ConclusionThis study offered preliminary proof that H. pylori and herpesvirus infections were not causally linked to PD, and vice versa. However, more robust instrumental variables (IVs) and larger samples of GWAS data were necessary for further MR analysis.