Network pharmacology and molecular docking technology for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba herb-pair on anti-hepatitis: A review.

The Radix Bupleuri and Radix Paeoniae Alba herb-pair (RRH) are the most classic compatible drug pair for the treatment of hepatitis. However, the underlying mechanism remains unclear. Therefore, network pharmacology and molecular docking were conducted to investigate the prospective therapeutic constituents, targets, and pharmacological mechanisms of RRH in the treatment of hepatitis. The active components of RRH from the TCMSP database and disease-related targets from the OMIM, PharmGkb, GeneCards, TTD, and DrugBank databases were identified. The "drug-target-disease" network diagram and protein-protein interaction (PPI) network were constructed using Cytoscape (v3.8.0) and Online STRING 11.0. GO and KEGG pathway enrichment analyses were performed using R version 4.1.2, and molecular docking was performed to verify the results. We placed 176 overlapping cross genes into Online STRING 11.0 and obtained 14 core targets. A "Component-Target-GO-KEGG" network diagram was constructed, which was composed of 7 components, 14 targets, 10 biological processes, and 10 signal pathways. A total of 2413 GO biological processes and 174 KEGG pathways were explored for hepatitis treatment. Quercetin, kaempferol, isorhamnetin, and beta-sitosterol, which are the main bioactive components, were employed to bind the disease's hub targets, ensuring fulfillment of spatial and energy matching. The anti-hepatitis mechanism of RRH may be associated with several targets including RELA, AKT1, JUN, MAPK1, TP53, CCND1, MYC, NFKBIA, CDKN1A, and their respective signaling pathways. The main bioactive components in RRH, including quercetin, kaempferol, isorhamnetin, and beta-sitosterol, were used to bind the hub targets of the disease, which may provide insights into drug development for hepatitis.

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells.

BACKGROUND: Traditional Chinese medicine has used the drug Pien Tze Huang (PTH), a classic prescription, to treat autoimmune hepatitis (AIH). However, the precise mode of action is still unknown. AIM: To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T (mTreg) cells functional levels. METHODS: Following induction of the AIH mouse model induced by Concanavalin A (Con A), prophylactic administration of PTH was given for 10 d. The levels of mTreg cells were measured by flow cytometry, and intestinal microbiota was analyzed by 16S rRNA analysis, while western blotting was used to identify activation of the toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways. RESULTS: In the liver of mice with AIH, PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-2, IL-6, and IL-21 expression. Simultaneously, PTH stimulated the abundance of helpful bacteria, promoted activation of the TLR2 signal, which may enhance Treg/mTreg cells quantity to produce IL-10, and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways. CONCLUSION: PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study.

The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.

Drug Screening for Hepatitis A Virus (HAV): Nicotinamide Inhibits c-Jun Expression and HAV Replication.

Hepatitis A virus (HAV) infection often causes acute hepatitis, which results in a case fatality rate of 0.2% and fulminant hepatitis in 0.5% of cases. However, no specific potent anti-HAV drug is available on the market to date. In the present study, we focused on inhibition of HAV internal ribosomal entry site (IRES)-mediated translation and investigated novel therapeutic drugs through drug repurposing by screening for inhibitors of HAV IRES-mediated translation and cell viability using a reporter assay and cell viability assay, respectively. The initial screening of 1,158 drugs resulted in 77 candidate drugs. Among them, nicotinamide significantly inhibited HAV HA11-1299 genotype IIIA replication in Huh7 cells. This promising drug also inhibited HAV HM175 genotype IB subgenomic replicon and HAV HA11-1299 genotype IIIA replication in a dose-dependent manner. In the present study, we found that nicotinamide inhibited the activation of activator protein 1 (AP-1) and that knockdown of c-Jun, which is one of the components of AP-1, inhibited HAV HM175 genotype IB IRES-mediated translation and HAV HA11-1299 genotype IIIA and HAV HM175 genotype IB replication. Taken together, the results showed that nicotinamide inhibited c-Jun, resulting in the suppression of HAV IRES-mediated translation and HAV replication, and therefore, it could be useful for the treatment of HAV infection. IMPORTANCE Drug screening methods targeting HAV IRES-mediated translation with reporter assays are attractive and useful for drug repurposing. Nicotinamide (vitamin B3, niacin) has been shown to effectively inhibit HAV replication. Transcription complex activator protein 1 (AP-1) plays an important role in the transcriptional regulation of cellular immunity or viral replication. The results of this study provide evidence that AP-1 is involved in HAV replication and plays a role in the HAV life cycle. In addition, nicotinamide was shown to suppress HAV replication partly by inhibiting AP-1 activity and HAV IRES-mediated translation. Nicotinamide may be useful for the control of acute HAV infection by inhibiting cellular AP-1 activity during HAV infection processes.

Bioactive compounds from Pandanous fascicularis as potential therapeutic candidate to tackle hepatitis a inhibition: Docking and molecular dynamics simulation study.

Due to extensive pharmacological research, medicinal plants the underpinning of indigenous herbal serve as a possible source of key compounds for the development of new drugs. Hepatitis A, one of the most widespread infectious diseases associated with global public health issues. The transmission of hepatitis A virus (HAV) occurs, through personal contact, as well as contaminated food/water. The HAV 3C cysteine protease is a non-structural protein, plays pivotal role in proliferation and viral replication. Significant phytochemicals of Pandanous fascicularis include phytosterol, kobusin, epipinoresinol, and ceroptene, which have a wide variety of biological functions. Through ADMET investigation, we have screened fifteen phytochemicals for this study. Additionally, using molecular docking, these phytochemicals were docked with the HAV 3C protease which signifies the phytochemicals phytosterol, kobusin, epipinoresinol, and ceroptene have a significant capability to bind with hepatitis A virus protein.The docking study was further accompanied by analyzes RMSD, RMSF, Rg, SASA, H-bond number, and principal component analysis through 100 ns MD simulations. The molecular dynamics study reveals that, all four phytochemicals possess considerable binding efficacy with hepatitis A virus protein. Based on our computational study and MMGBSA calculations, phytosterol, kobusin and epipinoresinol phytochemicals may be a potential drug candidate for inhibition of hepatitis A. The potential therapeutic characteristics of the phytochemicals against hepatitis A inhibition offer additional support for the in vitro and in vivo studies in future.Communicated by Ramaswamy H. Sarma.

Acute hepatitis in a paediatric patient: immune-mediated drug-induced liver injury or albendazole-induced autoimmune hepatitis?

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity. CASE REPORT: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up. CONCLUSIONS: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population.

Setting up criteria for drug-induced autoimmune-like hepatitis through a systematic analysis of published reports.

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms "drug-induced liver injury," "autoimmune hepatitis," and "drug-induced autoimmune hepatitis." DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs.

Predictors of hepatitis A immunity in adults in California in order to better utilize hepatitis A vaccine.

BACKGROUND: Hepatitis A vaccine recommendations now include homelessness, illegal drug use, and HIV, as well as traditional risk factors and travel to areas endemic for hepatitis A. We examined a large diverse population for predictors of Hepatitis A immunity in order to better utilize Hepatitis A vaccine. METHODS: We performed a cross-sectional descriptive study of members of a large integrated health plan with a test for Hepatitis A Immunoglobulin G (IgG) between January 1st, 2007, and December 31st, 2017. Exclusion criteria included age <18 years, <6 months of continuous enrollment, and Hepatitis A vaccine prior to Hepatitis A test. Variables of interest were age, gender, primary language spoken, ethnicity/race, neighborhood household income, and history of travel or history of jaundice. Multivariable logistic regression was performed to evaluate the association of risk factors on Hepatitis A immunity. RESULTS: Of the 318,170 persons ≥ 18 years tested for Hepatitis A immunity, 155, 842 persons had a reactive Hepatitis A IgG test (49%). The lowest prevalence was for Whites at 28.1% followed by Blacks at 35.8%. Hispanics and Asian/Pacific Islanders had prevalence rates of 63% and 68.2% respectively. In adjusted analyses, Asian/Pacific Islanders, Hispanics and Blacks were 5.17, 3.44 and 1.42 times more likely to have Hepatitis A immunity than Whites. Those that spoke Spanish or language other than English or Spanish as their primary preferred language were 6.11 and 3.27 time more likely to have immunity than English speakers. Known travel history conferred a 2.16 likelihood of Hepatitis A immunity. CONCLUSIONS: Persons of Hispanic and Asian/Pacific Islander background as well as persons with a preferred spoken language other than English have a high prevalence of Hepatitis A immunity. Testing for Hepatitis A immunity prior to vaccination should be considered for these groups.

Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies in inflammatory intestinal disease and rheumatoid arthritis. Prevention strategies. / Riesgo de infección asociado a los inhibidores de las quinasas Janus (JAK) y las terapias biológicas en enfermedad inflamatoria intestinal y artritis reumatoide. Estrategias de prevención.

Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.

Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection.

Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.

A comparative study on flavour components and therapeutic properties of unfermented and fermented defatted soybean meal extract.

Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 µg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.

Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus.

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.

Aspects épidémiologiques, cliniques, étiologiques et évolutifs des hépatites aiguës au Centre Hospitalier National d'Enfants Albert Royer-Dakar

Introduction : l'hépatite aiguë est fréquente et représente un problème de santé publique dans les pays en développement. Les étiologies sont dominées par l'hépatite A en Afrique subsaharienne et en Asie du Sud-Est. Cependant, très peu d'études locales ont porté sur cette pathologie. Objectif : Étudier les aspects épidémiologiques, cliniques et évolutifs des hépatites aiguës chez les enfants hospitalisés au CHNEAR. Matériel et Méthodes : il s'agissait d'une étude rétrospective réalisée au CHNEAR de Dakar du 1er janvier 2007 au 31 décembre 2017. Étaient inclus les enfants hospitalisés pour une hépatite aiguë. Les données socio démographiques, cliniques, paracliniques et évolutives ont été recueillies. L'analyse des données uni et bivariée était faite grâce au logiciel R studio version 3.5.0. Résultats : au total, 35 000 enfants étaient hospitalisés durant la période d'étude parmi lesquels 71 patients avaient une hépatite aiguë déterminant une prévalence hospitalière de 0,2%. L'âge moyen à l'admission était de 65 mois avec un sex-ratio de 1,5. L'ictère cutanéo-muqueux était le principal signe physique (81,7%). La cytolyse était constante avec une moyenne des ALAT de 549UI/L. Une insuffisance hépatocellulaire était notée chez 24% des patients. L'étiologie était dans la grande majorité des cas indéterminée (66,2%). L'hépatite A représentait 15,5% et la phytothérapie (18,3%). L'évolution était favorable dans l'ensemble sans aucun cas de rechute. La létalité était de 16,9%. Conclusion : l'étiologie des hépatites demeurent encore indéterminées dans une large proportion au CHNEAR de Dakar. Le pronostic reste réservé pour les formes graves avec insuffisance hépatocellulaire

Inhibitory effect of Japanese rice-koji miso extracts on hepatitis A virus replication in association with the elevation of glucose-regulated protein 78 expression.

Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis and acute liver failure in developing and developed countries. Although effective vaccines for HAV infection are available, outbreaks of HAV infection still cause deaths, even in developed countries. One approach to control HAV infection is prevention through diet, which can inhibit HAV propagation and replication. Glucose-regulated protein 78 (GRP78) is a member of the heat shock protein 70 family of molecular chaperone required for endoplasmic reticulum stress and stress-induced autophagy. We previously showed that the elevation of GRP78 expression inhibits HAV replication. It has been reported that Japanese miso extracts, which was made from rice-koji, enhance GRP78 expression. In the present study, we used human hepatoma Huh7 cells and human hepatocyte PXB cells to examine the efficacy of Japanese miso extracts as antiviral agents against HAV. Japanese miso extracts enhanced GRP78 expression and inhibited HAV replication in human hepatocytes. Together, these results demonstrate that Japanese miso extracts may partly modulate GRP78 expression and additively or synergistically work as antivirals against HAV infection. Japanese miso extracts can be used as effective dietary supplements for severe hepatitis A.

Recent epidemiology of sexually transmissible enteric infections in men who have sex with men.

PURPOSE OF REVIEW: Sexual transmission of enteric pathogens in men who have sex with men (MSM) has been described since the 1970s. Recently, an increasing number of enteric infection outbreaks have been reported in MSM. This article summarizes recent outbreaks and discusses the key issues for prevention and control. RECENT FINDINGS: Sexually transmissible enteric infections (STEIs) can spread rapidly and internationally within highly connected MSM populations and are often associated with antimicrobial resistance (AMR). The infections often cluster in high-risk groups of HIV-positive MSM who are more likely to engage in diverse sexual practices and chemsex, and to have multiple other sexually transmitted infections (STIs). SUMMARY: The roles of asymptomatic and/or persistent infection and other contextual factors in STEI transmission are not well described. STEI-associated AMR is increasing and has potential to spread rapidly in MSM, warranting further public health attention. A better understanding of the factors associated with sexual transmission will enable the development of more effective control measures. A holistic approach that promotes health and wellbeing as well as infection prevention and management is needed.

Development of a fast and efficient method for hepatitis A virus concentration from green onion.

Hepatitis A virus (HAV) can cause serious liver disease and even death. HAV outbreaks are associated with the consumption of raw or minimally processed produce, making it a major public health concern. Infections have occurred despite the fact that effective HAV vaccine has been available. Development of a rapid and sensitive HAV detection method is necessary for an investigation of an HAV outbreak. Detection of HAV is complicated by the lack of a reliable culture method. In addition, due to the low infectious dose of HAV, these methods must be very sensitive. Current methods rely on efficient sample preparation and concentration steps followed by sensitive molecular detection techniques. Using green onions which was involved in most recent HAV outbreaks as a representative produce, a method of capturing virus particles was developed using carboxyl-derivatized magnetic beads in this study. Carboxyl beads, like antibody-coated beads or cationic beads, detect HAV at a level as low as 100 pfu/25g of green onions. RNA from virus concentrated in this manner can be released by heat-shock (98°C 5min) for molecular detection without sacrificing sensitivity. Bypassing the RNA extraction procedure saves time and removes multiple manipulation steps, which makes large scale HAV screening possible. In addition, the inclusion of beef extract and pectinase rather than NP40 in the elution buffer improved the HAV liberation from the food matrix over current methods by nearly 10 fold. The method proposed in this study provides a promising tool to improve food risk assessment and protect public health.

Immune-Stimulatory and Therapeutic Activity of Tinospora cordifolia: Double-Edged Sword against Salmonellosis.

The present study was aimed at determining the activity of aqueous and methanolic extracts of Tinospora cordifolia (AETC and METC) against Salmonella typhimurium. In vitro anti-Salmonella activity of T. cordifolia was determined through the broth dilution and agar well diffusion assays. The immune-stimulating potential of AETC or METC was determined by measuring the cytokine levels in the culture supernatants of treated murine J774 macrophages. Antibacterial activity of AETC or METC was determined by treating S. typhimurium-infected macrophages and BALB/C mice. The toxicity of AETC or METC was determined by measuring the levels of liver inflammation markers aspartate transaminase (AST) and alanine transaminase (ALT) and antioxidant enzymes. Macrophages treated with AETC or METC secreted greater levels of IFN-γ, TNF-α, and IL-1ß. METC showed greater activity against S. typhimurium infection in macrophages and mice as well. Treatment with METC resulted in increased survival and reduced bacterial load in S. typhimurium-infected mice. Moreover, METC or AETC treatment reduced the liver inflammation and rescued the levels of antioxidant enzymes in S. typhimurium-infected mice. The results of the present study suggest that the use of T. cordifolia may act as a double-edged sword in combating salmonellosis.

Age-period-cohort analysis of hepatitis A incidence rates in Korea from 2002 to 2012.

OBJECTIVES: This study aimed to evaluate the epidemiology of hepatitis A in Korea from 2002 to 2012 using age-period-cohort analyses. METHODS: We used claims data from the Korean National Health Insurance Corporation for the entire population. Census data from 2010 were used as the standard population. The incidence of hepatitis A was assumed to have a Poisson distribution, and the models and effects were evaluated using the intrinsic estimator method, the likelihood ratio, and the Akaike information criterion. RESULTS: The incidence of hepatitis A gradually increased until 2007 (from 17.55 to 35.72 per 100,000 population) and peaked in 2009 (177.47 per 100,000 population). The highest incidence was observed among 27-29-year-old individuals when we omitted data from 2005 to 2007. From 2005 to 2007, the peak incidence was observed among 24-26-year-old individuals, followed by 27-29-year-olds. The best model fits were observed when the age-period-cohort variables were all considered at the same time for males, females, and the whole population. CONCLUSIONS: The incidence of hepatitis A exhibited significant age-period-cohort effects; its incidence peaked in 2009 and was especially high among Koreans 20-39 years of age. These epidemiological patterns may help predict when high incidence rates of hepatitis A may occur in developing countries during their socioeconomic development.