Carotane sesquiterpenes from Peperomia pellucida and their anti-infective activities.

Owing to the challenges of antimicrobial resistance, investigations of new antibiotics from medicinal plants are continuously being conducted. Peperomia pellucida is a pantropical plant used in traditional medicine for the treatment of various disorders. From the ethanol extract of a whole P. pellucida plant, one previously undescribed carotane sesquiterpene (pellucarotine), one known carotane sesquiterpene (daucol), and one phenylpropanoid (dillapiol) were isolated and structurally elucidated. Their structures were determined based on 1D and 2D NMR, HR-ESI-Mass, experimental, and computational electronic circular dichroism spectroscopic data and compared with those reported in the literature. Antimicrobial assay results showed that pellucarotine had an anti-infective effect on Candida albicans with an MIC of 512 µg/mL.

Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study.

The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.

Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study.

Introduction: Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods: Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results: The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion: The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.

MyD88 modulates eosinophil and neutrophil recruitment as well as IL-17A production during allergic inflammation.

The contribution of dysregulated innate immune responses to the pathogenesis of allergic disease remains largely unknown. Herein, we addressed the role of Toll-like receptor signaling in airway inflammation by studying mice rendered deficient for the myeloid differentiation factor 88 (MyD88-/-) which results in concurrent deficiencies in TLR and IL-1R1 signaling pathways. We show that the lack of MyD88 offers a partial protection from allergic disease evidenced by reduced airway eosinophilia and production of the Th17-associated effector cytokine IL-17A. By contrast, airway hyperreactivity and Th2 cytokine production, the cardinal features of allergic disease, remained unchanged. We found that the impaired IL-17A production in MyD88-/- mice was associated with defective CD4+ T cells, which failed to respond to IL-23 stimulation. The total number of Th17-associated effectors in lymph nodes was likewise decreased. Taken together, our results demonstrate that MyD88-dependent mechanisms are critical for orchestrating lung inflammatory responses, in terms of IL-17A production, as well as eosinophil and neutrophil recruitment.

Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR) stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA)-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD) that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses. They provide a plausible explanation for the hygiene hypothesis. They also open new therapeutic perspectives for the prevention of these pathologies.

Ginger prevents Th2-mediated immune responses in a mouse model of airway inflammation.

It is well documented that compounds from rhizomes of Zingiber officinale, commonly called ginger, have anti-inflammatory properties. Here, we show that ginger can exert such functions in vivo, namely in a mouse model of Th2-mediated pulmonary inflammation. The preparation of ginger aqueous extract (Zo.Aq) was characterized by mass spectrometry as an enriched fraction of n-gingerols. Intraperitoneal injections of this extract before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in the recruitment of eosinophils to the lungs as attested by cell counts in bronchoalveolar lavage (BAL) fluids and histological examination. Resolution of airway inflammation induced by Zo.Aq was accompanied by a suppression of the Th2 cell-driven response to allergen in vivo. Thus, IL-4, IL-5 and eotaxin levels in the lungs as well as specific IgE titres in serum were clearly diminished in ginger-treated mice relative to their controls after allergen sensitization and challenge. Finally, we found that [6]-gingerol, a major constituent of ginger, was sufficient to suppress eosinophilia in our model of inflammation. This is the first evidence that ginger can suppress Th2-mediated immune responses and might thus provide a possible therapeutic application in allergic asthma.

Morbidity status in Nam Dong district hospital, Thua Thien - Hue province during 3 years from 2000 to 2002

The study carried on 6122 patients hospitalized in Nam Dong district hospital, Hue province from 2000 to 2002. The results were ranked according to proportion morbidity by disease chapter of ICD 10: Most common ten diseases were diseases of the respiratory system, accidents injury, poisoning, infectious and parasitic, pregnancy, delivery and puerperium, disease of digestive system, disease of the genitourinary system, disease of the musculoskeletal system, disease of the circulatory system, disease of the skin and subcutaneous system, disease of the nervous system. Major cause of morbidity in children under 15 years old were respoiratory and infectious disease. 15 to 19 group mainly hospitalized due to accidents, injury and poisoning. Over 60 group primary hospitalized due to respiratory system, disgestive system, circulatory system, infectious and parasitic diseases

Study on infiltrated lymphocytes in lung cancer

73 cases of lung cancer were studied at the Institute of Tuberculosis and Lung diseases. The infiltration of lymphocytes in the tissue of primary lung cancer in operation was investigated. HE staining method was used, 47 cases stained by immunochemicals with antiCD3, CD20, CD8 antibodies. Lymphoid infiltration was observed in 64% of cancer tissues, among them 42,5% of cases there is a infiltration of high level lymphoid infiltration was identified in chorial tissues and intertialis tissues. The form of cyste was localized only in chorial tissue.