Anticancer potential of ß-sitosterol and oleanolic acid as through inhibition of human estrogenic 17beta-hydroxysteroid dehydrogenase type-1 based on an in silico approach.

The human estrogenic enzyme 17beta-hydroxysteroid dehydrogenase type-1 (HSD17B1) provides biosynthesis regulation of active estrogen in stimulating the development of breast cancer through cell proliferation. The ß-sitosterol is classified as a steroid compound and is actually a type of triterpenoid compound that has a similar structure to a steroid. This similarity provides a great opportunity for the inhibitor candidate to bind to the HDS17B1 enzyme because of the template similarity on the active site. Several in silico approaches have been applied in this study to examine the potential of these two inhibitor candidates. Pharmacokinetic studies showed positive results by meeting several drug candidate criteria, such as drug-likeness, bioavailability, and ADMET properties. A combination of molecular docking and MD simulation showed good conformational interaction of the inhibitors and HSD17B1. Prediction of binding free energy (ΔG bind) using the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) approach shows ΔG bind (kcal mol-1) of C1-HSD17B1: -49.31 ± 0.23 and C2-HSD17B1: -33.54 ± 0.34. Meanwhile, decomposition energy analysis (ΔG residue bind) suggested several key residues that were also responsible for the interaction with inhibitors, such as C1-HSD17B1 (six residues: Leu96, Leu149, Pro187, Met193, Val225, and Phe226) and C2-HSD17B1 (four residues: Ile14, Gly94, Pro187, and Val188). Hopefully, the obtained results from this research could be considered for the mechanistic inhibition of the HSDS17B1 enzyme at molecular and atomistic levels.

Adverse Drug Reactions in Selected Wards of the Yangon General Hospital and Yangon Specialty Hospital During the First Quarter of 2019: An Active Pharmacovigilance Study in Myanmar.

BACKGROUND: Previous studies in Europe and the USA have reported a high prevalence of adverse drug reactions (ADRs), but data on local ADRs in Myanmar are sparse. OBJECTIVE: Our objective was to study ADRs in patients admitted to selected wards of Yangon General Hospital (YGH) and Yangon Specialty Hospital (YSH), Myanmar. METHODS: This was a prospective observational study in three hospital wards during the first quarter of 2019. Suspected ADRs were carefully investigated in a face-to-face interview with each patient and via review of clinical records. Patients transferred to other wards or discharged were followed-up by the researchers until day 28 after admission. ADRs were divided into those that (1) led to the admission and (2) occurred during the hospital stay or after discharge (up to day 28 after admission). RESULTS: A total of 65 ADRs were identified, with 47 (29.4%) of 160 patients experiencing at least one ADR. Among these, 16 (24.6%) had led to hospital admission and 49 (75.4%) occurred in 31 patients during their hospital stay. Of 160 patients, 21 had taken at least one herbal remedy and six of these developed an ADR. Five ADR-drug associations (hypokalaemia with methylprednisolone, increased transaminase levels with standard antituberculosis drugs, upper gastrointestinal bleeding with nonsteroidal anti-inflammatory drugs, constipation with tramadol, and increased transaminase levels with herbal remedies) represented 18 (27.7%) of the 65 ADRs in this study. According to the Schumock and Thornton preventability scale, more than half of these ADRs (35 [53.9%]) were preventable. CONCLUSION: The present study highlights the existence of ADRs among patients attending these hospitals. The implementation of active pharmacovigilance in hospitals could be a helpful first step to improving the awareness of unwanted effects of medicines and patient safety, as well as a way to strengthen the national pharmacovigilance system in countries such as Myanmar.

The Green Revolution shaped the population structure of the rice pathogen Xanthomonas oryzae pv. oryzae.

The impact of modern agriculture on the evolutionary trajectory of plant pathogens is a central question for crop sustainability. The Green Revolution replaced traditional rice landraces with high-yielding varieties, creating a uniform selection pressure that allows measuring the effect of such intervention. In this study, we analyzed a unique historical pathogen record to assess the impact of a major resistance gene, Xa4, in the population structure of Xanthomonas oryzae pv. oryzae (Xoo) collected in the Philippines in a span of 40 years. After the deployment of Xa4 in the early 1960s, the emergence of virulent pathogen groups was associated with the increasing adoption of rice varieties carrying Xa4, which reached 80% of the total planted area. Whole genomes analysis of a representative sample suggested six major pathogen groups with distinctive signatures of selection in genes related to secretion system, cell-wall degradation, lipopolysaccharide production, and detoxification of host defense components. Association genetics also suggested that each population might evolve different mechanisms to adapt to Xa4. Interestingly, we found evidence of strong selective sweep affecting several populations in the mid-1980s, suggesting a major bottleneck that coincides with the peak of Xa4 deployment in the archipelago. Our study highlights how modern agricultural practices facilitate the adaptation of pathogens to overcome the effects of standard crop improvement efforts.

Years of healthy life lost due to adverse pregnancy and childbirth outcomes among adolescent mothers in Thailand.

BACKGROUND: Preventing adolescent pregnancy and childbirth is one of the targets of Sustainable Development Goals. Measuring the burden pregnancy and childbirth places on adolescents is required to convince society and decision makers that this is an important goal. OBJECTIVE: This study aimed to estimate (1) the years of healthy life lost due to adolescent pregnancy and childbirth in terms of disability adjusted life years (DALYs), (2) the contribution of adolescent pregnancy and childbirth to the total DALYs lost from all reproductive ages, and (3) the magnitude of the burden due to five main direct obstetric causes and sequelae in adolescent mothers in Thailand in 2014. METHODS: Data were retrieved from a national in-patient registered database and a vital registration database. Health consequences of five main direct obstetric causes were extracted from the Global Burden of Diseases (GBD) 2000 study. The DALYs were calculated by the combination of Years of Life Lost (YLL) due to premature death and Years Lived with Disability (YLD) due to adverse pregnancy and childbirth in adolescent mothers. RESULTS: There were a total of 2599 years of DALYs lost from the consequences of adolescent pregnancy and childbirth, and unsafe abortion resulted in the highest burden. Mortality was the primary driver for the total DALYs lost with 1704 years, and maternal hemorrhage dominated in the total YLL. Unsafe abortion contributed the highest burden to nonfatal morbidity. Obstructed labor commonly occurred in adolescent pregnancies. CONCLUSION: Among the DALYs lost due to pregnancy and childbirth for all reproductive aged women, 15.4% were attributed to adolescents. The five main obstetric causes of mortality and morbidity are all preventable conditions. Increased efforts from all stakeholders are essential to implement appropriate interventions to minimize adverse health outcomes in adolescent mothers.

Effectiveness of three oral hygiene regimens on oral malodor reduction: a randomized clinical trial.

BACKGROUND: Breath odor is a nuisance problem for many people around the world. Bad breath affects social interactions of people in daily life by causing personal discomfort and emotional stress. There are chemical and mechanical methods for controlling oral malodor. Many studies of various mouth rinse applications and tongue cleaning procedures have been conducted. However, few studies have compared the effect of simultaneous chemical and mechanical procedures on the reduction of volatile sulfur compounds (VSCs) in subjects with oral malodor. The purpose of this study was to assess the effects of different oral hygiene procedures on reduction of VSCs in subjects with oral malodor. METHODS: Thirty male volunteers who matched with study criteria were divided randomly into two groups. Both groups performed tooth brushing, mouth washing with chlorine dioxide, tongue cleaning and combination of those in different sequence for five weeks. Total VSCs of subjects were measured with a Breathtron®, and oral health status was also examined. Quantitative analyses were performed using the Statistical Package for Social Science (SPSS 16.0). RESULTS: There were no significant differences in oral health status between the two groups at the baseline. No significant decrease in oral malodor was detected after one week of tooth brushing. Significant reductions in VSCs were shown by adding mouthwash or tongue cleaning to tooth brushing from the second week to fourth week (P <0.01). The greatest reduction in VSCs was found at the fifth week after the practice of all three oral hygiene regimens. CONCLUSIONS: Tooth brushing alone does not significantly reduce oral malodor. Mouth washing and tongue cleaning significantly reduce oral malodor, but combining tooth brushing, mouth washing and tongue cleaning regimens is most effective for oral malodor reduction. The results of this study could contribute to the formulation of appropriate preventive strategies against oral malodor not only for the general public but also for dental professionals serving as oral malodor-related service providers. TRIAL REGISTRATION: Registration number - ClinicalTrials.gov NCT02113137 . Registration date - April 7th, 2014.