A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells.

BACKGROUND: Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. METHODS: Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24-/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-ß-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. RESULTS: Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. CONCLUSION: MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

Prevalence and determinants of TB infection in a rural population in northeastern Myanmar.

BACKGROUND: Tuberculosis (TB) is a major human threat, as evidenced by the large numbers of cases and deaths, particularly in developing countries with poor economic and educational statuses. Myanmar has one of the highest TB burdens in the world, but no TB information is available for people living in the rural northeastern regions of Myanmar. The present study estimated the prevalence of TB and identified factors associated with TB infection in people living in rural communities in Shan State. METHODS: A cross-sectional study was performed to gather information from participants. People aged 18-59 years who lived in the three areas with the highest numbers of TB cases in Shan State in northeastern Myanmar were included in the study population. A simple random method was used to select the sample from the villages. A validated questionnaire was used for data collection in face-to-face interviews after obtaining signed informed consent from the selected participants. The Mantoux tuberculin skin test (TST) was administered to detect TB infection, and a result that was 10 mm or greater after 48 h was considered positive. Chi-squared tests and logistic regression were used to identify the associations between the variables at a significance level of α = 0.05. RESULTS: A total of 303 participants were recruited for the study; 64.7% were females, and the mean age was 37 years (SD = 12.5). Most participants were Burmese (25.4%), and 14.95% were Shan. Sixty-three participants (20.8%) had a positive TST. Four variables were associated with TB infection in the multivariate model. Males had a greater chance of TB infection than females (AOR = 2.51; 95% CI = 1.32-4.76). Participants who were ever married had a greater chance of TB infection than participants who were single (AOR = 3.93; 95% CI = 1.18-13.00). Participants who used wood and charcoal as their main sources of energy for cooking had a greater chance of TB infection than participants who used electricity (AOR = 4.23; 95% CI = 1.25-9.64). Participants who had a low level of TB prevention and care knowledge had a greater chance of TB infection than participants with a high level of TB prevention and care knowledge (AOR = 4.49; 95% CI = 1.88-10.72). CONCLUSIONS: Public health programs that focus on improving knowledge of TB prevention and care and avoiding the use of wood and charcoal as the primary sources of energy for cooking, particularly in males and ever-married individuals, are urgently needed.

Factors associated with different forms of alcohol use behaviors among college students in Bhutan: a cross-sectional study.

BACKGROUND: Alcohol use has impacts on several dimensions of health, including physical health and mental health, particularly in college-age populations. Therefore, this study aimed to estimate the prevalence and to determine factors associated with alcohol use behaviors among college students in Bhutan. METHODS: A cross-sectional design was applied to collect data from the participants. A simple random method was used to select the participants from the lists of students who were attending the four selected colleges in Bhutan in the academic year of 2019. A questionnaire was developed, and validity and reliability were verified before use. Descriptive statistics were applied to describe the general characteristics of participants, while logistic regression was used to detect the associations between variables at the significance level of α = 0.05. RESULTS: A total of 432 college students were recruited into the study, of whom 62.0% were females. The average age was 20.0 years, 40.7% were the third-year students, and 79.9% lived in college dormitories. The prevalence of current drinking was 51.6% and that of binge drinking was 19.4%. After controlling for all potential confounder factors, three variables were found to be associated with current drinking: students who had low income were more likely to be current drinkers than those who had high income (AOR = 2.59, 95% CI = 1.29-5.21); students who did not use tobacco were more likely to be current drinkers than those students who used tobacco (AOR = 6.99, 95% CI = 2.90-16.81); and students who had close friends who did not use alcohol were more likely to be current drinkers than those who had close friends who used alcohol (AOR = 5.14, 95% CI = 3.04-8.69). Four factors were found to be associated with binge drinking after controlling for all possible confounder factors: students who had high income were more likely to be binge drinkers than those who had low income (AOR = 3.03, 95% CI = 1.72-5.31); students who used tobacco were more likely to be binge drinkers than those students who did not use tobacco (AOR = 2.28, 95% CI = 1.35-3.87); students whose parents used alcohol were more likely to be binge drinkers than those students whose parents did not use alcohol (AOR = 1.75, 95% CI = 1.02-3.01); and students whose close friends used alcohol were more likely to be binge drinkers than those who had close friends who did not use alcohol (AOR = 2.26, 95% CI = 1.05-4.87). CONCLUSIONS: There is a high prevalence in alcohol use among the college students in Bhutan. Effective health promotion programs should be implemented by focusing on reducing the alcohol consumption among college students.

Molecular epidemiology and clinical features of hand, foot and mouth disease in northern Thailand in 2016: a prospective cohort study.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a major communicable disease in children ≤6 years old, particularly in several countries in the Asia-Pacific Region, including Thailand. HFMD impacts public health and the economy, especially in northern Thailand. METHODS: A prospective cohort study was conducted to estimate the incidence rate and to identify the serotype and clinical features of HFMD among children in northern Thailand. A validated questionnaire and throat swab were used for data collection. Polymerase chain reaction (PCR) was used to detect human enterovirus and identify its serotypes. Participants were recruited from 14 hospitals in two provinces in northern Thailand, specifically, Chiang Rai and Pha Yao Province, between January 1, 2016, and December 31, 2016. Chi-square or Fisher's exact test was used to detect the associations of signs and symptoms with HFMD serotype. Logistic regression was used to detect the associations of variables with a positive enterovirus at alpha = 0.05. RESULT: In total, 612 children aged ≤6 years from Chiang Rai and Pha Yao Province who were diagnosed with HFMD by a throat swab were recruited for the analysis. Approximately half of the cohort was male (57.2%), 57.5% was aged < 2 years, and 57.5% lived in rural areas. The incidence rate was 279.72/100,000 person-years in Chiang Rai Province and 321.24 per 100,000 person-years in Pha Yao Province. Additionally, 42.5% of children were positive for human enterovirus; among these children, 56.1% were positive for enterovirus-A (EV-A), 17.7% were positive for coxsackievirus (CV), and 26.2% were positive for other human RNA enteroviruses. During the study period, 21 distinct outbreaks of HFMD were recognized. Four to five patients (total 92 patients) were selected from each outbreak for identifying its serotype; enterovirus-A71 (EV-A71) was detected in 34.8% of HFMD cases, coxsackievirus-A16 (CV-A16) in 26.1%, coxsackivirus-A6 (CV-A6) in 15.2%, coxsackievirus-A10 (CV-A10) in 10.9%, coxsackievirus-A4 (CV-A4) in 2.2%, coxsackievirus-B2 (CV-B2) in 2.2%, human rhinovirus in 2.2%, and unknown serotype in 6.4%. Multivariable analysis demonstrated that a history of breastfeeding for ≤6 months was associated with a higher chance of enterovirus infection than a history of breastfeeding > 6 months, and children who had mother who worked as farmers, daily wage employees, and unprofessional skilled jobs had a greater chance of enterovirus infection than those who had unemployed mothers. Coxsackievirus-infected children had a higher rate of rashes on the buttocks, knee, and elbow and fever but a lower rate of lethargy and malaise than EV-A71-infected children. CONCLUSIONS: EV-A71 is a major cause of HFMD in children < 6 years old in northern Thailand, but rash, fever, and mouth ulcers are mostly found in participants with coxsackievirus infection. Breastfeeding should be promoted during early childhood for at least 6 months to prevent HFMD particularly those mother who are working in unprofessional skill jobs.

Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence of hyperactivation of NFkappaB, AP1 and Nrf2 transcription factors. In addition to effluxing chemotherapeutic drugs, P-gp also plays a specific role in blocking caspase-dependent apoptotic pathways. One feature that cytotoxic treatments of cancer have in common is activation of the transcription factor NFkappaB, which regulates inflammation, cell survival and P-gp expression and suppresses the apoptotic potential of chemotherapeutic agents. As such, NFkappaB inhibitors may promote apoptosis in cancer cells and could be used to overcome resistance to chemotherapeutic agents. RESULTS: Although the natural withanolide withaferin A and polyphenol quercetin, show comparable inhibition of NFkappaB target genes (involved in inflammation, angiogenesis, cell cycle, metastasis, anti-apoptosis and multidrug resistance) in doxorubicin-sensitive K562 and -resistant K562/Adr cells, only withaferin A can overcome attenuated caspase activation and apoptosis in K562/Adr cells, whereas quercetin-dependent caspase activation and apoptosis is delayed only. Interestingly, although withaferin A and quercetin treatments both decrease intracellular protein levels of Bcl2, Bim and P-Bad, only withaferin A decreases protein levels of cytoskeletal tubulin, concomitantly with potent PARP cleavage, caspase 3 activation and apoptosis, at least in part via a direct thiol oxidation mechanism. CONCLUSIONS: This demonstrates that different classes of natural NFkappaB inhibitors can show different chemosensitizing effects in P-gp overexpressing cancer cells with impaired caspase activation and attenuated apoptosis.