Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of β-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3α/β was evaluated by western blot and IHC.
Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxol-resistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelial-mesenchymal transition (EMT) through repression of the p70S6K/GSK3/β-catenin signaling pathway.
Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/β-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.
METHODS: One million T2D people aged 40-79 registered in the National Diabetes Registry (2009-2018) were linked to death records (censored on 31 December 2019). Standardized absolute mortality rates and standardized mortality ratios (SMRs) were estimated relative to the Malaysian general population, and standardized to the 2019 registry population with respect to sex, age group, and disease duration.
RESULTS: Overall all-cause standardized mortality rates were unchanged in both sexes. Rates increased in males aged 40-49 (annual average percent change [AAPC]: 2.46 % [95 % CI 0.42 %, 4.55 %]) and 50-59 (AAPC: 1.91 % [95 % CI 0.73 %, 3.10 %]), and females aged 40-49 (AAPC: 3.39 % [95 % CI 1.32 %, 5.50 %]). In both sexes, rates increased among those with 1) > 15 years disease duration, 2) prior cardiovascular disease, and 3) Bumiputera (Malay/native) ethnicity. The overall SMR was 1.83 (95 % CI 1.80, 1.86) for males and 1.85 (95 % CI 1.82, 1.89) for females, being higher in younger age groups and showed an increasing trend in those with either > 15 years disease duration or prior cardiovascular disease.
CONCLUSIONS: Mortality trends worsened in certain T2D population in Malaysia.
METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).
RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.
CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.