Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone.

Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged as a potent anti-inflammatory and anti-angiogenic compound with substantial potential, as evidenced by previous studies. This study aimed to explore the potential of BQ in suppressing angiogenesis and metastasis in the human CRC cell lines LoVo and HCT116. Various in vitro and in silico studies have been conducted to elucidate the potential pathway(s) of BQ. BQ was highly cytotoxic, with an IC50 of 7.01 ± 0.6 µM in HCT116 and 9.58 ± 0.8 µM in LoVo cells. Moreover, BQ induced notable apoptotic activity and suppressed migration, invasion, and adhesion in both cell lines. The inhibition of MMP-2 suggests the potential of BQ to impede extracellular matrix degradation and CRC cell metastasis. BQ inhibits the expression of key proteins involved in angiogenesis and metastasis, including VEGF-A, VEGF-C, BRAF, ERK, KRAS, PI3K, and AKT. Molecular docking simulations illustrated the robust binding of BQ to CRC protein receptors. BQ holds promise in impeding CRC progression by targeting angiogenesis and metastasis, particularly through inhibition of the KRAS/BRAF/ERK and KRAS/PI3K/AKT signaling pathways.

Impact of vaccination on COVID-19 severity during the second wave in Brunei Darussalam, 2021.

Objective: Coronavirus disease (COVID-19) vaccinations have been shown to prevent infection with efficacies ranging from 50% to 95%. This study assesses the impact of vaccination on the clinical severity of COVID-19 during the second wave in Brunei Darussalam in 2021, which was due to the Delta variant. Methods: Patients included in this study were randomly selected from those who were admitted with COVID-19 to the National Isolation Centre between 7 August and 6 October 2021. Cases were categorized as asymptomatic, mild (symptomatic without pneumonia), moderate (pneumonia), severe (needing supplemental oxygen therapy) or critical (needing mechanical ventilation) but for statistical analysis purposes were dichotomized into asymptomatic/mild or moderate/severe/critical cases. Univariate and multivariable analyses were conducted to identify risk factors associated with moderate/severe/critical disease. Propensity score-matched analysis was also performed to evaluate the impact of vaccination on disease severity. Results: The study cohort of 788 cases (mean age: 42.1 ± 14.6 years; 400 males) comprised 471 (59.8%) asymptomatic/mild and 317 (40.2%) moderate/severe/critical cases. Multivariable logistic regression analysis showed older age group (≥ 45 years), diabetes mellitus, overweight/obesity and vaccination status to be associated with increased severity of disease. In propensity score-matched analysis, the relative risk of developing moderate/severe/critical COVID-19 for fully vaccinated (two doses) and partially vaccinated (one dose) cases was 0.33 (95% confidence interval [CI]: 0.16-0.69) and 0.62 (95% CI: 0.46-0.82), respectively, compared with a control group of non-vaccinated cases. The corresponding relative risk reduction (RRR) values were 66.5% and 38.4%, respectively. Vaccination was also protective against moderate/severe/critical disease in a subgroup of overweight/obese patients (RRR: 37.2%, P = 0.007). Discussion: Among those who contracted COVID-19, older age, having diabetes, being overweight/obese and being unvaccinated were significant risk factors for moderate/severe/critical disease. Vaccination, even partial, was protective against moderate/severe/critical disease.

Antidiabetic activities of alkaloids isolated from medicinal plants

Diabetes mellitus is a metabolic disorder affecting a great part of population around the world. It is the fifth leading death causing disease in the world and its cases are increasing day by day. Traditional medicine is thought to have promising future in the treatment of diabetes mellitus. In contrast to synthetic drugs phytochemicals are considered to be free from side effects. As one of the main class of natural products, alkaloids and their derivatives have been widely used as sources of pharmacological agents against a variety of medical problems. Many studies confirmed the role of alkaloids in the management of diabetes and numerous alkaloids isolated from different medicinal plants were found active against diabetes. Like other natural products, alkaloids regulate glucose metabolism either by inhibiting or inducing multiple candidate proteins including AMP-activated protein kinase, glucose transporters, glycogen synthase kinase-3, sterol regulatory element-binding proteins 1, glucokinase, glucose-6-phosphatase, acetyl-CoA carboxylase among the others. A comprehensive review of alkaloids reported in the literature with anti-diabetic activities and their target enzymes is conducted, with the aim to help in exploring the use of alkaloids as anti-diabetic agents. Future work should focus on rigorous clinical studies of the alkaloids, their development and relevant drug targets.