Antiproliferative and Microtubule-stabilizing Activities of Two Iboga-vobasine Bisindoles Alkaloids from Tabernaemontana corymbosa in Colorectal Adenocarcinoma HT-29 Cells.

Two iboga-vobasine bisindoles, 16'-decarbomethoxyvoacamine (1: ) and its 19,20-dihydro derivative, 16'-decarbomethoxydihydrovoacamine (2: ) from Tabernaemontana corymbosa exhibited potent cytotoxicity against the human colorectal adenocarcinoma HT-29 cells in our previous studies. Bisindoles 1: and 2: selectively inhibited the growth of HT-29 cells without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with bisindoles 1: and 2: suppressed the formation of HT-29 colonies via G0/G1 cell cycle arrest and induction of mitochondrial apoptosis. Owing to its higher antiproliferative activity, bisindole 2: was chosen for the subsequent studies. Bisindole 2: inhibited the formation of HT-29 spheroids (tumor-like cell aggregates) in 3D experiments in a dose-dependent manner, while an in vitro tubulin polymerization assay and molecular docking analysis showed that bisindole 2: is a microtubule-stabilizing agent which is predicted to bind at the ß-tubulin subunit at the taxol-binding site. The binding resulted in the generation of ROS, which consequently activated the oxidative stress-related cell cycle arrest and apoptotic pathways, viz., JNK/p38, p21Cip1/Chk1, and p21Cip1/Rb/E2F, as shown by microarray profiling.

Functional role of circular RNAs in cancer development and progression.

Circular RNAs (circRNAs) are a large class of endogenously expressed non-coding RNAs formed by covalently closed loops through back-splicing. High throughput sequencing technologies have identified thousands of circRNAs with high sequence conservation and cell type specific expression in eukaryotes. CircRNAs play multiple important roles in cellular physiology functioning as miRNA sponges, transcriptional regulators, RBP binding molecules, templates for protein translation, and immune regulators. In a clinical context, circRNAs expression is correlated with patient's clinicopathological features in cancers including breast, liver, gastric, colorectal, and lung cancer. Additionally, distinct properties of circRNAs, such as high stability, exonuclease resistance, and existence in body fluids, show promising role for circRNAs as molecular biomarkers for tumor diagnosis, non-invasive monitoring, prognosis, and therapeutic intervention. Therefore, it is critical to further understand the molecular mechanism underlying circRNAs interaction in tumors and the recent progress of this RNA species in cancer development. In this review, we provide a detailed description of biological functions, molecular role of circRNAs in different cancers, and its potential role as biomarkers in a clinical context.

Rebaudioside A Enhances LDL Cholesterol Uptake in HepG2 Cells via Suppression of HMGCR Expression.

BACKGROUND: Rebaudioside A is one of the major diterpene glycosides found in Stevia had been reported to possess anti-hyperlipidemic effects. In this study, we explore the potential cholesterol-regulating mechanisms of Rebaudioside A in the human hepatoma (HepG2) cell line in comparison with simvastatin. METHODS: Cells were incubated with Rebaudioside A at several concentrations (0-10 µM) to determine the cytotoxicity by the MTT assay. Cells were treated with selected dosage (1 and 5 µM) in further experiments. Total cellular lipid was extracted by Bligh and Dyer method and subjected to quantitative colorimetric assay. To illustrate the effect of Rebaudioside A on cellular lipid droplets and low-density lipoprotein receptors, treated cells were subjected to immunofluorescence microscopy. Finally, we investigated the expression of experimental gene patterns of cells in response to treatment. RESULTS: In this study, cytotoxicity of Rebaudioside A was determined at 27.72 µM. Treatment of cells with a higher concentration of Rebaudioside A promotes better hepatocellular cholesterol internalization and ameliorates cholesterol-regulating genes such as HMGCR, LDLR, and ACAT2. CONCLUSION: In conclusion, our data demonstrated that Rebaudioside A is capable to regulate cholesterol levels in HepG2 cells. Hence, we proposed that Rebaudioside A offers a potential alternative to statins for atherosclerosis therapy.

Risk Factors and Prediction of Leptospiral Seropositivity Among Dogs and Dog Handlers in Malaysia.

This study determined the potential risk factors that may contribute to seropositivity among dogs and dog handlers from working dog and dog shelter institutions. Data was collected from dogs (n = 266) and dog handlers (n = 161) using a standardised guided questionnaire. Serum obtained from the dogs and dog handlers was tested using the microscopic agglutination test (MAT). A logistic regression analysis was used to predict leptospiral seropositivity of dogs and dog handlers based on potential risk factors. A total of 22.2% of dogs and 21.7% of dog handlers were seropositive. The significant predictors for the dogs' seropositivity were presence of rats (OR = 4.61 (95% CI: 1.05, 20.33), p = 0.043) and shared common area (OR = 5.12 (95% CI: 1.94, 13.46), p = 0.001) within the organisation. Significant predictor for dog handler seropositivity was contact time with the dogs of more than six hours/day (OR = 3.28 (95% CI: 1.28, 8.40), p = 0.013) after controlling for the effect of other risk factors such as small mammal contact, rat infestation at home, flooding at housing area (within three months) and urban locality. The exposure to various disease sources identified poses risk to dogs and dog handlers. Risk could be reduced with adequate application of protection at work while handling dogs and thus limiting contact with these sources and reducing exposure to infection.

Complete genome sequence of Planococcus donghaensis JH1T, a pectin-degrading bacterium.

The type strain Planococcus donghaensis JH1T is a psychrotolerant and halotolerant bacterium with starch-degrading ability. Here, we determine the carbon utilization profile of P. donghaensis JH1T and report the first complete genome of the strain. This study revealed the strain's ability to utilize pectin and d-galacturonic acid, and identified genes responsible for degradation of the polysaccharides. The genomic information provided may serve as a fundamental resource for full exploration of the biotechnological potential of P. donghaensis JH1T.