Q-TOF LC-MS compounds evaluation of propolis extract derived from Malaysian stingless bees, Tetrigona apicalis, and their bioactivities in breast cancer cell, MCF7.

Propolis is known to exhibit various phytochemical compounds that aid in several biological activities. The current study investigates the phytochemical compounds of ethanolic extract of propolis of Tetrigona apicalis (EEP) using Q-TOF LC-MS, its antioxidant properties using DPPH and ABTS+ radical scavenging assays, total phenolic (TPC) and flavonoid content (TFC), using Folin-Ciocalteu and Aluminium Chloride method, respectively, as well as proapoptotic effects, based on the selected IC50 of the cytotoxic study conducted for EEP using annexin V-FITC assay. Terpene and polyphenol were among of 17 identified compounds. The EC50 of EEP for DPPH and ABTS+ was 1.78 mg/mL and 1.68 mg/mL, while the EEP exhibited TPC and TFC values of 31.99 mgGAE/g and 66.4 mgQCE/g, respectively in which the parameters were strongly correlated. The IC50 of EEP effectively induces apoptosis in MCF7 cells. In conclusion, EEP possessed important phytochemical compounds that work excellently as antioxidants and anticancer agents.

Biocompatible magnesium-doped biphasic calcium phosphate for bone regeneration.

Autologous bone grafting remains the gold standard for almost all bone void-filling orthopedic surgery. However, autologous bone grafting has several limitations, thus scientists are trying to identify an ideal synthetic material as an alternative bone graft substitute. Magnesium-doped biphasic calcium phosphate (Mg-BCP) has recently been in the spotlight and is considered to be a potential bone substitute. The Mg-BCP is a mixture of two bioceramics, that is, hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP), doped with Mg2+ , and can be synthesized through chemical wet-precipitation, sol-gel, single diffusion gel, and solid state reactions. Regardless of the synthesis routes, it is found that the Mg2+ preferentially accommodates in ß-TCP lattice instead of the HA lattice. The addition of Mg2+ to BCP leads to desirable physicochemical properties and is found to enhance the apatite-forming ability as compared to pristine BCP. In vitro results suggest that the Mg-BCP is bioactive and not toxic to cells. Implantation of Mg-BCP in in vivo models further affirmed its biocompatibility and efficacy as a bone substitute. However, like the other bioceramics, the optimum physicochemical properties of the Mg-BCP scaffold have yet to be determined. Further investigations are required regarding Mg-BCP applications in bone tissue engineering.

Risk factors for mortality among COVID-19 patients.

AIMS: COVID-19 is a current global pandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells.

AIMS: Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells. MAIN METHODS: Quantitative RT-PCR and Western blot analysis were used to assess the mRNA and protein expression of the three CYPs. CYP3A4 enzyme activity was evaluated using P450-Glo™ Assays. The LanthaScreen® TR-FRET PXR (SXR) Competitive Binding Assay was used to determine if the compounds are potential PXR-ligands. KEY FINDINGS: Both diterpenoids inhibited the mRNA and protein expressions of CYP1A2, CYP2D6, and CYP3A4. Interestingly, the lowest concentration of both diterpenoids produced a more than 50% reduction in the mRNA and protein expression of CYP3A4 and this reduction was consistent with the enzyme activity. Further experiments revealed that both diterpenoids were also capable of attenuating the ability of dexamethasone to induce CYP3A4 expression, and 14-Deoxy-11, 12-Didehydroandrographolide tended to bind to the PXR-LBD site in a concentration-dependent manner. SIGNIFICANCE: These diterpenoids are potential CYP3A4 inhibitors and the effects on CYP3A4 may be clinically significant. 14-Deoxy-11, 12-Didehydroandrographolide inhibits CYP3A4 by binding and antagonizing PXR function.

Programmed cell death pathways and current antitumor targets.

Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.