Our previous findings demonstrated that Helichrysetin possessed promising anti-cancer activity. It was able to induce apoptosis in the A549 cell line. However, its mechanism of action is unknown. The present study aimed to unravel possible underlying molecular mechanisms of helichrysetin-induced apoptosis in A549 (human lung carcinoma) cells using comparative quantitative proteomics (iTRAQ labeled), followed by an exhaustive bioinformatics analysis. Our results suggested that DNA damage response (DDR) and cell cycle arrest were responsible for lung cancer cell death with helichrysetin treatment. Among proteins that changed in abundance were Nrf2 and HMOX1. They are oxidative stress-related proteins and were increased in abundance. BRAT1 was also increased in abundance, suggesting an increase in DNA damage repair, indicating the occurrence of DNA damage due to oxidative stress. However, several essential DDR downstream proteins such as p-ATM, BRCA1, FANCD2, and Rb1 that would further increase DNA damage were found to be dramatically decreased in relative abundance. Cell cycle-related proteins, p53, p21, and cyclin D1, were increased while cyclin A, cyclin E, and cdk2 were decreased. This is predicted to facilitate S-phase arrest. Furthermore, excessive DNA damage and prolonged arrest would in turn result in the induction of mitochondrial-mediated apoptosis. Based on these observations, we postulate that the effects of helichrysetin were in part via the suppression of DNA damage response which led to DNA damage and prolonged cell cycle arrest. Subsequently, this event initiated mitochondrial-mediated apoptosis in A549 lung cancer cells.
Crossbreeding of zebu cattle (Bos indicus) with European breeds (Bos taurus) producing crossbred cattle was performed to overcome the low growth rates and milk production of indigenous tropical cattle breeds. However, zebu cattle fertility is higher than those of crossbred cattle and European breeds under warm conditions. Combination study of proteomics and metabolomics toward Malaysian indigenous breed Kedah × Kelantan-KK (B. indicus) and crossbreed Mafriwal-M (B. taurus × B. indicus) to understand physiological reasons for higher thermotolerance and fertility in Zebu cattle sperm. 161 regulated metabolites and 96 regulated proteins in KK and M (p < 0.05) showed more efficient carbohydrate and energy metabolism, higher integrity of the DNA and plasma membrane, a lower level of reactive oxygen species, and higher levels of phospholipids, which confirmed higher sperm plasma membrane integrity in KK. A stronger antioxidant system and lower polyunsaturated fatty acids help KK sperm cope with oxidative stress under warm conditions. The higher abundance of flagella structural proteins in KK provides a stronger structure that supports sperm motility. Abnormality of flagella, plasma membrane disruption, and DNA fragmentation were higher in M. These findings provide selective molecular markers for developing high-producing and more thermotolerant cattle breeds in tropical areas (197 words).
Recently, there has been a high demand for the development of yogurt-based nutraceuticals and functional medications. This surge is primarily driven by the increasing global need for pharmaceutical and nutraceutical products, arising from widespread nutrient deficiencies and the emergence of various communicable and non-communicable diseases (NCDs), including respiratory infections, cancer, gastrointestinal, diabetes, obesity, and cardiovascular diseases. Probiotic yogurt provides an effective medium for delivering essential nutrients to the human body. Additionally, various prebiotic combinations, such as bioactive compounds from plants, animals, and microbes, can enrich the viability of probiotics, nutritional value, and efficacy. However, the gastric environment can significantly impact the viability of probiotic microorganisms as well as the absorption of nutrients and bioactive molecules. Therefore, utilizing biopolymer-based encapsulation for functional nutrients, metal nanostructures, and medications can improve the bioavailability of these compounds, protect the probiotics from gastric enzymes, increase nutrient and microbial absorption in colonic fluids, and enhance the antioxidant level in the body. This review investigates various methods for producing yogurt enriched with prebiotic and probiotic combinations alongside techniques such as microencapsulation, emulsification, and the incorporation of metal nanoparticles. Key factors such as viability, texture, and syneresis are examined to optimize yogurt-based nutraceuticals and functional medications.