Quercetin and 5-Fu Loaded Chitosan Nanoparticles Trigger Cell-Cycle Arrest and Induce Apoptosis in HCT116 Cells via Modulation of the p53/p21 Axis.

Nanoparticles (NPs) are encapsulating agents that exist in the nanometer range. They can be classified into different classes based on their properties, shapes, or sizes. Metal NPs, fullerenes, polymeric NPs, ceramic NPs, and luminescent nanoporous hybrid materials are only a few examples. This study explored the anticancer potential of quercetin and 5-fluorouracil-encapsulated chitosan nanoparticles (CS-5-FU-QCT NPs). The nanoparticles were prepared by ionic gelation, and their efficacy and mechanism of action were examined. CS-5-FU-QCT NPs were characterized using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR); cytotoxicity was analyzed using an MTT assay. Cells were treated with CS-5-FU-QCT NPs and incubated for 12, 24, and 36 h, and apoptosis analysis (using Annexin V/FITC), cell-cycle analysis, Western blotting, and confocal microscopic analysis were performed. Biophysical analysis revealed that the CS-5-FU-QCT NPs fall in the range of 300-400 nm with a near-spherical shape. The in vitro drug release profile indicates sustained release of drugs over a period of about 36 h. The cytotoxicity of CS-5-FU-QCT NPs was more prominent in HCT116 cells than in other cancer cells. This particular nanoformulation caused G0/G1 phase cell-cycle arrest in HCT116 cells and induced intracellular ROS generation, thereby causing apoptosis. It also downregulated Bcl2, cyclin D1, and Cdk4 and upregulated BAX, p53, and p21, causing cell-cycle arrest and apoptosis. In summary, CS-5-FU-QCT NPs hindered proliferation of HCT116 cells via ROS generation and altered the expression of key proteins in the p53/p21 axis and apoptotic machinery in a time-dependent manner.

The synergistic ramification of insoluble dietary fiber and associated non-extractable polyphenols on gut microbial population escorting alleviation of lifestyle diseases.

Most of the pertinent research which aims at exploring the therapeutic effects of polyphenols usually misapprehends a large fraction of non-extractable polyphenols due to their poor aqueous-organic solvent extractability. These polymeric polyphenols (i.e., proanthocyanins, hydrolysable tannins and phenolic acids) possess a unique property to adhere to the food matrix polysaccharides and protein sowing to their structural complexity with high glycosylation, degree of polymerization, and plenty of hydroxyl groups. Surprisingly resistance to intestinal absorption does not hinder its bioactivity but accelerates its functionality manifolds due to the colonic microbial catabolism in the gastrointestinal tract, thereby protecting the body from local and systemic inflammatory diseases. This review highlights not only the chemistry, digestion, colonic metabolism of non-extractable polyphenols (NEPP) but also summarises the synergistic effect of matrix-bound NEPP exerting local as well as systemic health benefits.

Kaempferol with Verapamil impeded panoramic chemoevasion pathways in breast cancer through ROS overproduction and disruption of lysosomal biogenesis.

BACKGROUND: Reactive oxygen species (ROS) at low level promotes cell survival through lysosome induced autophagy induction. Glucose stress induced acidosis, hypoxia, ROS, upregulates markers related to cancer stemness and multidrug resistance. Also, lysosomal upregulation is proposed to be one of the important indicators of cell survival under ROS induced stress. Studies supported that, stimulation of Lysosome-TFEB-Ca2+ cascade has important role in induction of chemoresistance and survival of cancerous cells. PURPOSE: To observe the effect of synergistic drug combination, Kaempferol and Verapamil on markers regulating chemoevasion, tumor stemness & acidosis as well as lysosome upregulation pathways, under low as well as high glucose conditions. HYPOTHESIS: Based on our earlier observation as well as previous reports, we hypothesized, our drug combination Kaempferol with Verapamil could attenuate markers related to chemoevasion, tumor stemness & acidosis as well as lysosome-TFEB-Ca2+ pathway, all of which have indispensable association and role in chemoresistance. METHODS: RNA and protein expression of candidate genes, along with ROS production and Ca2+ concentrations were measured in ex vivo models in altered glucose conditions upon treatment with KV. Also, computational approaches were utilized to hypothesize the mechanism of action of the drug combination. PCR, IHC, western blotting and molecular docking approaches were used in this study. RESULTS: The overproduction of ROS by our candidate drugs KV, downregulated the chemoresistance and tumor acidosis markers along with ATP1B1 and resulted in lysosomal disruption with reduction of Ca2+ release, diminishing TFEB expression under low glucose condition. An anomalous outcome was observed in high glucose conditions. We also observed KV promoted the overproduction of ROS levels thereby inducing autophagy-mediated cell death through the upregulation of LC3-II and p62 in low glucose conditions. The ex vivo studies also corroborate with in silico study that exhibited the parallel outcome. CONCLUSION: Our ex-vivo and in-silico studies revealed that our candidate drug combination KV, could effectively target several pathways regulating chemoresistance, that were not hitherto studied in the same experimental setup and thus may be endorsed for therapeutic purposes.

Effect of Bamboo Essential Oil on the Oxidative Stability, Microbial Attributes and Sensory Quality of Chicken Meatballs.

This study explores the efficacy of bamboo essential oil (BEO) incorporated at 15 ppm (T1, BEO-I) and 30 ppm (T2, BEO-II) on the overall physicochemical and oxidative stability, microbial deterioration, and sensory acceptability of meatballs stored for 20 days under refrigerated conditions. Analysis of various parameters, including physicochemical quality, color (CIE L*, CIE a* and CIE b*), generation of oxidative products (TBARS), microbial growth, and sensory acceptability of meatballs were evaluated at 5-day intervals. In addition, the total phenolics and flavonoid content of BEO were estimated, and fatty acids were determined by Gas chromatography (GC.) To gain insights into the biological activities of the BEO, antioxidant assays were determined in vitro using various methods. The antibacterial activity of BEO was also evaluated against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Vibrio cholera, Salmonella Typhimurium, Shigella flexneri, Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae) bacterial strains. The BEO contained a good quantity of total phenolics and flavonoids. In addition, the oil exhibited very potent antioxidant activity scavenging reactive oxygen and other such species, effectively showing IC50 at a very minimal concentration. Further, the BEO exhibited a strong antibacterial effect with MICs within 2 µL and MBCs from 5 to 7 µL for Gram-positive as well as Gram-negative bacteria, respectively. At both the concentrations used, BEO did not show any negative effect on the color of cooked meatballs but rather increased the microbiological and oxidative stability during the overall storage period. Meatballs treated with BEO had considerably reduced oxidative changes in terms of TBARS levels compared to the control. The total viable microbial count was lowest in BEO-treated meatballs and the highest in control. Both control and treated meatballs had a desirable flavor and good acceptability. The sensory attributes and aroma of treated meatballs were better and acceptable during the storage study, whereas the control samples were disliked by the panelists on 15th day. From this study, it can be concluded that bamboo essential oil could be used as a benign and non-toxic preservative to improve the quality and shelf life of cooked meatballs stored under refrigerated conditions.

Risk factors for coronary heart disease in Indians: a case-control study from Eastern India.

We conducted a hospital-based case-control investigation (150 cases and 176 controls) to examine the putative role of conventional risk factors in subjects with and without coronary heart disease from Eastern India. Multivariate binary logistic regression revealed the following as significant risk factors for coronary heart disease: male sex (OR = 4.6, p = 0.001), elevated total cholesterol/high-density lipoprotein ratio (OR = 4.0, p = 0.001), systolic blood pressure (OR = 3.0, p = 0.004), diastolic blood pressure (OR = 3.6, p = 0.002), fasting plasma glucose (OR = 3.0, p = 0.05), post-pondrial plasma glucose (OR = 3.2, p = 0.005), Impaired fasting glucose (OR = 3.7, p = 0.002), elevated triglyceride (OR = 3.1, p = 0.018), increased total cholesterol (OR = 3.0, p = 0.029), low-density lipoprotein (OR = 3.1, p = 0.001), low-density lipoprotein/high-density lipoprotein ratio (OR = 3.4, p = 0.004), central obesity (OR = 3.0, p = 0.006), smoking (OR = 3.7, p = 0.001) and urban residence (OR = 3.1, p = 0.003). In this study, the discriminant analysis showed that 77.2% of all entry for cases and 72.6% of all entry for controls were correctly classified using conventional risk factors and warrant early intervention for conventional risk factors.