Novel tetrahydroquinoline derivatives induce ROS-mediated apoptosis in glioblastoma cells.

Current treatment for Glioblastoma Multiforme (GBM) is not efficient due to its aggressive nature, tendency to infiltrate surrounding brain tissue, and chemotherapy resistance. Tetrahydroquinoline scaffolds are emerging as a new class of drug for treating many human cancers including GBM. This study investigates the cytotoxicity effect of eight novel derivatives of 2-((3,4-dihydroquinolin-1(2H)-yl)(aryl)methyl)phenol, containing substitute 1 with reduced dihydroquinoline fused with cyclohexene ring and substitute 2 with phenyl and methyl group. The 4-position of the aryl ring was determinant for the desired cytotoxicity, and out of the 8 synthesized compounds, the 4-trifluoromethyl substituted derivative (4ag) exhibited the most anti-GBM potential effect compared to the standard chemotherapeutic agent, temozolomide (TMZ), with IC50 values of 38.3 µM and 40.6 µM in SNB19 and LN229 cell lines, respectively. Our results demonstrated that 4ag triggers apoptosis through the activation of Caspase-3/7. In addition, 4ag induced intracellular reactive oxygen species (iROS) which in turn elevated mitochondrial ROS (mtROS) and causes the disruption of the mitochondrial membrane potential (Δψmt) in both GBM cells. This compound also exhibited anti-migratory properties over the time in both the cell lines. Overall, these findings suggest that tetrahydroquinoline derivative, 4ag could lead to the development of a new drug for treating GBM.

Potential of fermented foods and their metabolites in improving gut microbiota function and lowering gastrointestinal inflammation.

Foods prepared using microbial conversion of major and minor food components, which are otherwise known as fermented foods continue to impact human health. The live microorganisms and transformed metabolites can also have a deep influence on the gut microbiota, the multifaceted population of microorganisms dwelling inside the gut play a key role in wellbeing of an individual. The probiotic strains delivered through the consumption of fermented food and other bioactive components such as polyphenolic metabolites, bioactive peptides, short-chain fatty acids and others including those produced via gut microbiota mediated transformations have been proposed to balance the gut microbiota diversity and activity, and also to regulate the inflammation in the gut. However, little is known about such effects and only a handful of fermented foods have been explored to date. We herein review the recent knowledge on the dysbiotic gut microbiota linking to major gut inflammatory diseases. Also, evidences that fermented food consumption modulates the gut microbiota, and its impact on the gut inflammation and inflammatory diseases have been discussed. © 2024 Society of Chemical Industry.

Lactic acid bacteria in the functional food industry: biotechnological properties and potential applications.

With the growing demand for functional foods having better nutraceutical properties, lactic acid bacteria (LAB) has become an important industrial microorganism. LAB play a significant role in the functional food industry by exhibiting probiotic properties and has the ability to produce various biologically active metabolites such as γ-aminobutyric acid (GABA), exopolysaccharides (EPSs), conjugated linoleic acid (CLA), bacteriocins, reuterin and reutericyclin, which provides enhanced nutraceutical properties to the final food products. LAB are also known to produce several specific enzymes essential for producing substrate-derived bioactive compounds, such as polyphenols, bioactive peptides, inulin-type fructans and ß-glucans, fatty acids, and polyols. These compounds exhibit many health benefits, including better mineral absorption, oxidative stress protection, blood glucose and cholesterol-lowering properties, prevention of gastrointestinal tract infections and improved cardiovascular function. Further, metabolically engineered LAB have been widely used for the nutritive enhancement of different food products and the application of CRISPR-Cas9 holds tremendous potential for the engineering of food cultures. This review provides an overview of the use of LAB as probiotics, its application in producing fermented foods and nutraceutical products, and its health benefits on the host.

Effects of nonsurgical periodontal therapy on serum creatinine level in systemically healthy individuals with periodontitis: An interventional study.

Background: Several studies have suggested a relationship between periodontitis and serum creatinine levels. Both low and high serum creatinine levels have been reported in individuals with periodontitis. The impact of periodontal therapy on serum creatinine levels has not been fully investigated yet. The aim of the study is to estimate the influence of nonsurgical periodontal therapy (NSPT) on serum creatinine levels in systemically healthy individuals with periodontitis at stage II and stage III with grade A and grade B. Materials and Methods: Sixty-eight systemically healthy individuals included in the study were divided into Group A (GA) (Periodontally healthy) and Group B (GB) (Periodontitis: stage II and III with grade A and grade B). Gingival index, sulcular bleeding index, probing pocket depth, clinical attachment level, body mass index, and serum creatinine levels were recorded at baseline for both GA and GB, 90 days after NSPT for GB only. Collected data were analyzed statistically. Results: Serum creatinine levels in GB were significantly higher when compared with GA and serum creatinine levels in GB before and 90 days after NSPT were statistically insignificant. Conclusions: Serum creatinine levels were higher in individuals with periodontitis when compared with periodontally healthy individuals and NSPT has no considerable influence on the serum creatinine levels in individuals with periodontitis. Further studies are required to confirm these findings.

Iatrogenic cold urticaria induced by tetrafluoroethane cryosurgery for gingival depigmentation: A rare case report.

INTRODUCTION: Gingival depigmentation procedure has gained widespread popularity in the recent years due to increased esthetic demands among patients. Among the various depigmentation procedures, cryosurgery is inexpensive and straightforward method. This case report discusses a rare complication associated with tetrafluoroethane (TFE) cryosurgical depigmentation method. CASE PRESENTATION: A 27-year-old systemically healthy male patient reported with the complaint of esthetic concerns associated with gingival melanin pigmentation. Cryosurgery with TFE was planned for the maxillary first quadrant. The patient developed angioedema immediately after exposure to the TFE cryogen during the procedure. Cold urticaria was considered, and the patient was prescribed nonsedating antihistamines for a week. One month follow-up showed completely healed and depigmented gingiva without any recession or attachment loss. CONCLUSIONS: TFE cryosurgery depigmentation was found to be an effective depigmentation procedure. However, various complications including cold urticaria have been associated with its application. Therefore, the procedure's success depends on the proper case selection, complete isolation of the operating area, and preoperative test for gingival tissue response. KEY POINTS: Why is this case new information? Cold urticaria formation after applying cryosurgery has never been reported in the literature to the best of the authors' knowledge. What are the keys to the successful management of this case? Preoperative testing for tissue response to cryosurgery will prevent complications like cold urticaria. What are the primary limitations to success in this case? Improper medical history and not taking tissue response test for cryosurgery.

Matrix metalloproteinase-9-1562 C/T promoter gene polymorphism in chronic periodontitis: A cross-sectional observational study.

Background: Matrix metalloproteinases (MMPs) are a major group of enzymes, released in inflamed periodontal tissues in large quantities, resulting in connective tissue matrix breakdown. One of the most predominant MMPs is MMP-9. Association between chronic periodontitis (CP) and MMP-9 gene polymorphism (GP) in some ethnic populations has been already established. The aim of the current study was to assess the association of single-nucleotide polymorphism in the promoter region of MMP-9 gene with CP in Kolkata population, if any. Materials and Methods: Forty eligible individuals were recruited for the study and grouped as A and B: Group A (twenty periodontally healthy individuals) and Group B (twenty CP patients). Venous blood samples collected from all the forty individuals were used to isolate the genomic DNA. GP for MMP-9 gene was detected using polymerase chain reaction and sequencing method. The data obtained were then analyzed statistically. Results: A significantly different genotypic and allelic variation was observed in the control and test groups, with C/T genotype and T allele present in only CP group. Conclusion: Within the limitations of this study, we can conclude that there was no significant association between patients with periodontitis and MMP-9-1562 C/T promoter GP.

Expression of matrix metalloproteinase-9 in gingival tissue biopsy in patients with slowly/ moderately and rapidly progressing periodontitis: An observational study.

BACKGROUND: Matrix metalloproteinases (MMPs) are a group of host-derived zinc-dependent enzymes which mediates the destruction of the extracellular matrix. In periodontitis, there is excess production of MMPs associated with periodontal tissue destruction. The aim of this study was to estimate the level MMP-9 in both active and latent form in gingival tissue (GT) samples collected from periodontitis patients with different rates of progression and compare it with healthy individuals. MATERIALS AND METHODS: Sixty patients were selected and divided into three groups, 20 each: Group A (slowly/moderately progressing periodontitis), Group B (rapidly progressing periodontitis), and Group C (clinical periodontal health). Plaque index, gingival index, periodontal probing depth (PPD), and clinical attachment level were recorded. GT samples were collected from all 60 patients and MMP-9 expressions were measured using gelatin zymography and western blotting. RESULTS: Levels of active MMP-9 (aMMP-9) and latent MMP-9 (lMMP-9) were significantly high in both Group A (GA) (aMMP-9: 2.05 arbitrary unit [AU]/lMMP-9: 2.54 AU) and Group B (GB) (aMMP-9: 1.32 AU/lMMP-9: 1.74 AU) when compared to that of Group C (GC) (aMMP-9: 0.93/lMMP-9: 1.08 AU). In GA, levels of aMMP-9 showed a significant correlation with PPD values. No other correlations were found. CONCLUSION: The levels of aMMP-9 and lMMP-9 were increased in both the types of periodontitis when compared with periodontally healthy individuals. A significant correlation was found between PPD and activities of aMMP-9 in slowly/moderately progressing periodontitis patients. However, further studies are required to confirm these findings.

Production, characterization and molecular docking of antioxidant peptides from peptidome of kinema fermented with proteolytic Bacillus spp.

Kinema is an alkaline traditionally fermented soybean product popularly consumed in Sikkim Himalayan region. Kinema was prepared by soybean fermented with different species of Bacillus and analyzed for peptide content, antioxidant activity and consequence of gastrointestinal enzymes (pepsin and pancreatin) on the antioxidant effect. Antioxidant effect was enhanced during soybean fermentation using different starters, which further increased during gastrointestinal digestion. The peptides formed during soybean fermentation were analyzed using LC-MS/MS. Soybean fermented using different starters resulted in the production of some common peptides and a large number of unique peptides, which may affect the functional property of kinema. Peptides having antioxidative amino acids (histidine, phenylalanine, methionine, tryptophan and tyrosine) and significant GRAVY value were selected for their molecular interaction with myeloperoxidase (MPO), a key enzyme responsible for elevated oxidative stress. A peptide SEDDVFVIPAAYPF produced in kinema fermented using Bacillus licheniformis 1G had interaction with four out of five catalytic residues identified in MPO. Kinema prepared using specific starter can produce unique peptides responsible for specific health benefits.

Calcium sensing receptor modulation for cancer therapy.

The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.