Geroprotective Effect of Levilactobacillus brevis and Weizmannia coagulans in Caenorhabditis elegans.

The prophylactic use of lactic acid bacteria (LAB) to maintain human health is one of the most important research areas in recent times. LAB supplementation confers a wide range of health benefits to the host, but few studies have focused on their possible role in delaying the aging process. This study explored the health and life-promoting properties of two LAB, Levilactobacillus brevis and Weizmannia coagulans, using the Caenorhabditis elegans model. We found that L. brevis and W. coagulans enhanced the intestinal integrity and intestinal barrier functions without affecting the overall physiological functions of C. elegans. Wild-type worms preconditioned with LAB strains increased their survival under oxidative and thermal stress conditions by reducing intracellular reactive oxygen levels. Live L. brevis and W. coagulans significantly extended the lifespan of C. elegans under standard laboratory conditions independently of dietary restrictions. Genetic and reporter gene expression analysis revealed that L. brevis and W. coagulans extend lifespan via insulin/insulin-like growth factor-1 signaling and the p38 MAPK signaling axis. Furthermore, sirtuin, JNK MAPK, and mitochondrial respiratory complexes were found to be partially involved in W. coagulans-mediated lifespan extension and stress resilience. Preconditioning with LAB ameliorated age-related functional decline in C. elegans and reduced ectopic fat deposition in an NHR-49-dependent manner. Together, our findings indicated that L. brevis and W. coagulans are worth exploring further as "gerobiotic" candidates to delay aging and improve the healthspan of the host.

Multifaceted Chiral Probe 2,3-Dihydro-4-hydroxy-chromene Schiff Base in Detecting Cu2+ Ions, l-Histidine, and Indazole: Spectroscopic Investigation and Confocal and Live Cell Imaging.

2,3-Dihydro-4-hydroxy-chromene-4(N)-ethyl thiosemicarbazone (probe F4) is used as a chemosensor, and it selectively detected Cu2+ ions among the metal ions by showing fluorescence "TURN ON" behavior. The stoichiometric binding of the probe with Cu2+ (CF4) was confirmed by Job's plot and mass spectroscopy. Further, CF4 was used as a sensor for the detection of l-amino acids and N-heterocyclic compounds. Among them, CF4 selectively detected l-histidine by showing fluorescence "TURN-OFF" behavior and selectively detected indazole by showing fluorescence "TURN-ON" behavior. These behaviors were further confirmed by in vivo live cell imaging studies by using Caenorhabditis elegans as a model. In vitro cytotoxicity was assayed for probe F4, complex CF4, and CF4 with l-histidine and indazole. The IC50 concentration was used for confocal imaging studies by using the MDA-MB-231 cell line (breast cancer cell line).

Visible light active hybrid silver decorated g-C3N4-CeO2 nanocomposite for ultrafast photocatalytic activity and toxicity evaluation.

Development of hybrid graphitic carbon nitride (GCN) nanocomposite is an emerging research area in wastewater treatment. Herein, hybrid visible light active photocatalyst of silver decorated polymeric graphitic carbon nitride and (Ag-GCN) with cerium oxide (CeO2) nanocomposite was prepared and characterized in detail. The Ag-GCN/CeO2 photocatalyst has successfully prepared by an electrostatic self-assembly approach. The synthesized Ag-GCN/CeO2 NCs photocatalysts are characterized by various physio-chemical techniques. Using the Ag-GCN/CeO2 catalyst, the excellent photodegradation efficiency of Acid yellow-36 (AY-36) and Direct yellow-12 (DY-12) dye solution were achieved 100% within 150 min sun light irradiation. The Ag-GCN/CeO2 rate constant values of 0.048 and 0.046/min has been determined for AY-36 and DR-12 dyes, respectively. The extraordinary photocatalytic activity is due to incorporation of CeO2 with Ag-GCN which play a significant role in visible light absorption, superior reactive oxygen generation (ROS) and excellent pollutant catalyst interaction. The toxicity of the photocatalytically degraded AY-36 and DR-12 dyes were measured using the soil nematode Caenorhabditis elegans, a well-established in vivo model in biology, by analyzing survival, physiological functions, intracellular ROS levels, and stress-protective gene expressions.

Green synthesis of zinc oxide nanoparticles using Cananga odorata essential oil and its antibacterial efficacy in vitro and in vivo.

Zinc oxide (ZnO) nanostructure exhibits antimicrobial properties, which have prompted more research on their bactericidal effect against foodborne pathogens. The present work focused on the green synthesis of ZnO nanoparticles (ZnO NPs) using Cananga odorata essential oil. The synthesized ZnO NPs were characterized by XRD, UV-Vis spectroscopy, zeta potential, SEM, and FT-IR analysis. The bactericidal activity of biosynthesized ZnO NPs was tested against Pseudomonas aeruginosa and Staphylococcus aureus. The in vitro results indicate that ZnO NPs have excellent antibacterial activity and that the bactericidal and bacteriostatic mechanisms are based on ROS production and depend on its penetration and interaction with bacterial cells. Moreover, ZnO NPs were found to be non-toxic to Caenorhabditis elegans, an in vivo animal model, up to 1 g/L and exert antibacterial activity by reducing the growth and colonization of pathogens. By reducing pathogen virulence, ZnO NPs significantly improved worms' physiological functions such as pharyngeal pumping, body length, reproduction, and movement. The competitive effect of ZnO NPs against pathogenic bacteria increased the gut-barrier integrity of C. elegans. The most interesting observation was noted that ZnO treatment increased the mean survival rate of P. aeruginosa and S. aureus infected C. elegans by 56.6 % and 62.4 %, respectively. As an outcome, our study proved that green synthesized ZnO NPs exhibit remarkable biological properties and can be used as an efficient bactericidal agent against foodborne pathogens.

Santalol Isomers Inhibit Transthyretin Amyloidogenesis and Associated Pathologies in Caenorhabditis elegans.

Transthyretin (TTR) is a homotetrameric protein found in human serum and is implicated in fatal inherited amyloidoses. Destabilization of native TTR confirmation resulting from mutation, environmental changes, and aging causes polymerization and amyloid fibril formation. Although several small molecules have been reported to stabilize the native state and inhibit TTR aggregation, prolonged use can cause serious side effects. Therefore, pharmacologically enhancing the degradation of TTR aggregates and kinetically stabilizing the native tetrameric structure with bioactive molecule(s) could be a viable therapeutic strategy to hinder the advancement of TTR amyloidoses. In this context, here we demonstrated α- and ß-santalol, natural sesquiterpenes from sandalwood, as a potent TTR aggregation inhibitor and native state stabilizer using combined in vitro, in silico, and in vivo experiments. We found that α- and ß-santalol synergize to reduce wild-type (WT) and Val30Met (V30M) mutant TTR aggregates in novel C. elegans strains expressing TTR fragments fused with a green fluorescent protein in body wall muscle cells. α- and ß-Santalol extend the lifespan and healthspan of C. elegans strains carrying TTRWT::EGFP and TTRV30M::EGFP transgene by activating the SKN-1/Nrf2, autophagy, and proteasome. Moreover, α- and ß-santalol directly interacted with TTR and reduced the flexibility of the thyroxine-binding cavity and homotetramer interface, which in turn increases stability and prevents the dissociation of the TTR tetramer. These data indicate that α- and ß-santalol are the strong natural therapeutic intervention against TTR-associated amyloid diseases.

α- and ß-Santalols Delay Aging in Caenorhabditis elegans via Preventing Oxidative Stress and Protein Aggregation.

α- and ß-Santalol (santalol isomers) are the most abundant sesquiterpenoids found in sandalwood, contributing to its pleasant fragrance and wide-spectrum bioactivity. This study aimed at identifying the antiaging and antiaggregation mechanism of α- and ß-santalol using the genetic tractability of an in vivo model Caenorhabditis elegans. The results showed that santalol isomers retard aging, improved health span, and inhibited the aggregation of toxic amyloid-ß (Aß1-42) and polyglutamine repeats (Q35, Q40, and HtnQ150) in C. elegans models for Alzheimer's and Huntington's disease, respectively. The genetic study, reporter gene expression, RNA-based reverse genetic approach (RNA interferences/RNAi), and gene expression analysis revealed that santalol isomers selectively regulate SKN-1/Nrf2 and EOR-1/PLZF transcription factors through the RTK/Ras/MAPK-dependent signaling axis that could trigger the expression of several antioxidants and protein aggregation inhibitory genes, viz., gst-4, gcs-1, gst-10, gsr-1, hsp-4, and skr-5, which extend longevity and help minimize age-induced protein oxidation and aggregation. We believe that these findings will further promote α- and ß-santalol to become next-generation prolongevity and antiaggregation molecules for longer and healthier life.

Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.

Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho+) and cholesterol-free (Cho-) medium with DG (5, 10 and 50µg/mL) at 20°C. It was observed that worms cultured in (Cho-) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (p<0.001) increased in transgenic worms exposed to DG with 50mM glucose, and storage of lipid in intestinal cells was reduced in N2 wild type worms. Genetic requirement of DG induced longevity was studied with different mutant strains of mev-1, daf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol.