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Peng HH et al. (2021) Aging (Albany NY) "Ganoderma lucidum stimulates autophagy-dependent longevity pathways in Caenorhabditis elegans and human cells."

Hsiao YC, Liau JC, Martel J, Ke PY, Chiu CY, Ojcius DM, Su YH, Ko YF, Peng HH, Chang IT, Young JD, Wu CY

[

Aging (Albany NY),

2021]

The medicinal fungus Ganoderma lucidum is used as a dietary supplement and health tonic, but whether it affects longevity remains unclear. We show here that a water extract of G. lucidum mycelium extends lifespan of the nematode Caenorhabditis elegans. The G. lucidum extract reduces the level of fibrillarin (FIB-1), a nucleolar protein that correlates inversely with longevity in various organisms. Furthermore, G. lucidum treatment increases expression of the autophagosomal protein marker LGG-1, and lifespan extension is abrogated in mutant C. elegans strains that lack atg-18, daf-16, or sir-2.1, indicating that autophagy and stress resistance pathways are required to extend lifespan. In cultured human cells, G. lucidum increases concentrations of the LGG-1 ortholog LC3 and reduces levels of phosphorylated mTOR, a known inhibitor of autophagy. Notably, low molecular weight compounds (<10 kDa) isolated from the G. lucidum water extract prolong lifespan of C. elegans and the same compounds induce autophagy in human cells. These results suggest that G. lucidum can increase longevity by inducing autophagy and stress resistance.

Jose A et al. (2024) MicroPubl Biol "NALCN Channels Are Not Major targets of Gα _o or Gα _q Modulation in the C. elegans Egg-Laying Behavior Circuit."

Jose A, Collins K

[

MicroPubl Biol,

2024]

Sodium leak channels (NALCN) are regulators of cell membrane potential. Previous studies in mammalian neurons and C. elegans have shown that Gα q and Gα o signaling antagonistically modulates NALCN activity to regulate neuron excitability and neurotransmitter release for behavior. Here, we test whether NALCNs mediate the effects of Gα q and/or Gα o signaling in the C. elegans egg-laying circuit. We find that while gain-of-function NALCN mutants exhibit hyperactive egg-laying behavior, NALCNs are not required for the effects of Gα q or Gα o signaling for egg laying. These results show that NALCNs are not major effectors of G-protein signaling for C. elegans egg-laying behavior.

Pandey G et al. (2019) ACS Biomater Sci Eng "Chitosanylated MoO₃-Ruthenium(II) Nanocomposite as Biocompatible Probe for Bioimaging and Herbaceutical Detection."

Ravichandiran V, Pandey G, Kanagavalli P, Balamurugan K, Veerapandian M, Marimuthu M

[

ACS Biomater Sci Eng,

2019]

Hybrid nanomaterials with inherent physicochemical properties and cytocompatibility are beneficial for healthcare utilities. This paper demonstrates the hybridization of transition-metal oxide (molybdenum trioxide, MoO3), optoelectrochemically active dye complex (Ru(II)), and biopolymer (chitosan, CS) into a single nanosystem. The asafetida-resin-mediated green synthesis of MoO3 nanoparticles (g-MoO3 NPs) enabled chemical adsorption of Ru(II) and CS. Optical imaging functionality of pristine g-MoO3, g-MoO3-Ru(II), and g-MoO3-Ru(II)/CS has been evaluated using Caenorhabditis elegans, as an in vivo animal model, at an excitation wavelength of 450 nm and observed emission of 600 nm. The localization of chitosan on the surface of g-MoO3-Ru(II) exhibits cytocompatibility promising for intracellular imaging. The intracellular antioxidant properties of the g-MoO3-Ru(II)/CS nanocomposite are more profound than pristine NPs as assessed by measuring reactive oxygen species and protein carbonyls against the standard drug resveratrol. The electrochemical transducing ability of the hybrid g-MoO3-Ru(II) nanocomposite has been tested using butein, as a model herbaceutical, with nanomolar precision (50-1250 nM). The triad composite of metal oxide, dye, and biopolymer enabled synergistic properties that are suitable for multifunctional application in intracellular imaging, antioxidant, and electrochemical sensor studies.

Anderson A et al. (2019) Infect Immun "Identification of a conserved, orphan G-protein coupled receptor required for efficient pathogen clearance in C. elegans."

Schafer W, McMullan R, Anderson A, Chew YL

[

Infect Immun,

2019]

G-protein coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. Whilst it has become well established that the nematode worm Caenorhabditis elegans triggers innate immune responses following infection with numerous bacterial, fungal and viral pathogens, the mechanisms by which C. elegans recognises these pathogens have remained somewhat more elusive. C. elegans G-protein coupled receptors have been implicated in recognising pathogen-associated damage and activating downstream host immune responses. Here we identify and characterise a novel G-protein coupled receptor required to regulate the C. elegans response to infection with Microbacterium nematophilum We show that this receptor, which we designate PCDR-1, is required for efficient pathogen clearance following infection. PCDR-1 acts upstream of multiple G-proteins including the C. elegans Gq ortholog EGL-30 in rectal epithelial cells to promote pathogen clearance via a novel mechanism.

Liu Z et al. (2024) Toxics "Transgenerational Response of Germline Nuclear Hormone Receptor Genes to Nanoplastics at Predicted Environmental Doses in Caenorhabditis elegans."

Bian Q, Wang Y, Liu Z, Wang D

[

Toxics,

2024]

Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.

Okoro NO et al. (2023) Food Funct "Ganoderma lucidum methyl ganoderate E extends lifespan and modulates aging-related indicators in Caenorhabditis elegans."

Okoro NO, Liu Y, Wang B, Odiba AS, Jin C, Fang W, Omeje EO, Liu H, Osadebe PO, Liao G, Han J

[

Food Funct,

2023]

Methyl Ganoderate E (MGE) is a triterpenoid derived from Ganoderma lucidum (Reishi), an edible mushroom, commonly processed into food forms such as soups, drinks, culinary dishes, and supplements. MGE has been shown to inhibit 3T3-L1 murine adipocyte differentiation when combined with other G. lucidum triterpenes. However, the specific effect of MGE on biological processes remains unknown. In this study, we present the first evidence of MGE's anti-aging effect in Caenorhabditis elegans. Through our screening process using the UPRER regulation ability, we evaluated a library of 74 pure compounds isolated from G. lucidum, and MGE exhibited the most promising results. Subsequent experiments demonstrated that MGE extended the lifespan by 26% at 10 μg ml-1 through daf-16, hsf-1, and skn-1-dependent pathways. MGE also enhanced resistance to various molecular stressors, improved healthspan, increased fertility, and reduced the aggregation of alpha-synuclein and amyloid-beta. Transcriptome data revealed that MGE promoted processes associated with proteolysis and neural activity, while not promoting cell death processes. Collectively, our findings suggest that G. lucidum MGE could be considered as a potential anti-aging intervention, adding to the growing list of such interventions.

Andrade G et al. (2020) J Fungi (Basel) "Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity."

Scorzoni L, Bastos JK, Carvalho MTM, Mendes-Giannini MJS, Pires RH, Martins CHG, Orlando HCS, Veneziani RCS, Ambrosio SR, Andrade G, Abrao F, Pedroso RS

[

J Fungi (Basel),

2020]

Plants belonging to the genus Copaifera are widely used in Brazil due to their antimicrobial properties, among others. The re-emergence of classic fungal diseases as a consequence of antifungal resistance to available drugs has stimulated the search for plant-based compounds with antifungal activity, especially against Candida. The Candida-infected Caenorhabditis elegans model was used to evaluate the in vitro antifungal potential of Copaifera leaf extracts and trunk oleoresins against Candida species. The Copaifera leaf extracts exhibited good antifungal activity against all Candida species, with MIC values ranging from 5.86 to 93.75 g/mL. Both the Copaifera paupera and Copaifera reticulata leaf extracts at 46.87 g/mL inhibited Candida glabrata biofilm formation and showed no toxicity to C. elegans. The survival of C. glabrata-infected nematodes increased at all the tested extract concentrations. Exposure to Copaifera leaf extracts markedly increased C. glabrata cell vacuolization and cell membrane damage. Therefore, Copaifera leaf extracts are potential candidates for the development of new and safe antifungal agents.

Lockyer JL et al. (2024) Proc Natl Acad Sci U S A "Selective optogenetic inhibition of Gα_q or Gα_i signaling by minimal RGS domains disrupts circuit functionality and circuit formation."

Lin JY, McMullen JPD, Newland JW, Reading A, Foa L, Marshall OJ, Delandre C, Gasperini R, Viswanathan S, Vicenzi S, Zbela A, Lockyer JL

[

Proc Natl Acad Sci U S A,

2024]

Optogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate an optogenetic tool that disrupts Gαq signaling through membrane recruitment of a minimal regulator of G protein signaling (RGS) domain. This approach, Photo-induced Gα Modulator-Inhibition of Gαq (PiGM-Iq), exhibited potent and selective inhibition of Gαq signaling. Using PiGM-Iq we alter the behavior of Caenorhabditis elegans and Drosophila with outcomes consistent with GPCR-Gαq disruption. PiGM-Iq changes axon guidance in cultured dorsal root ganglia neurons in response to serotonin. PiGM-Iq activation leads to developmental deficits in zebrafish embryos and larvae resulting in altered neuronal wiring and behavior. Furthermore, by altering the minimal RGS domain, we show that this approach is amenable to Gαi signaling. Our unique and robust optogenetic Gα inhibiting approaches complement existing neurobiological tools and can be used to investigate the functional effects neuromodulators that signal through GPCR and trimeric G proteins.

Niu L et al. (2020) Proc Natl Acad Sci U S A "Melatonin promotes sleep by activating the BK channel in C. elegans."

Liu P, Shui Y, Wang ZW, Li Y, Chen B, Zong P, Niu L

[

Proc Natl Acad Sci U S A,

2020]

Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these effects are nonadditive in double knockouts. Exogenous Mel inhibits neurotransmitter release and promotes sleep in wild-type (WT) but not pcdr-1 and slo-1 mutants. In a heterologous expression system, Mel activates the human BK channel (hSlo1) in a membrane-delimited manner in the presence of the Mel receptor MT1 but not MT2 A peptide acting to release free G also activates hSlo1 in a MT1-dependent and membrane-delimited manner, whereas a G inhibitor abolishes the stimulating effect of Mel. Our results suggest that Mel promotes sleep by activating the BK channel through a specific Mel receptor and G.

Sathiyamoorthi E et al. (2023) Front Cell Infect Microbiol "Antimicrobial and antibiofilm activities of formylchromones against Vibrio parahaemolyticus and Vibrio harveyi."

Lee J, Sathiyamoorthi E, Lee JH, Tan Y

[

Front Cell Infect Microbiol,

2023]

Gram-negative Vibrio species are major foodborne pathogens often associated with seafood intake that causes gastroenteritis. On food surfaces, biofilm formation by Vibrio species enhances the resistance of bacteria to disinfectants and antimicrobial agents. Hence, an efficient antibacterial and antibiofilm approach is urgently required. This study examined the antibacterial and antivirulence effects of chromones and their 26 derivatives against V. parahaemolyticus and V. harveyi. 6-Bromo-3-formylchromone (6B3FC) and 6-chloro-3-formylchromone (6C3FC) were active antibacterial and antibiofilm compounds. Both 6B3FC and 6C3FC exhibited minimum inhibitory concentrations (MICs) of 20 µg/mL for planktonic cell growth and dose-dependently inhibited biofilm formation. Additionally, they decreased swimming motility, protease activity, fimbrial agglutination, hydrophobicity, and indole production at 20 µg/mL which impaired the growth of the bacteria. Furthermore, the active compounds could completely inhibit the slimy substances and microbial cells on the surface of the squid and shrimp. The most active compound 6B3FC inhibited the gene expression associated in quorum sensing and biofilm formation (luxS, opaR), pathogenicity (tdh), and membrane integrity (vmrA) in V. parahaemolyticus. However, toxicity profiling using seed germination and Caenorhabditis elegans models suggests that 6C3FC may have moderate effect at 50 µg/mL while 6B3FC was toxic to the nematodes 20-100 µg/mL. These findings suggest chromone analogs, particularly two halogenated formylchromones (6B3FC and 6C3FC), were effective antimicrobial and antibiofilm agents against V. parahaemolyticus in the food and pharmaceutical sectors.

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