Ropiak HM et al. (2016) J Agric Food Chem "Structure-activity relationship of condensed tannins and synergism with trans-cinnamaldehyde against Caenorhabditis elegans."

Thamsborg SM, Ropiak HM, Mueller-Harvey I, Williams AR, Ramsay A, Desrues O

[J Agric Food Chem, 2016]

Parasitic gastrointestinal nematodes (GIN) of livestock are increasingly developing resistance to synthetic nematocidal drugs. Moreover, the use of nematocides can induce ecotoxicity by affecting free-living nematodes. Condensed tannins (CT) are a structurally diverse group of bioactive plant compounds possessing anthelmintic activity against GIN. We investigated the relationship between the chemical structure of contrasting, purified CT and nematocidal effects using Caenorhabditis elegans. We also explored whether the nematocidal activity of CT could synergize with trans-cinnamaldehyde (CIN). A non-significant correlation was evident between the ability of CT fractions to inhibit C. elegans motility and the molar proportion of prodelphinidin subunits in purified CT samples. Synergistic inhibition of motility was achieved by combinations of CT and CIN. Galloylation of procyanidins was also a key factor for synergy. To increase the nematocidal effect of CT, plant sources containing CT with specific structural features could be selected and combined with compounds acting in synergy.

Kim J et al. (2017) J Ginseng Res "Effects of Korean ginseng berry on skin antipigmentation and antiaging via FoxO3a activation."

Kim J, Seo DB, Park CW, Cho D, Cho JY, Kim SH, Shimizu T, Shin SS, Cho SY, Kim S

[J Ginseng Res, 2017]

BACKGROUND: The ginseng berry has various bioactivities, including antidiabetic, anticancer, antiinflammatory, and antioxidative properties. Moreover, we have revealed that the active antiaging component of the ginseng berry, syringaresinol, has the ability to stimulate longevity via gene activation. Despite the many known beneficial effects of ginseng, its effects on skin aging are poorly understood. In this study, we investigated the effects of ginseng and the ginseng berry on one of the skin aging processes, melanogenesis, and age-related pigment lipofuscin accumulation, to elucidate the mechanism of action with respect to antiaging. METHODS: The human melanoma MNT1 cell line was treated with ginseng root extract, ginseng berry extract, or syringaresinol. Then, the cells were analyzed using a melanin assay, and the tyrosinase activity was estimated. The Caenorhabditis elegans wild type N2 strain was used for the life span assay to analyze the antiaging effects of the samples. A lipofuscin fluorescence assay was performed during 10 passages with the syringaresinol treatment. RESULTS: A 7-d treatment with ginseng berry extract reduced melanin accumulation and tyrosinase activity more than ginseng root extract. These results may be due to the active compound of the ginseng berry, syringaresinol. The antimelanogenic activity was strongly coordinated with the activation of the longevity gene foxo3a. Moreover, the ginseng berry extract had more potent antiaging effects, caused a life span extension, and reduced lipofuscin accumulation. CONCLUSION: Taken together, our results suggest that these antimelanogenic effects and antiaging effects of ginseng berry mediate the activation of antioxidation-FoxO3a signaling.

Li H et al. (2022) Sci Total Environ "Direct toxicity of environmentally persistent free radicals to nematode Caenorhabditis elegans after excluding the concomitant chemicals."

Liu Y, Li H, Steinberg C, Zuo N, Pan B, Lang D, Xing B

[Sci Total Environ, 2022]

Environmentally persistent free radicals (EPFRs) have attracted extensive attention due to their potential toxicity. However, EPFRs-containing particles always coexist with their parent organic contaminants and intermediate degradation products (IM), which may have hindered the toxicity assessment of EPFRs. In this study, the toxicity of EFFRs was specifically verified after comparing the systems without EPFRs, such as the immediate mixture of catechol (CT) and particles, solutions of CT only, IM extracted from the particles, as well as particles after EPFRs quenching. Caenorhabditis elegans (C. elegans) were used as model organisms. Our results showed that EPFRs-containing particles (Si-Al-CT) exhibited significant toxicity to C. elegans, but not for the parent chemical CT and IM on the particles. Higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the Si-Al-CT system were attributed to the mediated generation of -O₂^- and -OH via EPFRs. EPFRs could increase gene expressions related not only to oxidative stress and biotransformation in C. elegans, but also to indications of disturbances in energy homeostasis, survival, proliferation, cell and embryonic development. Overall, these results confirmed the direct toxicity of EPFRs and highlighted the key role of EPFRs which may be neglected in assessing the environmental risks of organic contaminants.

Bjork P et al. (2002) Mol Biol Cell "A novel conserved RNA-binding domain protein, RBD-1, is essential for ribosome biogenesis."

Wieslander L, Burglin TR, Tong YG, Bauren G, Hellman U, Bjork P, Jin S

[Mol Biol Cell, 2002]

Synthesis of the ribosomal subunits from pre-rRNA requires a large number of trans-acting proteins and small nucleolar ribonucleoprotein particles to execute base modifications, RNA cleavages, and structural rearrangements. We have characterized a novel protein, RNA-binding domain-1 (RBD-1), that is involved in ribosome biogenesis. This protein contains six consensus RNA-binding domains and is conserved as to sequence, domain organization, and cellular location from yeast to human. RBD-1 is essential in Caenorhabditis elegans. In the dipteran Chironomus tentans, RBD-1 (Ct-RBD-1) binds pre-rRNA in vitro and anti-Ct-RBD-1 antibodies repress pre-rRNA processing in vivo. Ct-RBD-1 is mainly located in the nucleolus in an RNA polymerase I transcription-dependent manner, but it is also present in discrete foci in the interchromatin and in the cytoplasm. In cytoplasmic extracts, 20-30% of Ct-RBD-1 is associated with ribosomes and, preferentially, with the 40S ribosomal subunit. Our data suggest that RBD-1 plays a role in structurally coordinating pre-rRNA during ribosome biogenesis and that this function is conserved in all eukaryotes.

Katiki LM et al. (2013) Vet Parasitol "Anthelmintic effect of plant extracts containing condensed and hydrolyzable tannins on Caenorhabditis elegans, and their antioxidant capacity."

Chagas AC, Lindsay DS, Zajac AM, Gonzalez JM, Amarante AF, Ferreira JF, Katiki LM

[Vet Parasitol, 2013]

Although tannin-rich forages are known to increase protein uptake and to reduce gastrointestinal nematode infections in grazing ruminants, most published research involves forages with condensed tannins (CT), while published literature lacks information on the anthelmintic capacity, nutritional benefits, and antioxidant capacity of alternative forages containing hydrolyzable tannins (HT). We evaluated the anthelmintic activity and the antioxidant capacity of plant extracts containing either mostly CT, mostly HT, or both CT and HT. Extracts were prepared with 70% acetone, lyophilized, redissolved to doses ranging from 1.0mg/mL to 25mg/mL, and tested against adult Caenorhabditis elegans as a test model. The extract concentrations that killed 50% (LC(50)) or 90% (LC(90)) of the nematodes in 24h were determined and compared to the veterinary anthelmintic levamisole (8 mg/mL). Extracts were quantified for CT by the acid butanol assay, for HT (based on gallic acid and ellagic acid) by high-performance liquid chromatography (HPLC) and total phenolics, and for their antioxidant activity by the oxygen radical absorbance capacity (ORAC) assay. Extracts with mostly CT were Lespedeza cuneata, Salix X sepulcralis, and Robinia pseudoacacia. Extracts rich in HT were Acer rubrum, Rosa multiflora, and Quercus alba, while Rhus typhina had both HT and CT. The extracts with the lowest LC(50) and LC(90) concentrations, respectively, in the C. elegans assay were Q. alba (0.75 and 1.06 mg/mL), R. typhina collected in 2007 (0.65 and 2.74 mg/mL), A. rubrum (1.03 and 5.54 mg/mL), and R. multiflora (2.14 and 8.70 mg/mL). At the doses of 20 and 25mg/mL, HT-rich, or both CT- and HT-rich, extracts were significantly more lethal to adult C. elegans than extracts containing only CT. All extracts were high in antioxidant capacity, with ORAC values ranging from 1800 moles to 4651 moles of trolox equivalents/g, but ORAC did not correlate with anthelmintic activity. The total phenolics test had a positive and highly significant (r=0.826, p 0.01) correlation with total hydrolyzable tannins. Plants used in this research are naturalized to the Appalachian edaphoclimatic conditions, but occur in temperate climate areas worldwide. They represent a rich, renewable, and unexplored source of tannins and antioxidants for grazing ruminants, whereas conventional CT-rich forages, such as L. cuneata, may be hard to establish and adapt to areas with temperate climate. Due to their high in vitro anthelmintic activity, antioxidant capacity, and their adaptability to non-arable lands, Q. alba, R. typhina, A. rubrum, and R. multiflora have a high potential to improve the health of grazing animals and must have their anthelmintic effects confirmed in vivo in both sheep and goats.

Zhou H et al. (2021) Front Nutr "Lycium barbarum Extracts Extend Lifespan and Alleviate Proteotoxicity in Caenorhabditis elegans."

Zhou H, Sun C, Wang CC, Fu J, Ding S, Wang X, Yang D, Wang L

[Front Nutr, 2021]

Lycium barbarum berry (Ningxia Gouqi, Fructus lycii, goji berry, or wolfberry), as a traditional Chinese herb, was recorded beneficial for longevity in traditional Chinese medical scriptures and currently is a natural dietary supplement worldwide. However, under modern experimental conditions, the longevity effect of L. barbarum berry and the underlying mechanisms have been less studied. Here, we reported that total water extracts of L. barbarum berry (LBE), which contains 22% polysaccharides and other components, such as anthocyanins, extended the lifespan of Caenorhabditis elegans without side effects on worm fertility and pharyngeal pumping. Interestingly, we found that the lifespan extension effect was more prominent in worms with shorter mean lifespan as compared to those with longer mean lifespan. Furthermore, we showed that the lifespan extension effect of LBE depended on deacetylase sir-2.1. Remarkably, LBE rescued heat shock transcription factor-1 (hsf-1) deficiency in wild-type worms with different mean lifespans, and this effect also depended on sir-2.1. In addition, we found that LBE extended lifespan and alleviated toxic protein aggregation in neurodegenerative worms with hsf-1 deficiency. Our study suggested that LBE may be a potential antiaging natural dietary supplement especially to individuals with malnutrition or chronic diseases and a potential therapeutic agent for neurodegenerative diseases characterized by hsf-1 deficiency.

Cinar HN et al. (2010) PLoS One "Vibrio cholerae hemolysin is required for lethality, developmental delay, and intestinal vacuolation in Caenorhabditis elegans."

Datta AR, Tall BD, Kothary M, Yildiz F, Cinar HN, Sprando R, McCardell B, Bilecen K

[PLoS One, 2010]

BACKGROUND: Cholera toxin (CT) and toxin-co-regulated pili (TCP) are the major virulence factors of Vibrio cholerae O1 and O139 strains that contribute to the pathogenesis of disease during devastating cholera pandemics. However, CT and TCP negative V. cholerae strains are still able to cause severe diarrheal disease in humans through mechanisms that are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: To determine the role of other virulence factors in V. cholerae pathogenesis, we used a CT and TCP independent infection model in the nematode Caenorhabditis elegans and identified the hemolysin A (hlyA) gene as a factor responsible for animal death and developmental delay. We demonstrated a correlation between the severity of infection in the nematode and the level of hemolytic activity in the V. cholerae biotypes. At the cellular level, V. cholerae infection induces formation of vacuoles in the intestinal cells in a hlyA dependent manner, consistent with the previous in vitro observations. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that HlyA is a virulence factor in C. elegans infection leading to lethality and developmental delay presumably through intestinal cytopathic changes.

Chen X et al. (2012) Science "Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes."

Su Z, Shi S, Yang J, Chen Z, Chen H, Lin F, He X, Chen X

[Science, 2012]

It is unknown how the composition and structure of DNA within the cell affect spontaneous mutations. Theory suggests that in eukaryotic genomes, nucleosomal DNA undergoes fewer CT mutations because of suppressed cytosine hydrolytic deamination relative to nucleosome-depleted DNA. Comparative genomic analyses and a mutation accumulation experiment showed that nucleosome occupancy nearly eliminated cytosine deamination, resulting in an ~50% decrease of the CT mutation rate in nucleosomal DNA. Furthermore, the rates of GT and AT mutations were also about twofold suppressed by nucleosomes. On the basis of these results, we conclude that nucleosome-dependent mutation spectra affect eukaryotic genome structure and evolution and may have implications for understanding the origin of mutations in cancers and in induced pluripotent stem cells.

Greene BM et al. (1983) Clin Exp Immunol "Non-specific suppression of antigen-induced lymphocyte blastogenesis in Onchocerca volvulus infection in man."

Greene BM, Fanning MM, Ellner JJ

[Clin Exp Immunol, 1983]

Lymphocyte blastogenic responses to O. volvulus antigen (Oncho Ag), SKSD, and the mitogen PHA were tested in three groups of persons: light to moderately infected persons (INF); previously exposed but uninfected persons (EXP) and normal controls (NC). The exposed group showed significant responsiveness to Oncho Ag (delta ct/min = 6,002 +/- 1,375), while the infected (delta ct/min = 943 +/- 418) and normal control (delta ct/min = 428 +/- 418) groups did not. The mean blastogenic response to SKSD were EXP, 8,644 +/- 5,249; NC 6,039 +/- 2,880; INF, 2,619 +/- 1,012. The reduced reactivity in the INF group to Oncho Ag showed a significant correlation with reactivity to SKSD (P less than 0.05). To elucidate the mechanism of hyporesponsiveness in the infected group rigorous adherent cell depletion, by adherence to plastic followed by a nylon wool column, was utilized. When 20% plastic adherent cells were added back to the T cells prepared in this fashion, the mean blastogenic response to SKSD was significantly augmented (P less than 0.01). In contrast, the responsiveness to Oncho Ag was not significantly altered. The addition of indomethacin (1 microgram/ml) or autologous plasma had no significant effect on reactivity to either SKSD or Oncho Ag. There were no significant differences in the mean reactivity of the three groups to PHA-M (delta ct/min EXP 78,514 +/- 12,564; INF 62,393 +/- 14,447; NC 61,423 +/- 4,465). These results suggest that O. volvulus infection is associated with decreased lymphocyte reactivity to both parasite related and unrelated antigens, and imply that the mechanism for the two types of hyporesponsiveness may be distinct. While a weakly adherent suppressor cell may account for non-specific hyporesponsiveness, the mechanism of parasite specific decreased reactivity remains unknown.

Camacho-Aguilar E et al. (2021) PLoS Comput Biol "Quantifying cell transitions in C. elegans with data-fitted landscape models."

Rand DA, Warmflash A, Camacho-Aguilar E

[PLoS Comput Biol, 2021]

Increasing interest has emerged in new mathematical approaches that simplify the study of complex differentiation processes by formalizing Waddington's landscape metaphor. However, a rational method to build these landscape models remains an open problem. Here we study vulval development in C. elegans by developing a framework based on Catastrophe Theory (CT) and approximate Bayesian computation (ABC) to build data-fitted landscape models. We first identify the candidate qualitative landscapes, and then use CT to build the simplest model consistent with the data, which we quantitatively fit using ABC. The resulting model suggests that the underlying mechanism is a quantifiable two-step decision controlled by EGF and Notch-Delta signals, where a non-vulval/vulval decision is followed by a bistable transition to the two vulval states. This new model fits a broad set of data and makes several novel predictions.