Cross HF et al. (2001) Lancet "Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood."

Haarbrink M, Taylor MJ, Cross HF, Yazdanbakhsh M, Egerton G

[Lancet, 2001]

Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hosts. Studies in mice have suggested that these bacteria are associated with systemic inflammatory reactions to filarial chemotherapy. We took blood samples from 15 Indonesian patients before and after treatment with diethylcarbamazine for Brugia malayi infection, and recorded the severity of any post-treatment inflammatory reactions. Blood from all three patients with severe adverse reactions and from one of six with moderate reactions was positive for Wolbachia DNA 4-48 h after diethylcarbamazine treatment. We suggest that these severe inflammatory reactions are associated with the release of endosymbionts into the blood after treatment for filariasis.

Zhou W et al. (2017) Nan Fang Yi Ke Da Xue Xue Bao "[Effect of Herba Scutellariae Barbatae flavonoids in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells in vitro]."

Lin HZ, Lin JM, Wang SL, Zhou W

[Nan Fang Yi Ke Da Xue Xue Bao, 2017]

OBJECTIVE: To explore the effects of Herba Scutellariae Barbatae flavonoids (HF) in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: The effects of 30 or 50 mg/L of HF on nematode life span, reproductive capacity, oxidative stress, and antioxidant enzyme activity of C. elegans were assessed, and the effects of HF on the expressions of the genes encoding antioxidant enzymes and the aging-related genes were analyzed using real-time RT-PCR in both C. elegans and cultured HUVECs. Results Compared with the blank control group, C. elegans with HF treatment showed significantly improved mean and maximum lifespan with a prolonged mean lifespan under acute heat stress at 35 degrees celsius;. HF treatment did not impair the reproductive capacity or cause significant changes in the offspring number of C. elegans. In addition, HF enhanced SOD and CAT activity and up-regulated the expression of daf-16 and sir-2.1 (SIRT1) genes in C. elegans and HUVECs. CONCLUSIONS: HF may delay aging of C. elegans and enhance their resistance to acute heat stress without damaging their reproductive capacity possibly by up-regulating the activity of antioxidant enzymes and expressions of antioxidant genes. HF also may protect endothelial cells against oxidative damage.

Menzel R et al. (2012) Front Genet "The Nematode Caenorhabditis elegans, Stress and Aging: Identifying the Complex Interplay of Genetic Pathways Following the Treatment with Humic Substances."

Tiedt S, Witczak J, Menzel S, Sturzenbaum SR, Swain SC, Steinberg CE, Menzel R, Pietsch K

[Front Genet, 2012]

Low concentrations of the dissolved leonardite humic acid HuminFeed() (HF) prolonged the lifespan and enhanced the thermal stress resistance of the model organism Caenorhabditis elegans. However, growth was impaired and reproduction delayed, effects which have also been identified in response to other polyphenolic monomers, including Tannic acid, Rosmarinic acid, and Caffeic acid. Moreover, a chemical modification of HF, which increases its phenolic/quinonoid moieties, magnified the biological impact on C. elegans. To gain a deep insight into the molecular basis of these effects, we performed global transcriptomics on young adult (3days) and old adult (11days) nematodes exposed to two different concentrations of HF. We also studied several C. elegans mutant strains in respect to HF derived longevity and compared all results with data obtained for the chemically modified HF. The gene expression pattern of young HF-treated nematodes displayed a significant overlap to other conditions known to provoke longevity, including various plant polyphenol monomers. Besides the regulation of parts of the metabolism, transforming growth factor-beta signaling, and Insulin-like signaling, lysosomal activities seem to contribute most to HF's and modified HF's lifespan prolonging action. These results support the notion that the phenolic/quinonoid moieties of humic substances are major building blocks that drive the physiological effects observed in C. elegans.

Qu X et al. (2019) Chemistry "Metal-Organic Frameworks Harness Cu Chelating and Photooxidation Against Amyloid Aggregation in vivo."

Guan Y, Qu X, Ren J, Bai F, Gao N, Du Z, Yu D

[Chemistry, 2019]

Nowadays, photooxygenation of A has emerged as an effective way to inhibit A aggregation in AD treatment. However, their further application has been highly obstructed by self-aggregate, no metal chelating ability and poor protein enrichment capacity. Herein, porphyrinic metal-organic frameworks (PMOFs) are utilized as a super Cu (II) chelating and photooxidation agent for inhibiting A aggregation. We selected only four classical kinds of POMFs (Zr-MOF, Al-MOF, Ni-MOF, Hf-MOF) for further investigation in our study, which are stable in physiological condition and exhibit excellent biocompatibility. Among them, Hf-MOF becomes the most efficient A photooxidant and a possible explanation about the difference in capacity of 1O2 generation of these four PMOFs has been provided according to the experimental results and DFT calculations. Furthermore, Hf-MOFs are modified with A-targeting peptide, LPFFD. This can not only enhance Hf-MOFs targeting cellular A to decrease A-induced cytotoxicity, but also improve A photooxidation in the complicated living environment. More intriguingly, in vivo studies indicate that the well-designed LPFFD modified Hf-MOFs can decrease A-induced neurotoxicity and extend the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Our work may open a new avenue for using MOFs as neurotoxic-metal chelating and photo-therapeutic agents for AD treatment.

Taylor MJ et al. (2000) J Exp Med "Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria."

Cross HF, Taylor MJ, Bilo K

[J Exp Med, 2000]

The pathogenesis of filarial disease is characterized by acute and chronic inflammation. Inflammatory responses are thought to be generated by either the parasite, the immune response, or opportunistic infection. We show that soluble extracts of the human filarial parasite Brugia malayi can induce potent inflammatory responses, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO) from macrophages. The active component is heat stable, reacts positively in the Limulus amebocyte lysate assay, and can be inhibited by polymyxin B. TNF-alpha, IL-1beta, and NO responses were not induced in macrophages from lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice. The production of TNF-alpha after chemotherapy of microfilariae was also only detected in LPS-responsive C3H/HeN mice, suggesting that signaling through the Toll-like receptor 4 (TLR4) is necessary for these responses. We also show that CD14 is required for optimal TNF-alpha responses at low concentrations. Together, these results suggest that extracts of B. malayi contain bacterial LPS. Extracts from the rodent filaria, Acanthocheilonema viteae, which is not infected with the endosymbiotic Wolbachia bacteria found in the majority of filarial parasites, failed to induce any inflammatory responses from macrophages, suggesting that the source of bacterial LPS in extracts of B. malayi is the Wolbachia endosymbiont. Wolbachia extracts derived from a mosquito cell line induced similar LPS-dependent TNF-alpha and NO responses from C3H/HeN macrophages, which were eliminated after tetracycline treatment of the bacteria. Thus, Wolbachia LPS may be one of the major mediators of inflammatory pathogenesis in filarial nematode disease.

Nawa Y et al. (1982) J Parasitol "Stage-specific cross-resistance between Nippostrongylus brasiliensis and Strongyloides ratti (Nematoda) in rats."

Tada I, Nawa Y, Korenaga M, Mimori T

[J Parasitol, 1982]

Stage-specificity of cross-resistance between Nippostrongylus brasiliensis and Strongyloides ratti was investigated. Results showed that immunization with tissue-migrating larvae was sufficient to generate cross-resistance and that host defense mechanisms operating in the cross-resistance were directed against tissue-migrating larvae but not against intestinal adult worms. In addition, no significant potentiation of the cross-resistance was observed after multiple immunization. These observations suggest that host defense mechanisms against heterologous challenge infection were qualitatively and/or quantitatively different from those against homologous challenge infection.

Parise G et al. (1997) Biochim Biophys Acta "Assembly of nematode cuticle: role of hydrophobic interactions in CUT-2 cross-linking."

Bazzicalupo P, Parise G

[Biochim Biophys Acta, 1997]

CUT-2 is a component of cuticlin, the highly cross-linked, insoluble residue of the cuticle of the nematode Caenorhabditis elegans. A recombinant fragment of CUT-2, produced in E. coli, can be cross-linked in vitro by horse radish peroxidase via dityrosine formation to give large molecular species [1]. In this paper it is shown that the formation of CUT-2 polymers is greatly favoured over that of CUT-2 oligomers as no low molecular weight intermediates, dimers or trimers can be detected even when the cross-linking reaction is slowed or interrupted before completion. This suggests that recombinant CUT-2 forms large non-covalent complexes that are the only competent substrate for cross-linking. The inhibition of cross-linking by urea and the behavior of recombinant CUT-2 in size-exclusion chromatography under a variety of conditions suggest that hydrophobic interactions are important in the formation and stabilization of these complexes. The complexes are excellent substrates for cross-linking but react poorly with free tyrosine. In contrast, a soluble recombinant CUT-2 is a poor substrate for cross-linking but can efficiently react with free tyrosine.

Yang B et al. (2012) Nat Methods "Identification of cross-linked peptides from complex samples."

He SM, Zhang K, Li S, Chen HF, Wang LH, Hao Z, Wu YJ, Li YX, Chi H, Zhu M, Yang B, Chen S, Lin J, Ye K, Xiu LY, Ding YH, Fan SB, Luo SK, Dong MQ

[Nat Methods, 2012]

We have developed pLink, software for data analysis of cross-linked proteins coupled with mass-spectrometry analysis. pLink reliably estimates false discovery rate in cross-link identification and is compatible with multiple homo- or hetero-bifunctional cross-linkers. We validated the program with proteins of known structures, and we further tested it on protein complexes, crude immunoprecipitates and whole-cell lysates. We show that it is a robust tool for protein-structure and protein-protein-interaction studies.

Rabinowitch I et al. (2016) Commun Integr Biol "The foundations of cross-modal plasticity."

Bai J, Rabinowitch I

[Commun Integr Biol, 2016]

Cross-modal plasticity is a striking adaptive feature of the brain, whereby the loss of one sensory modality induces cortical reorganization that leads to enhanced sensory performance in remaining modalities. Much is known about the macroscopic modifications in the brain that underly cross-modal plasticity and the associated changes in sensory performance. In contrast there is relatively scant information about the molecular and cellular underpinnings of this mechanism. We hypothesized that cross-modal plasticity is a fundamental feature of the nervous system. As such, it should be found in organisms with brains that are substantially less complex than our own. Indeed, we discovered a cross-modal plasticity mechanism in the roundworm Caenorhabditis elegans, whose nervous system is composed of only 302 neurons. Taking advantage of the simplicity of the C. elegans nervous system, we were able to comprehensively study cross-modal plasticity from molecule through circuit to behavior.

Menzel R et al. (2011) Environ Sci Technol "Enrichment of humic material with hydroxybenzene moieties intensifies its physiological effects on the nematode Caenorhabditis elegans."

Menzel R, Bahrs H, Kubsch G, Steinberg CE, Menzel S, Tiedt S, Putschew A, StoBer R, Saul N

[Environ Sci Technol, 2011]

Dissolved humic substances are taken up by organisms and interact on various molecular and biochemical levels. In the nematode Caenorhabditis elegans, such material can promote longevity and increase its reproductive capacity; moreover, the worms tend to stay for longer in humic-enriched environments. Here, we tested the hypothesis that the chemical enrichment of humic substances with hydroxybenzene moieties intensifies these physiological effects. Based on the leonardite humic acid HuminFeed (HF), we followed a polycondensation reaction in which this natural humic substance and a dihydroxybenzene (hydroquinone or benzoquinone) served as reaction partners. Several analytical methods showed the formation of the corresponding copolymers. The chemical modification boosted the antioxidant properties of HF both in vitro and in vivo. Humic substances enriched with hydroxybenzene moieties caused a significantly increased tolerance to thermal stress in C. elegans and extended its lifespan. Exposed nematodes showed delayed linear growth and onset of reproduction and a stronger pumping activity of the pharynx. Thus, treated nematodes act younger than they really are. In this feature the modified HF replicated the biological impact of hydroquinone-homopolymers and various plant polyphenol monomers, thereby supporting the hydroxybenzene moieties of humic substances as major effective structures for the physiological effects observed in C. elegans.