- Evolving Therapy for Celiac Disease. [Review]
- FPFront Pediatr 2019; 7:193
- Gluten is known to be the main triggering factor for celiac disease (CeD), an immune-mediated disorder. CeD is therefore managed using a strict and lifelong gluten-free diet (GFD), the only effective…
Gluten is known to be the main triggering factor for celiac disease (CeD), an immune-mediated disorder. CeD is therefore managed using a strict and lifelong gluten-free diet (GFD), the only effective treatment available currently. However, the GFD is restrictive. Hence, efforts are being made to explore alternative therapies. Based on their mechanisms of action on various molecular targets involved in the pathogenesis of CeD, these therapies may be classified into one of the following five broad approaches. The first approach focuses on decreasing the immunogenic content of gluten, using strategies like genetically modified wheat, intra-intestinal gluten digestion using glutenases, microwave thermal treatment of hydrated wheat kernels, and gluten pretreatment with either bacterial/ fungal derived endopeptidases or microbial transglutaminase. The second approach involves sequestering gluten in the gut lumen before it is digested into immunogenic peptides and absorbed, using binder drugs like polymer p(HEMA-co-SS), single chain fragment variable (scFv), and anti- gluten antibody AGY. The third approach aims to prevent uptake of digested gluten through intestinal epithelial tight junctions, using a zonulin antagonist. The fourth approach involves tissue transglutaminase (tTG) inhibitors to prevent the enhancement of immunogenicity of digested gluten by the intestinal tTG enzyme. The fifth approach seeks to prevent downstream immune activation after uptake of gluten immunogenic peptides through the intestinal mucosal epithelial layer. Examples include HLA-DQ2 blockers that prevent presentation of gluten derived- antigens by dendritic cells to T cells, immune- tolerizing therapies like the vaccine Nexvax2 and TIMP-Glia, cathepsin inhibitors, immunosuppressants like corticosteroids, azathioprine etc., and anti-cytokine agents targeting TNF-α and interleukin-15. Apart from these approaches, research is being done to evaluate the effectiveness of probiotics/prebiotics, helminth therapy using Necator americanus, low FODMAP diet, and pancreatic enzyme supplementation in CeD symptom control; however, the mechanisms by which they play a beneficial role in CeD are yet to be clearly established. Overall, although many therapies being explored are still in the pre-clinical phase, some like the zonulin antagonist, immune tolerizing therapies and glutenases have reached phase II/III clinical trials. While these potential options appear exciting, currently they may at best be used to supplement rather than supplant the GFD.
- Helminth Therapy - From the Parasite Perspective. [Review]
- TPTrends Parasitol 2019 May 29
- Studies in animal models and humans suggest that intentional exposure to helminths or helminth-derived products may hold promise for treating chronic inflammatory-associated diseases (CIADs). Althoug…
Studies in animal models and humans suggest that intentional exposure to helminths or helminth-derived products may hold promise for treating chronic inflammatory-associated diseases (CIADs). Although the mechanisms underlying 'helminth therapy' are being evaluated, little attention has been paid to the actual organisms in use. Here we examine the notion that, because of the complexity of biological symbiosis, intact helminths rather than helminth-derived products are likely to prove more useful for clinical purposes. Further, weighing potential cost/benefit ratios of various helminths along with other factors, such as feasibility of production, we argue that the four helminths currently in use for CIAD treatments in humans were selected more by happenstance than by design, and that other candidates not yet tested may prove superior.
- Diagnosis of soil-transmitted helminth infections. An unsolved problemin the omics era. [Journal Article]
- EIEnferm Infecc Microbiol Clin 2019; 37 Suppl 1:20-25
- Infections caused by Strongyloides stercoralis and other soil-transmitted worms such as hookworms (Necator americanus and Ancylostoma duodenale) represent a major problem worldwide, especially in dev…
Infections caused by Strongyloides stercoralis and other soil-transmitted worms such as hookworms (Necator americanus and Ancylostoma duodenale) represent a major problem worldwide, especially in developing areas. They are difficult to suspect clinically since they produce non-specific and often overlapping signs and symptoms. Likewise, their long prepatent periods hamper the detection of parasitic structures. Microscopic diagnosis is still the most commonly used tool in healthcare laboratories but it is still far from being the ideal technique to detect these infections due to its low sensitivity. In addition, these nematodes have strong morphologic similarities and consequently microbiological diagnosis remains a challenge. Serology has made progress in the diagnosis of S. stercoralis infection but this option is not yet available for hookworms. Molecular biology techniques have been shown to slightly increase this lack of sensitivity, but as with other parasitic infections, they are not currently available for use in clinical microbiology laboratories. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A. © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.
- De novo transcriptome assembly of a facultative parasitic nematode Pelodera (syn. Rhabditis) strongyloides. [Journal Article]
- GENEGene 2019 May 23; 710:30-38
- Pelodera strongyloides is a generally free-living gonochoristic facultative nematode. The whole genomic sequence of P. strongyloides remains unknown but 4 small subunit ribosomal RNA (ssrRNA) gene se…
Pelodera strongyloides is a generally free-living gonochoristic facultative nematode. The whole genomic sequence of P. strongyloides remains unknown but 4 small subunit ribosomal RNA (ssrRNA) gene sequences are available. This project launched a de novo transcriptome assembly with 100 bp paired-end RNA-seq reads from normal, starved and wet-plate cultured animals. Trinity assembly tool generated 104,634 transcript contigs with N50 contig being 2195 bp and average contig length at 1103 bp. Transcriptome BLASTX matching results of five nematodes (C. elegans, Strongyloides stercoralis, Necator americanus, Trichuris trichiura, and Pristionchus pacificus) were consistent with their evolutionary relationships. Sixteen genes were identified to be homologous to key elements of the C. elegans RNA interference system, such as Dicer, Argonaute, RNA-dependent RNA polymerase and double strand RNA transport proteins. In starved samples, we observed up-regulation of cuticle related genes and 3 dauer formation genes. Dauer morphology was captured with enlarged phasmid under light microscopy, and dauer and normal larvae counts in clumps had a Pearson's product-moment correlation of 0.805 with P-value = 0.0088. Our results demonstrate that P. strongyloides could be used for studying nematode-related human or pet parasitic diseases. The sequenced assembled transcriptome reported here may be useful to understand the evolution of parasitism in Nematoda.
- Application of thermo-separating aqueous two-phase system in extractive bioconversion of polyhydroxyalkanoates by Cupriavidus necator H16. [Journal Article]
- BTBioresour Technol 2019; 287:121474
- Polyhydroxyalkanoates (PHAs), a family of biodegradable and renewable biopolymers show a huge potential as an alternative to conventional plastics. Extractive bioconversion (in situ product recovery)…
Polyhydroxyalkanoates (PHAs), a family of biodegradable and renewable biopolymers show a huge potential as an alternative to conventional plastics. Extractive bioconversion (in situ product recovery) is a technique that integrates upstream fermentation and downstream purification. In this study, extractive bioconversion of PHAs from Cupriavidus necator H16 was performed via a thermo-separating aqueous two-phase system to reduce the cost and environmental impacts of PHAs production. Key operating parameters, such as polymer concentration, temperature, and pH, were optimized. The strategy achieved a yield and PF of 97.6% and 1.36-fold, respectively at 5% EOPO 3900 concentration, 30 °C fermentation temperature and pH 6. The PHAs production process was also successfully scaled up in a 2 L bioreactor. To the best of our knowledge, this is the first report on extractive fermentation of PHAs from Cupriavidus necator utilizing a thermo-separation system to achieve a better productivity and purity of the target product.
- Synthesis of Polyhydroxyalkanoates by Hydrogen-Oxidizing Bacteria in a Pilot Production Process. [Journal Article]
- BBiomacromolecules 2019 May 23
- The synthesis of polyhydroxyalkanoates (PHAs) was scaled up to pilot production in a 150-L fermenter on sugars (fructose and glucose) and purified and crude glycerol in a culture of the wild-type str…
The synthesis of polyhydroxyalkanoates (PHAs) was scaled up to pilot production in a 150-L fermenter on sugars (fructose and glucose) and purified and crude glycerol in a culture of the wild-type strain Cupriavidus necator B-10646. Over 60 h of cultivation, a cell concentration of 150-160 g/L was obtained on purified glycerol and glucose; cultivation on fructose and crude glycerol resulted in a cell concentration of 130 ± 10 g/L. Polymer content and yield coefficients for the biomass were similar on all substrates (80-85 wt % and 0.29-0.33 kg biomass/kg carbon substrate, respectively). Copolymers poly(3-hydroxybutyrate- co-3-hydroxyvalerate) and poly(3-hydroxybutyrate- co-4-hydroxybutyrate) and terpolymers poly(3-hydroxybutyrate- co-3-hydroxyvalerate- co-4-hydroxybutyrate) having a decreased degree of crystallinity (36-46%) were first synthesized in the scaled-up process using C. necator B-10646 cultivated on glycerol. These results will provide the basis for scaling-up PHA synthesis in an organotrophic C. necator B-10646 culture.
- Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections. [Journal Article]
- PVParasit Vectors 2019 May 14; 12(1):226
- CONCLUSIONS: Emodepside is highly active against a broad range of nematode species both in vitro and in vivo. The development of emodepside for treating soil-transmitted helminth infections should be pursued.
- Horizontal acquisition of hydrogen conversion ability and other habitat adaptations in the Hydrogenovibrio strains SP-41 and XCL-2. [Journal Article]
- BGBMC Genomics 2019 May 06; 20(1):339
- CONCLUSIONS: Our results suggest that horizontal gene transfer plays an important role in shaping the genomes of these strains, as a likely mechanism for habitat adaptation, including, but not limited to the transfer of the hydrogen conversion ability.
- Characterization of a non-sexual population of Strongyloides stercoralis with hybrid 18S rDNA haplotypes in Guangxi, Southern China. [Journal Article]
- PNPLoS Negl Trop Dis 2019; 13(5):e0007396
- Strongyloidiasis is a much-neglected but sometimes fatal soil born helminthiasis. The causing agent, the small intestinal parasitic nematode Strongyloides stercoralis can reproduce sexually through t…
Strongyloidiasis is a much-neglected but sometimes fatal soil born helminthiasis. The causing agent, the small intestinal parasitic nematode Strongyloides stercoralis can reproduce sexually through the indirect/heterogonic life cycle, or asexually through the auto-infective or the direct/homogonic life cycles. Usually, among the progeny of the parasitic females both, parthenogenetic parasitic (females only) and sexual free-living (females and males) individuals, are present simultaneously. We isolated S. stercoralis from people living in a village with a high incidence of parasitic helminths, in particular liver flukes (Clonorchis sinensis) and hookworms, in the southern Chinese province Guangxi. We determined nuclear and mitochondrial DNA sequences of individual S. stercoralis isolated from this village and from close by hospitals and we compared these S. stercoralis among themselves and with selected published S. stercoralis from other geographic locations. For comparison, we also analyzed the hookworms present in the same location. We found that, compared to earlier studies of S. stercoralis populations in South East Asia, all S. stercoralis sampled in our study area were very closely related, suggesting a recent common source of infection for all patients. In contrast, the hookworms from the same location, while all belonging to the species Necator americanus, showed rather extensive genetic diversity even within host individuals. Different from earlier studies conducted in other geographic locations, almost all S. stercoralis in this study appeared heterozygous for different sequence variants of the 18S rDNA hypervariable regions (HVR) I and IV. In contrast to earlier investigations, except for three males, all S. stercoralis we isolated in this study were infective larvae, suggesting that the sampled population reproduces predominantly, if not exclusively through the clonal life cycles. Consistently, whole genome sequencing of individual worms revealed higher heterozygosity than reported earlier for likely sexual populations of S. stercoralis. Elevated heterozygosity is frequently associated with asexual clonal reproduction.
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- Modified Harada-Mori and simple wet mount to determine hookworm infections in Yo Island urban area, Songkhla, Southern Thailand. [Journal Article]
- TMTrop Med Health 2019; 47:27
- CONCLUSIONS: Parasite prevalence was low in this urban community of mostly low-income village dwellers. The mHMFPC appeared better at detecting hookworm but numbers were small. Combined techniques are suitable for field use.