Revisiting glucose uptake and metabolism in schistosomes: new molecular insights for improved schistosomiasis therapies.
Ontology highlight
ABSTRACT:
SUBMITTER: You H
PROVIDER: S-EPMC4052099 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.
| S-EPMC8148369 | biostudies-literature
Project description:Metastatic melanoma has historically been considered as one of the most therapeutically challenging malignancies. However, for the first time after decades of basic research and clinical investigation, new drugs have produced major clinical responses. The discovery of BRAF mutations in melanoma created the first opportunity to develop oncogene-directed therapy in this disease and led to the development of compounds that inhibit aberrant BRAF activity. A decade later, vemurafenib, an orally available and well-tolerated selective BRAF inhibitor, ushered in a new era of molecular treatments for advanced disease. Additional targets have been identified, and novel agents that impact on various signaling pathways or modulate the immune system hold the promise of a whole new therapeutic landscape for patients with metastatic melanoma. One of the major thrusts in melanoma therapy is now focused on understanding and targeting the network of signal transduction pathways and on attacking elements that underlie the tumor's propensity for growth and chemoresistance. In this article, we review the novel targeted anticancer approaches that are under consideration in melanoma treatment.
| S-EPMC3759013 | biostudies-literature
Project description:Metabolism encompasses the biochemical processes that allow healthy cells to keep energy, redox balance and building blocks required for cell development, survival, and proliferation steady. Malignant cells are well-documented to reprogram their metabolism and energy production networks to support rapid proliferation and survival in harsh conditions via mutations in oncogenes and inactivation of tumor suppressor genes. Despite the histologic and genetic heterogeneity of tumors, a common set of metabolic pathways sustain the high proliferation rates observed in cancer cells. This review with a focus on lung cancer covers several fundamental principles of the disturbed glucose metabolism, such as the "Warburg" effect, the importance of the glycolysis and its branching pathways, the unanticipated gluconeogenesis and mitochondrial metabolism. Furthermore, we highlight our current understanding of the disturbed glucose metabolism and how this might result in the development of new treatments.
| S-EPMC6873590 | biostudies-literature
Project description:Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).
| S-EPMC9698532 | biostudies-literature
Project description:The need to discover new treatments for human schistosomiasis has been an important driver for molecular research on schistosomes, a major breakthrough being the publication of the Schistosoma mansoni and Schistosoma japonicum genomes in 2009. This 'Primer' considers recent advances in the understanding of schistosome biology by providing a snapshot of selected areas of contemporary functional schistosome research, including that on the genome, the tegument, cell signalling and developmental biology, offering biologists a valuable insight into the life of these fascinating parasites at the basic and molecular level.
| S-EPMC3206467 | biostudies-literature
Project description:The freshwater snail Biomphalaria glabrata is an important intermediate host of the parasite Schistosoma mansoni that causes human intestinal schistosomiasis. To better understand vector snail biology and help advance innovative snail control strategies, we have developed a new snail model consisting of two homozygous B. glabrata lines (iM line and iBS90) with sharply contrasting schistosome-resistance phenotypes. We produced and compared high-quality genome sequences for iM line and iBS90 which were assembled from 255 (N50 = 22.7 Mb) and 346 (N50 = 19.4 Mb) scaffolds, respectively. Using F2 offspring bred from the two lines and the newly generated iM line genome, we constructed 18 linkage groups (representing the 18 haploid chromosomes) covering 96% of the genome and identified three new QTLs (quantitative trait loci), two involved in snail resistance/susceptibility and one relating to body pigmentation. This study provides excellent genomic resources for unveiling complex vector snail biology, reveals genomic difference between resistant and susceptible lines, and offers novel insights into genetic mechanism of the compatibility between snail and schistosome.
| S-EPMC9463173 | biostudies-literature
Project description:Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.
| S-EPMC5275770 | biostudies-literature
Project description: Not available
| S-EPMC1797323 | biostudies-literature
Project description:Multiple sclerosis (MS) is a complex debilitating disease of the central nervous system (CNS) perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in CNS may result in neurological deficits. In this review article, we discuss the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in MS yet many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments.
| S-EPMC4249254 | biostudies-literature
Project description:Ovarian cancer is one of the most lethal gynecological cancers worldwide. The poor prognosis of this malignancy is substantially attributed to the inadequate symptomatic biomarkers for early diagnosis and effective remedies to cure the disease against chemoresistance and metastasis. Ovarian cancer metastasis is often relatively passive, and the single clusters of ovarian cancer cells detached from the primary ovarian tumor are transcoelomic spread by the peritoneal fluid throughout the peritoneum cavity and omentum. Our earlier studies revealed that lipid-enriched ascitic/omental microenvironment enforced metastatic ovarian cancer cells to undertake metabolic reprogramming and utilize free fatty acids as the main energy source for tumor progression and aggression. Intriguingly, cell susceptibility to ferroptosis has been tightly correlated with the dysregulated fatty acid metabolism (FAM), and enhanced iron uptake as the prominent features of ferroptosis are attributed to the strengthened lipid peroxidation and aberrant iron accumulation, suggesting that ferroptosis induction is a targetable vulnerability to prevent cancer metastasis. Therefore, the standpoints about tackling altered FAM in combination with ferroptosis initiation as a dual-targeted therapy against advanced ovarian cancer were highlighted herein. Furthermore, a discussion on the prospect and challenge of inducing ferroptosis as an innovative therapeutic approach for reversing remedial resistance in cancer interventions was included. It is hoped this proof-of-concept review will indicate appropriate directions for speeding up the translational application of ferroptosis-inducing compounds (FINs) to improve the efficacy of ovarian cancer treatment.
| S-EPMC9737695 | biostudies-literature