Recent advances in the metabolomic study of bladder cancer

Introduction: Metabolomics is a chemical process, involving the characterization of metabolites and cellular metabolism. Recent studies indicate that numerous metabolic pathways are altered in bladder cancer (BLCA), providing potential targets for improved detection and possible therapeutic intervention. We review recent advances in metabolomics related to BLCA and identify various metabolites that may serve as potential biomarkers for BLCA.

Areas covered: In this review, we describe the latest advances in defining the BLCA metabolome and discuss the possible clinical utility of metabolic alterations in BLCA tissues, serum, and urine. In addition, we focus on the metabolic alterations associated with tobacco smoke and racial disparity in BLCA.

Expert commentary: Metabolomics is a powerful tool which can shed new light on BLCA development and behavior. Key metabolites may serve as possible markers of BLCA. However, prospective validation will be needed to incorporate these markers into clinical care.     

The 29-kilodalton thiol-dependent peroxidase of Entamoeba histolytica is a factor involved in pathogenesis and survival of the parasite during oxidative stress

The 29-kDa surface antigen (thiol-dependent peroxidase; Eh29) of Entamoeba histolytica exhibits peroxidative and protective antioxidant activities. During tissue invasion, the trophozoites are exposed to oxidative stress and need to deal with highly toxic reactive oxygen species (ROS). In this investigation, attempts have been made to understand the role of the 29-kDa peroxidase gene in parasite survival and pathogenesis. Inhibition of eh29 gene expression by antisense RNA technology has shown approximately 55% inhibition in eh29 expression, maximum ROS accumulation, and significantly lower viability in 29-kDa downregulated trophozoites during oxidative stress. The cytopathic and cytotoxic activities were also found to decrease effectively in the 29-kDa downregulated trophozoites. Size of liver abscesses was substantially lower in hamsters inoculated with 29-kDa downregulated trophozoites compared to the normal HM1:IMSS. These findings clearly suggest that the 29-kDa protein of E. histolytica has a role in both survival of trophozoites in the presence of ROS and pathogenesis of amoebiasis.     

Length–weight relationships of some fish from the Ganga River,India

Length–weight relationships (LWRs) were determined for seven riverine fish species from the river Ganga, India. Specimens were collected on a bi‐monthly basis from April 2017 to December 2018 using gill nets (mesh size 22–34 mm), cast nets (mesh size 16 mm) and bag nets (mesh size 14–22 mm). Total length was measured to the nearest 0.1 cm using a digital caliper and weight was recorded to the nearest 0.01 g on an electronic balance. From estimated length–weight relationships, the values for parameter “a” ranged from 0.004 (Bregmaceros mcclellandi and Setipinna tenuifilis) to 0.014 (Brachirus pan). Likewise, the values for the parameter “b” of the equation ranged from 2.958 (Bagarius bagarius) to 3.124 (Bregmaceros mcclellandi) and r² from 0.978 (Gonialosa manmina) to 0.996 (Brachirus pan).     

Lipoxygenase inhibitor from Lactobacillus casei

An inhibitor of plant lipoxygenase from culture filtrates of Lactobacillus casei was purified by column chromatography and shown to be benzoic acid. The isolated benzoic acid had an IC₅₀ of 350 M against purified soybean lipoxygenase at pH 9. L. casei therefore may have the potential to be used as a preservative against the oxidation of unsaturated fatty acids, thereby preventing undesirable flavours in foods.     

Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester

Thalidomide ([+]-alpha-phthalimidoglutarimide), a psychoactive drug that readily crosses the blood-brain barrier, has been shown to exhibit anti-inflammatory, antiangiogenic, and immunosuppressive properties through a mechanism that is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that thalidomide mediates its effects through suppression of NF-kappaB activation. We investigated the effects of thalidomide on NF-kappaB activation induced by various inflammatory agents in Jurkat cells. The treatment of these cells with thalidomide suppressed TNF-induced NF-kappaB activation, with optimum effect occurring at 50 microg/ml thalidomide. These effects were not restricted to T cells, as other hematopoietic and epithelial cell types were also inhibited. Thalidomide suppressed H(2)O(2)-induced NF-kappaB activation but had no effect on NF-kappaB activation induced by PMA, LPS, okadaic acid, or ceramide, suggesting selectivity in suppression of NF-kappaB. The suppression of TNF-induced NF-kappaB activation by thalidomide correlated with partial inhibition of TNF-induced degradation of an inhibitory subunit of NF-kappaB (IkappaBalpha), abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Thalidomide abolished the NF-kappaB-dependent reporter gene expression activated by overexpression of TNFR1, TNFR-associated factor-2, and NF-kappaB-inducing kinase, but not that activated by the p65 subunit of NF-kappaB. Overall, our results clearly demonstrate that thalidomide suppresses NF-kappaB activation specifically induced by TNF and H(2)O(2) and that this may contribute to its role in suppression of proliferation, inflammation, angiogenesis, and the immune system.     

Inhibition of the 26S proteasome induces expression of GLCLC, the catalytic subunit for gamma-glutamylcysteine synthetase

The majority of short- and long-lived cellular proteins are degraded by the activities of the 26S proteasome, a large multi-catalytic protease. Its unique function places it as a central regulatory activity for many important physiological processes. Lactacystin is a very specific 26S proteasome inhibitor and represents an excellent tool for demonstrating that a pathway exhibits proteasome-dependent biochemical regulation. Exposure of HepG2 cells to lactacystin resulted in robust elevation of GLCLC mRNA levels, followed by an increase in GSH concentrations. GLCLC is the gene that encodes the catalytic subunit for gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the synthesis of glutathione (GSH). Inhibition of non-proteasome, protease activities did not induce GLCLC. Gel mobility shift assays and expression of CAT activity from heterologous reporter vectors identified Nrf2 mediation of the GLCLC antioxidant response element, ARE4, as the mechanism by which lactacystin induced GLCLC. These studies have identified 26S proteasome activity as a central regulatory pathway for glutathione synthesis.     

Molecular characterization and expression analysis of BmNOX in two strains of Bombyx mori with contrasting viral resistance phenotype

We recently documented the identification of a 26.5 kDa protein named BmNox in the gut fluid of Nistari strain of Bombyx mori, which possessed antiviral activity against BmNPV in vitro. In this report, we report the characterization of the full‐length gene encoding BmNOX and the levels of expression of this gene in select tissues of silkworm larvae from a BmNPV‐susceptible and a BmNPV‐resistant strain to the defense capability in Bombyx mori larvae challenged with BmNPV. We also evaluated the BmNox expression in various stages of larval life of a resistant and a susceptible strain of Bombyx mori selected from among a panel of strains of silkworm. Nistari, a multivoltine strain of silkworm, expressed BmNOX during all five larval stages, and were highly resistant to BmNPV infection. In sharp contrast, CSR₂, a bivoltine strain, showed weaker expression of BmNOX in the anterior midgut in larval life and was highly susceptible to BmNPV infection. BmNOX is a secretory protein with dual expression in gut fluid and mid gut tissue. BmNOX is expressed heavily in the posterior mid gut, with weaker expression in the fore‐ and mid‐gut regions. © 2010 Wiley Periodicals, Inc.