Protective activities of ellagic acid and urolithins against kidney toxicity of environmental pollutants: A review

Oxidative stress and inflammation are two possible mechanisms related to nephrotoxicity caused by environmental pollutants. Ellagic acid, a powerful antioxidant phytochemical, may have great relevance in mitigating pollutant-induced nephrotoxicity and preventing the progression of kidney disease. This review discusses the latest findings on the protective effects of ellagic acid, its metabolic derivatives, the urolithins, against kidney toxicity caused by heavy metals, pesticides, mycotoxins, and organic air pollutants. We describe the chelating, antioxidant, anti-inflammatory, antifibrotic, antiautophagic, and antiapoptotic properties of ellagic acid to attenuate nephrotoxicity. Furthermore, we present the molecular targets and signaling pathways that are regulated by these antioxidants, and suggest some others that should be explored. Nevertheless, the number of reports is still limited to establish the efficacy of ellagic acid against kidney damage induced by environmental pollutants. Therefore, additional preclinical studies on this topic are required, as well as the development of well-designed clinical trials.     

Quantitative Assessment and Predicting the Effects of Soil Pollutants on Herbaceous Biomass Production in Reserved Forests

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Heavy metal concentrations in surface soils of Reserved Forests (RFs) have a significant impact on...     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.     

Longistylin A,a natural stilbene isolated from the leaves of Cajanus cajan,exhibits significant anti-MRSA activity

Longistylin A (LLA) is an abundant stilbene isolated from the leaves of Cajanus cajan (L.) Millsp. However, the antibacterial effect of LLA is not yet understood. Therefore, in this study, a detailed investigation of the antibacterial effect of LLA, particularly against methicillin-resistant Staphylococcus aureus (MRSA), was conducted. In vitro, LLA exhibited strong antibacterial activity against MRSA with a minimum inhibitory concentration (MIC) of 1.56 µg/mL and displayed much more rapid bactericidal activity (3-log decrease in MRSA survival within 8 h) than vancomycin. A membrane-targeting experiment suggested that the antibacterial activity of LLA is associated with perturbation of the bacterial membrane potential and increased membrane permeability. Notably, LLA had relatively weak cytotoxicity to murine macrophages [50% cytotoxic concentration (CC₅₀) = 8.61 ± 0.57 µg/mL]. In vivo, topical treatment of a skin injury with LLA improved wound healing and closure in an MRSA-infected wound healing mouse model. After 3 days treatment, LLA decreased MRSA bacterial counts in the wounded region, reduced the accumulation of immune cells at the injury site, and alleviated induction of the inflammatory cytokines tumour necrosis factor-alpha (180.74 ± 10.78 pg/mL vs. 606.57 ± 68.99 pg/mL) and interleukin-6 (87.25 ± 10.19 pg/mL vs. 280.58 ± 42.27 pg/mL) in serum.     

Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.     

Identification of B cell epitopes of Per a 5 allergen using bioinformatic approach

BackgroundImmune epitopes of allergens are pivotal for development of novel diagnostic and therapeutic modalities. Present study aims to identify antigenic determinants of Per a 5, a clinically relevant cross reactive cockroach allergen.MethodsThe three dimensional structure of Per a 5 was modelled using Modeller 9v11 software. A combination of sequence and structure based computational tools were employed for predicting B cell epitopes. Epitopes were synthesized and immunoreactivity was assessed by ELISA using cockroach hypersensitive patient’s sera. Cross-reactivity potential of predicted epitopes was assessed with SDAP and ConSurf and validated by IgE ELISA with fungal and mite hypersensitive patient’s sera.ResultsPer a 5 structure exhibited good quality factor in ERRAT and high stereochemical stability. In silico analysis revealed six B cell epitopes (BC-P1 to P6). BC-P3 demonstrated significant IgE binding followed by BC-P2 and BC-P1 with cockroach hypersensitive patient’s sera. Per a 5 epitopes demonstrate considerable similarity with broad spectrum of allergens from fungal, mites, helminths, fruits and nuts. Analysis of PD values indicate BC-P4 to be well conserved among dust mite and helminth GSTs (8.89, 10.63 and 10.69 with D. pteronyssinus, W. bancrofti and F. hepatica respectively). ConSurf analysis of Per a 5 revealed specific enrichment of evolutionarily similar amino acid residues in BC-P2 (with fungal and mite GSTs) and BC-P4 (with mite and helminth GSTs). Further, IgE binding analysis of epitopes demonstrate BC-P2, BC-P3 and BC-P5 as high IgE binders in fungal hypersensitive sera while BC-P1, BC-P2, BC-P4 and BC-P5 demonstrated significant IgE binding with mite hypersensitive sera.ConclusionsAmong the predicted epitopes, BC-P3 demonstrates maximal IgE binding ability. Computational analysis suggests strong evolutionary conservation and cross reactive potential of BC-P4 with allergens in dust mite and helminths. ELISA highlights predictive potential of analysing evolutionarily conserved residues for uncovering potentially cross reactive antigenic determinants.General significanceImmune epitopes of Per a 5 were identified for aiding molecular diagnosis and potential cross reactivity.     

Genotoxic effect of smoke-dried meat extract in Swiss albino mice using sperm head shape abnormality test.

The genotoxic effect of an extract of smoke-dried meat was assayed by employing in vivo sperm head shape abnormality. A significant dose responsive mutagenic effect was observed using the sperm head shape abnormality test. The result indicates that higher doses i.e., 100 and 200 mg/kg body wt. of smoke meat extract, significantly induced sperm head shape abnormality as compared to lower doses i.e., 20 mg/kg body wt. and control.