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Cancer has remained the second leading cause of death globally (≈9.95 million in 2020).Over the past few years, using the scorpion venom peptides in diagnosing cancer has led a growing number of studies on exploring anticancer properties of different species of scorpion venoms. In this study, anticancer property of Hottentotta rugiscutis (H.rugiscutis) venom against breast (MCF-7) and oral (KB3-1) cancer cell lines has been evaluated. Cytotoxicity of H.rugiscutis venom was determined by MTT assay. Cell cycle and caspase 9 expressions was analysed by flow cytometry. Effect of H.rugiscutis venom on cell proliferation was studied by wound healing assay. H.rugiscutis venom showed significant cytotoxic activity with the IC 50 values of 279 µg/ml and 373 µg/ml on MCF-7 and KB3-1 cell lines respectively. H.rugiscutis venom induced caspase-9 expression in both cell lines. Cell cycle analysis showed that H.rugiscutis venom arrested the cells at Sub G0 /G1 phase of cell cycle of KB3-1 and MCF-7 cell lines. Further, cell proliferation (wound healing) assay showed H.rugiscutis venom inhibited 18% and 13 % of cell migration of MCF-7and KB3-1cell respectively. These cumulative results confirm the action of H.rugiscutis venom in induction of apoptosis in breast and oral cancer cell lines.

The scorpions of the Buthidae family exhibit diverse toxins with proven pharmacological activities and yet underexplored. The Hottentotta rugiscutis is a commonly found south-Indian buthid scorpion, whose venom proteomic profile is unknown. In this study, the venom was biochemically and immunologically characterized by SDS-PAGE, MALDI-TOF MS, western blot and ELISA. The regional and seasonal variation in the venom composition from the same species was also assessed at the molecular mass level. The venom was further studied in albino mice to understand its impact on various blood parameters. The venom has varied MW proteins between 6-275 kDa, four of them were found to be major immunodominant proteins. The mass spectra have revealed that some proteins are predominantly present in the venom of 3–4.5 kDa or 6.5–8.0 kDa, which could be the K+ or Na+ channel blockers respectively whose ratio varied by season. The obtained venom-mass spectra could also be used as H. rugiscutis specific finger-print in identifying the region-specific species. The venom was found to elicit a stress-induced innate immune response in mice, giving rise to a strong Th2 mediated humoral immune response. Overall, this study has provided a glimpse of the venom composition and its immunogenicity.

The Ebola virus (EBOV), responsible for causing severe Ebola virus disease (EVD) mostly in West Africa, is characterized by the sudden onset of hemorrhagic fever leading to severe complications. The EVD has become a global health concern because of its severity, mortality, rapid dissemination, and repeated outbreaks. EVD outbreaks typically begin with a single case of zoonotic transmission, followed by human-to-human transmission via direct contact or with infected bodily fluids. Mechanistically, the EBOV initially infects the macrophages and dendritic cells followed by other body cells. The initial innate immune response is characterized by a cytokine storm, with the secretion of numerous pro-inflammatory cytokines, leading to the induction of a huge number of contradictory signals in immune cells and other tissues causing deleterious effects. The disease virulence can be attributed to several immunoevasion mechanisms such as early inhibition of innate immunity by the downregulation of interferon, epitope masking, and subversion of the adaptive humoral immunity by secreting a truncated form of the viral glycoprotein. The compromised specific and nonspecific antiviral response results in an unrestricted viral replication and dissemination in the host, causing death, typically within 10 days after the onset of symptoms. Herein, we have discussed the molecular basis of EVD pathogenesis with a focus on the dysregulation of innate and adaptive immune response signaling pathways, clinical manifestations, development of vaccine and therapeutics, along with long-term health sequelae for EVD survivors.

The Hottentotta rugiscutis scorpion venom (Hrv) contains neurotoxins, which elicit a strong innate immune response through the activation of the Hypothalamus-pituitary-adrenal axis, which could improve the quality of adaptive immunity. Hence, the Hrv was used as an adjuvant for the Hepatitis-B virus surface antigen (HBsAg) and assessed its ability in the activation of innate (NGF, CORT, cellularity, NO) and adaptive (IgM, IgG, IgG1/IgG2a/IgG2b/IgG3, Th1/Th2 cytokines, avidity) immunity. Here, the Hrv and HBsAg were given in the mixed form (HBsAg-Hrv) as well as in a separate form (HBsAg+Hrv). The NGF levels in plasma/spleen and CORT in plasma were found to be elevated optimally at 5 h and 6 h post-Hrv injection, respectively. Further studies showed that CORT and NGF levels were also highly upregulated in the HBsAg-Hrv group. The HBsAg-specific IgM titer was found to be increased in the HBsAg+Hrv group and total IgG was relatively similar among alum and Hrv-test groups, but IgG2a/IgG2b/IgG3 levels were higher along with IL-1β in HBsAg-Hrv groups. The study showed that the venom from H. rugiscutis acts as a vaccine adjuvant for HBsAg to develop strong antigen-specific Th1 immunity. The Hrv also enhances the antibody-avidity which may improve the neutralizing ability of antibodies with systemic infectious agents. The study also elucidated that the venom acts by neuroendocrine-immune mechanism and majorly impacts splenocytes through NGF and corticosterone.

Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of death in children under the age of five in developing countries. ETEC (O78:H11:CFA/I:LT+:ST+) mechanism has been studied in detail with either heat labile (LT) or heat stable (ST) toxins using in vitro and in vivo models. However, there is no adequate information on ETEC pathogenesis producing both the toxins (LT, ST) in BALB/c mice model. In this study, female mice have been employed to understand ETEC H10407 infection induced changes in physiology, biochemical and immunological patterns up to seven days post-infection and the antidiarrhoeal effect of Simarouba amara (Aubl.) bark aqueous extract (SAAE) has also been looked into. The results indicate that BALB/c is sensitive to ETEC infection resulting in altered jejunum and ileum histomorphology. Withal, ETEC influenced cAMP, PGE2, and NO production resulting in fluid accumulation with varied Na+, K+, Cl-, and Ca2+ levels. Meanwhile, ETEC subverted expression of IL-1β, intestine alkaline phosphatase (IAP), and myeloperoxidase (MPO) in jejunum and ileum. Our data also indicate the severity of pathogenesis reduction which might be due to attainment of equilibrium after reaching optimum rate of infection. Nevertheless, degree of pathogenesis was highly significant (p < 0.01) in all the studied parameters. Besides that, SAAE was successful in reducing the infectious diarrhoea by inhibiting ETEC H10407 in intestine (jejunum and ileum), and shedding in feces. SAAE decreased cAMP, PGE2, and fluid accumulation effectively and boosted the functional activity of immune system in jejunum and ileum IAP, MPO, IL-1β, and nitric oxide.