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IL-12 is a cytokine which showed anti-tumor effects in clinical trials, but also produced serious toxicity. We describe a fusion protein, huBC1-IL12, designed to achieve an improved therapeutic index by specifically targeting IL-12 to tumor and tumor vasculature. huBC-1 is a humanized antibody that targets a cryptic sequence of the human ED-B-containing fibronectin isoform, B-FN, present in the subendothelial extracellular matrix of most aggressive tumors. B-FN is oncofetal and angiogenesis-associated, and is undetectable in most normal adult tissues. The original murine BC-1 antibody has been used successfully for immunoscintigraphy to image brain tumor mass in glioblastoma patients. In huBC1-IL12, each of the IgG heavy chains is genetically fused to the N-terminus of the IL-12 p35 subunit, which in turn is disulfide-bonded to the p40 subunit, resulting in a hexameric molecule of MW of approximately 300 kDa. Since human IL-12 has no biological activity in mice, we produced huBC1-muIL12 as a surrogate molecule for animal tumor models. Despite the relatively poor PK profile of this molecule in mice and the apparent drawbacks of xenogeneic models in SCID mice, which lack T and B cells, one cycle of treatment with huBC1-muIL12 was efficacious in the PC3mm2, A431, and HT29 subcutaneous tumor models and PC3mm2 lung metastasis model. This molecule also was found to have surprisingly low toxicity in immunocompetent mice. A fusion protein that contains human IL-12 (huBC1-huIL12), which is a suitable molecule for investigation as a therapeutic, has also been produced. This protein has been shown to have a longer serum half-life than huBC1-muIL12 in mice, and retains both antigen binding and IL-12 activity in in vitro assays.

Coronaviruses are single stranded RNA viruses usually present in bats (reservoir hosts), and are generally lethal, highly transmissible, and pathogenic viruses causing sever morbidity and mortality rates in human. Several animals including civets, camels, etc. have been identified as intermediate hosts enabling effective recombination of these viruses to emerge as new virulent and pathogenic strains. Among the seven known human coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 (2019-nCoV) have evolved as severe pathogenic forms infecting the human respiratory tract. About 8096 cases and 774 deaths were reported worldwide with the SARS-CoV infection during year 2002; 2229 cases and 791 deaths were reported for the MERS-CoV that emerged during 2012. Recently ~ 33,849,737 cases and 1,012,742 deaths (data as on 30 Sep 2020) were reported from the recent evolver SARS-CoV-2 infection. Studies on epidemiology and pathogenicity have shown that the viral spread was potentially caused by the contact route especially through the droplets, aerosols, and contaminated fomites. Genomic studies have confirmed the role of the viral spike protein in virulence and pathogenicity. They target the respiratory tract of the human causing severe progressive pneumonia affecting other organs like central nervous system in case of SARS-CoV, severe renal failure in MERS-CoV, and multi-organ failure in SARS-CoV-2. Herein, with respect to current awareness and role of coronaviruses in global public health, we review the various factors involving the origin, evolution, and transmission including the genetic variations observed, epidemiology, and pathogenicity of the three potential coronaviruses variants SARS-CoV, MERS-CoV, and 2019-nCoV. Electronic supplementary material The online version of this article (10.1007/s13337-020-00632-9) contains supplementary material, which is available to authorized users.

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BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF‐kB/COX‐2) and apoptosis (caspase‐3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative load as evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf‐2/HO‐1, SIRT‐1/FOXO‐1 and reduced inflammatory proteins NF‐kB/COX‐2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl‐2), gap junction (connexin‐43) and decreased apoptosis (caspase‐3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus.