BackgroundThe current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver fibrosis. The aim was to investigate CO3-610 levels in another well characterised model of fibrosis, to better describe the biomarker in relation to additional fibrotic pathologies.MethodsSkin fibrosis was induced by daily injections of Bleomycin to a total of 52 female C3 H mice, while control mice (n = 28) were treated with phosphate buffered saline (PBS), for 2, 4, 6 or 8 weeks. Skin fibrosis was evaluated using Visiopharm software on Sirius-red stained skin sections. Urine ELISA assays and creatinine corrections were performed to measure CO3-610 levels.ResultsCO3-610 levels were significantly higher in Bleomycin-treated vs. PBS-treated mice at each time point of termination. The mean increases were: 59.2%, P < 0.0008, at 2 weeks; 113.5%, P < 0.001, at 4 weeks; 136.8%, P < 0.0001 at 6 weeks; 157.2%, P < 0.0001 at 8 weeks). PBS-treated mice showed a non-significant increase in CO3-610 levels (mean increase for weeks 2-8 = 1.7%, P = 0.789) CO3-610 levels assayed in urine were statistically significantly correlated with Western blot analysis showing increased skin fibrosis (P < 0.0001, r = 0.65).ConclusionIncreased levels in mouse urine of the MMP-9 mediated collagen III degradation fragment CO3-610 were correlated with skin fibrosis progression, suggesting that CO3-610 may be a potential positive biomarker to study the pathogenesis of skin fibrosis in mice.
New technologies are being developed toward the novel coronavirus SARS-CoV-2 to understand its pathogenesis and transmission, to develop therapeutics and vaccines, and to formulate preventive strategies. Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies. Importantly, applications of traditional mice and rat models are limited for studying SARS-CoV-2 and development of COVID-19. Non-human primates, Syrian hamsters, ferrets, cats, and engineered chimeras mimic the human infection more closely and hold strong potential as animal models of SARS-CoV-2 infection and progression of resulting human disease.
The herb Evolvulus nummularius (L). L generally grown as an ornamental plant has found many applications in traditional folk medicine. There was however insufficient scientific data to back its safety to be used on humans. Methanolic extract of E. nummularius was used to check for its safety as a vaginal microbicide through various safety tests such as cell viability using MTT assay on three female genital tract epithelial cell lines, vaginal (VK2/E6E7), endocervical (End1/E6E7) and endometrial (HEC-1-A). Quantification of hemolytic activity was done on human red blood cells (RBCs). Determination of cellular integrity was checked by transepithelial electrical resistance (TER) assay and permeability by fluorescent microsphere assay. At 24 hours, application of the extract for cell viability assay showed extensive cell death with cell disruption. IC 50 of VK2/E6E7 and HEC-1-A cells were found to be 2 mg/ml, IC 50 of End1/E6E7 was 1 mg/ml. For hemolytic assay, with treatment of the extract for one hour did not show hemolysis till the concentration of 2.5mg/ml. In TER and microsphere permeability assays, polarized HEC-1-A monolayer 24 hours post treatment had significant drop in TER and enhanced fluorescence from passage of microspheres implying disruption of the epithelial monolayer. The study revealed that the crude methanolic extract appeared to be toxic towards human RBCs and female genital tract epithelial cells. Due to its toxic nature, its direct applications to the human vaginal tissue in vivo should be done with caution.
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