BackgroundMore than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay.Methodology/Principal FindingsμCT and 18F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis.Conclusions/SignificanceThe present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.Main methods: Eighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically.The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR. Key findings: Administration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues.Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4. Significance: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

Summary Due to the Covid‐19 pandemic caused by SARS‐CoV‐2, transplant programs worldwide have been severely impacted with dwindling numbers of transplantations performed and a complete halt in several areas. In this review we examine whether SARS‐CoV‐2 infection presents differently in transplant recipients, whom and how we should test, how susceptible the transplant population is to overt infection and describe the range of outcomes. From retrieved published reports on SARS‐CoV‐2infections in 389solid organ transplant recipients reported in the literature, the overall mortality rate was 16.7% ( n = 65); however for those with mild or moderate Covid‐19 disease this was 2.9% and 2.3% respectively; conversely, for those with severe infection the mortality rate was 52.2%.We then address questions regarding halting transplantation programs during this pandemic, whether all human tissues being considered for transplantation are capable of transmitting the infection, and if we should alter immunosuppressive medications during the pandemic.

Objectives: To identify the regulated genes or the spliced genes of diethylnitorsamine (NDEA) in ATT-myc mice versus control group. Methods: We analysed the 9 hybridizations on the MouseExon10ST array of NDEA treatments and control non- transgenic by application of a mixed model analysis of variance. Results: The 907 genes had regulated significantly between the groups and 916 genes had regulated with a significant exon-group interaction among of them 150 genes had regulated with both gene and possible splicing differences (p<0.01). The 7,618 genes had tested for the alternative gene up-regulation and splicing and compared to the gene-classifications. The genes functions, pathways and gene-classifications in the current study had presented in the contingency table analysis of the set of the regulated genes and alternatively spliced that regulated significantly in the ATT-myc mice treated by diethylnitorsamine versus control non-transgenic. The GOMolFn of gene-classification had 321 groups that had significantly regulated in the set of the regulated genes or differentially spliced. While the GOProcess of gene-classification had 330 groups that had significantly regulated in the set of differentially regulated genes or spliced. Additionally, the CELlLoc of gene-classification had 70 groups that had significantly regulated in the set of differentially regulated genes spliced. Finally, the Pathway gene-classification had 8 groups that had significantly regulated in the set of differentially regulated genes or spliced (p<0.01) in diethylnitorsamine when compared to control group. Conclusion: we summarized the toxicogenomics induced by diethylnitrosamine in early liver carcinogenesis in ATT-myc transgenic mice of liver cancer. Doi: 10.28991/SciMedJ-2021-0302-6 Full Text: PDF