ABSTRACT
Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg-1·d-1, i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration.
Subject(s)
Hepatocytes , PPAR alpha , Animals , Mice , Cell Proliferation , Hepatocytes/metabolism , Hepatomegaly/chemically induced , Hepatomegaly/metabolism , Hypertrophy/chemically induced , Hypertrophy/metabolism , Liver/metabolism , Mice, Knockout , PPAR alpha/agonistsABSTRACT
@#navirus disease 2019 (COVID-19) in the patients younger than 18 years old infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and to provide a basis for determining the chest CT changes and efficacy of COVID-19 caused by Omicron virus variant in patients younger than 18 years old. Methods The clinical and imaging data of 30 cases of patients younger than 18 years old infected with COVID-19 Omicron variant, who admitted to the Third People's Hospital of Shenzhen from February 11 to March 26, 2022 were collected and retrospectively analyzed. The clinical manifestations, imaging features and dynamic changes of lesions were summarized. Results A total of 41 intrapulmonary lesions in 30 patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The main manifestations were patchy or nodular ground-glass opacities and/or consolidation, with focal subpleural distribution, lesions mainly occur in the right lung (70.73%, 29/41). There were 42 lesion morphologies, with 22 (52.38%) striped shadows and 16 (38.10%) nodular shadows, with small lamellar and patchy shadows predominating. There were 36 lesion density variations, with ground glass shadows being the most common, with a total of 24 ground glass shadows (66.66%) in each lobe of the lung, and also 6 consolidation lesions (16.67%) and 6 mixed ground glass opacity and consolidation lesions (16.67%). With the progression of the disease, lesions gradually enlarged, appeared on the 2nd day (312.93 mm3), peaked on the 9th day (1 837.18 mm3). The average absorption time of the lesions was (16±3) days, and there was no significant difference between the absorption time of patchy and nodular lesions (ground glass and/or consolidation) (t=0.853, P>0.05). The lesions showed focal ground-glass opacity in the early stage, 77.78% lesions were absorbed after treatment in the late stage. Inflammatory nodules were absorbed slowly (9-19 days), without residual fibrotic changes. Conclusions The imaging manifestations of COVID-19 in patients younger than 18 years old infected with SARS-CoV-2 Omicron variant have certain characteristics, showed patchy or nodular ground glass opacities and/or consolidation, mainly distributed in the subpleural area, with small and few lesions and slow change, didn't remain fibrosis. Being familiar with its clinical and imaging manifestations can assist in early diagnosis, but confirming the diagnosis requires a combination of epidemiological history, clinical symptoms, SARS-CoV-2 nucleic acid and radiological manifestations.
ABSTRACT
@#Abstract: Objective To analyze the clinical characteristics and changes of serum IgG, IgM antibodies in patients infected with the SARS-CoV-2 B.1.1.529 (Omicron) variant. Methods The clinical data of 82 patients with SARS-CoV-2 B.1.1.529 variant was analyzed retrospectively. Based on the presence of pneumonia on chest CT, the patients were divided into pneumonia group and non-pneumonia group. Serum IgG, IgM antibodies were observed at 5 time points T1 (1~<4 d), T2 (4~<8 d), T3 (8~<15 d), T4 (15~<22 d) and T5 (22~<30 d) after admission. Results Among the 82 patients infected with the SARS-CoV-2 B.1.1.529 variant strain, there were 62 cases of cough, 31 cases of fever, 33 cases of throat discomfort, 5 cases of muscle soreness and 3 cases of diarrhea. The serum IgG antibody levels at 5 time points were 50.22 (142.20) AU/mL, 326.50 (220.63) AU/mL, 368.23 (76.21) AU/mL, 368.65 (79) AU/mL, and 385.26 (113.10) AU/mL, respectively. The level of serum IgG antibody in the pneumonia group was lower than that of the non-pneumonia group at T1 and T4 time points, and the differences were statistically significant (P<0.05) , the positive rate of serum IgG antibody in the pneumonia group was lower than that of the non-pneumonia group at the T1 time point, and the difference was statistically significant (P<0.05) . The serum IgM antibody levels at 5 time points were 0.41 (0.81) AU/mL, 0.95 (1.62) AU/mL, 1.09 (2.42) AU/mL, 0.74 (3) AU/mL, and 0.81 (3.10) AU/mL respectively, and there was no significant difference between the two groups. Conclusion The clinical symptoms of patients infected with the SARS-CoV-2 B.1.1.529 variant strain are mild. Serum IgG antibodies increased after infection, but there are some differences between the pneumonia group and the non-pneumonia group, whether serum IgG has a protective effect needs further research; the serum IgM antibodies do not increase highly after infection, there are some differences between individuals.
ABSTRACT
BACKGROUND: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown. PURPOSE: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly. METHODS: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence. RESULTS: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice. CONCLUSION: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.
