ABSTRACT
Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.
ABSTRACT
The application of immunotherapy has become a hot spot in tumor research currently. In particular, immune checkpoint inhibitors have played an important role in the treatment of advanced unresectable primary liver cancer. However, the efficacy of immune checkpoint inhibitors varies greatly in the treatment of different patients, which has aroused people's attention to the regulatory mechanism of PD-L1 in the immune escape of liver tumors. PD-L1 is regulated by multiple levels and multiple signaling pathways in liver cancer, including gene mutation, epigenetic mechanisms, transcriptional regulation, post-transcriptional regulation and post-translational modification. Studies have also found that the high expression of PD-L1 may be the main factor affecting the immunotherapy of primary liver cancer. Therefore, it can provide more evidence for immunotherapy and immune combination therapy strategies of primary liver cancer by clarifying the regulatory mechanism of PD-L1.
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Objective To investigate the effect of SABP, a water-soluble component of Salvia miltiorrhiza, on the growth of orthotopic transplantation of H22 liver cancer and the immune microenvironment of liver cancer. Methods We established a mouse model of orthotopic transplantation of H22 cell liver cancer in BALB/c mice. ELISA was used to detect the expression of PD-L1, TGF-β, IL-1β, IL-10, IL-4, IFN-γ, IL-18, IL-7, IL-2, CCL-2 and CCL-21 in the liver. We counted the organ indexes of liver, spleen and kidney. Results SABP inhibited the growth of orthotopic transplantation tumors of H22 cell liver cancer, and increased the expression levels of PD-L1, TGF-β, IL-1β and IL-10 in the microenvironment of liver cancer, as well as the liver, spleen and kidney coefficients. Conclusion SABP could inhibit the growth of orthotopic transplantation tumors of H22 cell liver cancer and promote the expression of PD-L1, TGF-β, IL-1β and IL-10 in the microenvironment of liver cancer.
ABSTRACT
Objective To study the characteristics of liver injury induced by simvastatin combined with HRZ (Isoniazid,Rifampicin and Pyrazinamide) in SD rats.Methods Fifty-four 8-week-old SD rats were randomly divided into 3 groups:group A (control),group B (HRZ) and group C (simvastatin combined to HRZ),half of each group were male.We calculated the accurate dose respectively before those rats were given intragastrical administration of corresponding drugs.Six rats were killed in each group on 10th,20th and 40th day,respectively.Before this,blood was fastened from femoral of every rat that would be killed to test liver function,liver tissue slices were made in order to observe the pathological characteristic.Results Alanine amiotransferase of group C elevated in line with time and reached statistic difference on 40th day,furthermore,it was significantly higher than group A (P＜0.05).Total bilirubin and direct Bilirubin of group C were significantly higher than those of group A from the beginning to the end (P＜0.05),however,they declined rapidly on 10th day,this trend also had statistic difference (P＜0.05) At the end of this experiment,hepatic cords was disordered slightly,but swelling liver cells and vacuolar degeneration were observed,the nuleus of cell condensed.Soakage of monocytes,neutrophils,and lymphocytes occurred in the portal and lobule regions,or even spotty necrosis occasionally.Conclusion Cholestasis occurs at the early stage when simvastatin is combined with HRZ in SD rats,however,it has a rapidly degressive trend.In contrast,Alanine amiotransferase elevates,furthermore,pathological injury or even spotty necrosis can emerge in liver tissue slices.