To research the effect of Jianpi Jiedu decoction (JPJDT) to PTEN/ERK1 of athymic mice with hepatocellular carcinoma.N2 male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 90 athymic mice were distributed randomly into JPJDT groups: A, B, C, D, E, F, G, NS, FT each group had 10 athymic mice. Another 10 male BALB/c athymic mice without HCC was treated by NS as normal control (DZ). Group A to G were treated by intragastric administration with JPJDT that had been deliquated into 7 kinds of density for 8 wk. Group NS were were treated by intragastric administration with Sodium Chloride for 8 wk. Group FT were were treated by intragastric administration with FT207 (tegafur) for 8 wk . At last, athymic mice were sacrificed. PTEN/ERK1 was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry (PowerVision two-step histostaining reagent).The expression intensity of PTEN: The result showed that the intensity of PTEN in the normal hepatic tissue was the highest, and then latero-cancer tissue, the lowest was cancer tissue. In the normal hepatic tissue, the intensity of PTEN in Group B, D, E was higher than the Group NS, Group FT, Group DZ (P < 0.05). In the latero-cancer tissue, the intensity of PTEN in Group D was higher than the Group NS (P < 0.05). In the cancer tissue, the intensity of PTEN in Group JPJDT was higher than the Group NS and Group FT (P < 0.05). The expression intensity of ERK1: The result showed that the intensity of PTEN in the cancer tissue was the highest, and then latero-cancer tissue, the lowest was normal hepatic tissue. In the latero-cancer tissue, the intensity of ERK1 in Group FT was higher than the Group NS and Group JPJDT (P < 0.05). In the cancer tissue, the intensity of PTEN in Group NS and Group FT was higher than the Group C, D, E, G, F (P < 0.05). The correlation between PTEN and ERK1: The result showed that there was inverse correlation between the expression intensity of PTEN and ERK1 in the cancer tissue (P < 0.01).One of mechanism of antitumous effect of JPJDT maybe up-regulate anti-oncogene PTEN, restrain the signal way of ERK1, suppress the proliferation of hepatoma carcinoma cell. The carcinogenesis of primary hepatic carcinoma may exist the deletion of PTEN. Owing to low expression or deletion of PTEN in the cancer tissue, ERK1 signal transduction pathway cannot be actively suppressed which was activated by carcinogenic factor. So hepatoma carcinoma cell multiplicated.
Background: Hepatocellular Carcinoma (HCC) is a common lethal digestive system tumor. The oxidative stress mechanism is crucial in the HCC genesis and progression. Methods: Our study analyzed single-cell and bulk sequencing data to compare the microenvironment of non-tumor liver tissues and HCC tissues. Through these analyses, we aimed to investigate the effect of oxidative stress on cells in the HCC microenvironment and identify critical oxidative stress response-related genes that impact the survival of HCC patients. Results: Our results showed increased oxidative stress in HCC tissue compared to non-tumor tissue. Immune cells in the HCC microenvironment exhibited higher oxidative detoxification capacity, and oxidative stress-induced cell death of dendritic cells was attenuated. HCC cells demonstrated enhanced communication with immune cells through the MIF pathway in a highly oxidative hepatoma microenvironment. Meanwhile, using machine learning and Cox regression screening, we identified PRDX1 as a predictor of early occurrence and prognosis in patients with HCC. The expression level of PRDX1 in HCC was related to dysregulated ribosome biogenesis and positively correlated with the expression of immunological checkpoints (PDCD1LG2, CTLA4, TIGIT, LAIR1). High PRDX1 expression in HCC patients correlated with better sensitivity to immunotherapy agents such as sorafenib, IGF-1R inhibitor, and JAK inhibitor. Conclusion: In conclusion, our study unveiled variations in oxidative stress levels between non-tumor liver and HCC tissues. And we identified oxidative stress gene markers associated with hepatocarcinogenesis development, offering novel insights into the oxidative stress response mechanism in HCC.
To research the treatment effect of complex prescription of Chinese crude drug in BALB/c athymic mice with human liver cancer, which were built by Bel-7402.48 male BALB/c athymic mouse models were built by Bel-7402 with an indirect method. After 24 hours of postoperation, the 48 athymic mice were distributed randomly into 4 groups which were treated by intragastric administration with complex prescription of Chinese crude drug that had been deliquated into 3 groups by the different density as the low, middle, and high and FT207 (Tegafur) for 4 weeks. At last, athymic mice were put to death and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry (PowerVision Two-Step Histostaining Reagent).All of the 48 athymic mice survived 12 to 28 days (Ms 24 days) and every mouse with liver cancer demonstrated by dissection. The result of immunohistochemistry represents that the intensity of PTEN in latero-cancer tissue is the highest, and then the hepatic tissue, the lowest is cancer tissue, P < 0.01. It also represents that the intensity of PTEN in treatment groups (A, B, C) is more higher than the control group (D), P < 0.05 or P < 0.01, and group B is the highest in the treatment groups, P < 0.05 or P < 0.01. However, there is no significant statistic difference between group A and group C.The higher expression of PTEN in the laterocancer tissue can represent the protective reaction of stress of the organism. And anticancer effect of this complex prescription of Chinese crude drug relates to an eligible density of it. Mechanisms of this complex prescription of Chinese crude drug healing HCC may partially be explained by enhancing the expression of PTEN in liver.
Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene–environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10–26 and 1.41 × 10–9 for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10−5). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10−10), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10−8 for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.
Abstract Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy. It has been reported that serglycin is a novel ligand for the stem cell marker CD44. Interestingly, we found a positive correlation between serglycin expression and CD44 in nasopharyngeal tissues and NPC cell lines. Further study revealed that CD44 was an ERK-dependent downstream effector of serglycin signaling, and serglycin activated the MAPK/ β -catenin axis to induce CD44 receptor expression in a positive feedback loop. Taken together, our novel findings suggest that ECM serglycin upregulated CD44 receptor expression to maintain NPC stemness by interacting with CD44 and activating the MAPK/ β -catenin pathway, resulting in NPC cell chemoresistance. These findings suggest that the intervention of serglycin/CD44 axis and downstream signaling pathway is a rational strategy for targeting NPC cancer stem cell therapy.
To examine the expression of IL-1beta, IL-1ra and IL-1R mRNA in the dentate gyrus of adult rats after lithium-pilocarpine (Li-PILO)-induced seizures.Seizure epilepticus (SE) was induced using Li-PILO intraperitoneally (i.p.) injection. Lithium chloride was injected 18-20 h prior to PILO. The rats in the control group were given physiological saline instead of pilocarpine. We observed the behavior of rats and examined the expression of cytokines mRNA in dentate gyrus by RT-PCR.Rats had seizure epilepticus in 30 min after administrated of pilocarpine. Cytokines (IL-1beta, IL-1ra and IL-1R) began to increase significantly (P<0.05) at 1 h after SE, and the peak was at 6-12 h. Expression of all cytokines declined on 48 h after SE.Our findings suggested that SE lead to increased expression of IL-1, IL-1ra and IL-1R1 after lithium-pilocarpine-induced seizures, indicating that cytokines involved in SE and brain impairment after seizure.
Abstract Background: Low-temperature environments can strongly affect the normal growth and health of livestock. Previous studies have shown that cold exposure can alter the intestinal microbiota and thereby affect other traits. In winter, cold weather can be accompanied by strong winds that aggravate the effects of cold on livestock. In this study, an experiment was conducted to investigate the effect of low temperature and wind speed on physiological indexes, rumen microbiota, and immune responses in sheep. Methods: The sheep were divided into control group and test group according to their ambient temperature.Sheep in the test group were divided into four groups according to wind-speed treatment: no wind (average wind velocity less than 0.5 m/s), low wind velocity (average wind velocity of 3 m/s), medium wind velocity (average wind velocity of 4 m/s) and high wind velocity (average wind velocity of 5 m/s). Results: Average daily gain and the utilization of forage, especially soluble fiber, decreased with increasing wind velocity in cold temperature ( P <0.05). In rumen, the enzyme activity of cellulose degradation was also lowerwith increasing wind velocity ( P <0.05). The abundance of potentially beneficial bacteria showed differedamong the wind treatments ( P <0.05).The large fluctuations in the amount of bacteria provided a breeding opportunity forpotentially harmful bacteria ( P <0.05). In addition, there were significant decreases in the serum levels of IL-2 and IFN-γ ( P <0.05) and a large increase in IL-4 level ( P <0.05), which indicated that the sheep underwent immune suppressionduring the trial. The significant increase in the activities of the antioxidant enzymes SOD, GSH-PX, and CAT ( P <0.05) indicated that the production of oxygen free radicals was increased. Conclusions: The cold environment significantly reduced the growth of sheep and altered the composition of rumen microbiota, reducing the utilization of soluble fiber by the rumen flora. Furthermore, the sheep produced large amounts of enzymes to resist tissue damage and experienced immune suppression in the cold environment.
Objective To observe the effect of simvastatine and fenofibrate on adipose serum triglyceride lipase(ATGL) and TNF-α levels in rats with non-alcoholic fatty acid liver disease(NAFLD).Methods Seventy-eight male SD rats were randomly divided into normal group(n=15) and NAFLD model group(n=63).Rats in normal control group were fed with normal diet and those in NAFLD model group were fed with high-fat diet.Their serum TG and TC levels were measured at the end of 12 weeks.After a rat NAFLD model was established,the rats in NAFLD model group were randomly divided into NAFLD control group,simvastatine treatment group,fenofibrate treatment group,and diet group.The animals were killed and their serum TG,TC,ALT,AST,BUN,Scr,fasting blood glucose(FBG),TNF-α and ATGL levels were measured at the end 16 weeks,their liver index was counted,and their liver pathologic changes were observed.Results The serum TNF-α and ATGL levels were 290±78 and 332±89,0.69±0.21 and 0.63±0.20,485±115 and 0.43±0.22,respectively,in simvastatine treatment group,fenofibrate treatment group and NAFLD model group(P 0.05,P 0.01).The liver pathological lesions were significantly improved in simvastatine treatment group and fenofibrate treatment group.The serum ATGL and TNF-α levels were significantly higher in diet group than in NAFLD control group(0.52±0.19 vs 0.43±0.22,P 0.05).The serum TNF-α level was negatively related with the serum ATGL level(r=0.948,P 0.01).Conclusion Serum ATGL activity is closely correlated with serum TNF-α level in rats with NAFLD.Simvastatine and fenofibrate can increase the ATGL activity by decreasing the serum TNF-α level,thus effectively alleviating NAFLD.
Purpose To evaluate the feasibility of T 1 rho mapping in myocardium at 3T and to determine whether T 1 rho mapping could better characterize myocardial injury in end‐stage renal disease (ESRD) patients compared to T 1 and T 2 mapping. Materials and Methods T 1 rho mapping, T 1 mapping, and T 2 mapping were performed at 3T on 35 healthy volunteers (15 males, 20 females, 40.7 ± 13.6 years) and 32 ESRD patients (16 males, 16 females, 48.6 ± 11.9 years). The mean T 1 rho, T 1 , and T 2 values were compared using Student's t ‐test and correlated with cardiac function parameters, including peak ejection rate (PER), short‐axis percent thickening (SAPT), peak filling rate (PFR), and time to peak filling (TTPF). Results The mean T 1 rho values (49.4 ± 2.6 msec vs. 52.2 ± 4.0 msec, P = 0.001) and T 2 values (50.5 ± 2.5 msec vs. 54.1 ± 4.0 msec, P < 0.001) were significantly different between the volunteers and patients, but there were no significant differences between the two groups in the T 1 values (1253.1 ± 71.6 msec vs. 1273.4 ± 41.7 msec, P = 0.157). The mean T 1 rho values were negatively correlated with the PER ( r = –0.397; P = 0.03), SAPT ( r = –0.688; P < 0.001), and PFR ( r = –0.537; P = 0.002), whereas positively correlated with the TTPF ( r = 0.677; P < 0.001). The mean T 2 values were negatively correlated only with the SAPT ( r = –0.427; P = 0.019) in the ESRD patients. Conclusion T 1 rho mapping of the myocardium is feasible at 3T. T 1 rho values are higher in ESRD patients and relate to cardiac function, which may better characterize myocardial injury than can T 1 and T 2 . J. Magn. Reson. Imaging 2016;44:723–731.
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