Aprocitentan is a dual endothelin receptor antagonist.Based on the effective evidence of Ⅲ phases of clinical trials,the drug was approved for marketing by the U.S.Food and Drug Administration on March 19,2024 for the treatment of refractory hypertension.At present,multiple clinical studies have confirmed that Aprocitentan has excellent antihypertensive effects and good tolerability.This article reviews the pharmacological effects,preclinical.

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Colitis, Ulcerative ; drug therapy ; Dextran Sulfate ; Drugs, Chinese Herbal ; pharmacology ; Glycyrrhiza ; chemistry ; Mice ; Plant Extracts ; pharmacology ; Tripterygium ; chemistry

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

OBJECTIVETo explore the feasibility of evaluating complete ischemia-reperfusion injury (IRI) of the testis by contrast-enhanced ultrasonography with microbubbles (MB) targeted to P-selectin (MBp) in rabbits.

METHODSWe randomly divided 30 healthy adult rabbits into five groups of equal number (control, 0.5 h IRI, 1 h IRI, 2 h IRI, and 4 h IRI), prepared phospholipid MB and MBp, and performed contrast-enhanced ultrasonography of the bilateral testes with MB or MBp at an interval of 20 min at different times after IRI. When MB or MBp disappeared completely in the healthy testis at 4 to 5 min after intravenous injection, we recorded the power of the first frame (F-P) in the IRI testes followed by immunohistochemical staining of the testis tissue.

RESULTSCEU with MBp achieved a significantly higher F-P than that with MB in all the IRI groups (P < 0.05), which was (8.34 +/- 1.20) versus (1.87 +/- 0.25) 10(-5) AU at 2 hours, but there was no significant difference between MB and MBp in the control rabbits (0 AU, P > 0.05). Immunohistochemistry showed a significantly time-dependent increase in the expression of P-selectin in the vascular endothelial cells of the IRI testes, but not in those of the control.

CONCLUSIONContrast-enhanced ultrasonography with MBp can be used to evaluate the inflammatory reaction of testicular ischemia-reperfusion injury.

Animals ; Antibodies ; Disease Models, Animal ; Male ; Microbubbles ; P-Selectin ; immunology ; Rabbits ; Reperfusion Injury ; diagnostic imaging ; Testis ; blood supply ; Ultrasonography

OBJECTIVETo explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats.

METHODSRicin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups.

RESULTSThe TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01).

CONCLUSIONIntratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

Animals ; Antineoplastic Agents ; administration & dosage ; Apoptosis ; drug effects ; CD4-CD8 Ratio ; Disease Models, Animal ; Female ; Gels ; therapeutic use ; Immunohistochemistry ; Immunomodulation ; drug effects ; Injections, Intralesional ; Interleukin-2 ; immunology ; metabolism ; Mammary Neoplasms, Experimental ; drug therapy ; immunology ; pathology ; Random Allocation ; Rats ; Rats, Wistar ; Ricin ; administration & dosage ; Sensitivity and Specificity ; Temperature ; Tumor Necrosis Factor-alpha ; immunology ; metabolism

AIMThe changes of tissue inhibitor of metalloproteinase-4 (TIMP-4) expression in mouse ovary during pregnant and postpartum period were studied to investigate the role of TIMP-4 in corpus luteum (CL).

METHODSRT-PCR was used to deter mine the change of TIMP-4 mRNA and indirect immunofluorescence was used to observe the change of TIMP-4 protein. The expression of TIMP-4 mRNA was observed in various periods throughout the stage of pregnancy and postpartum day 1.

RESULTSThe expression of TIMP-4 was gradually enhanced from day 1 to day 8, reached a maximal expression at day 8, while decreased at day 11 and to the lowest level at postpartum day 1. Indirect immunofluorescence results further indicated that TIMP-4 protein was localized to CL and theca-intera cells in various periods throughout the pregnancy and postpartum day 1. In addition, the change pattern of TIMP-4 protein agreed with that of the TIMP-4 mRNA in pregnancy CL.

CONCLUSIONThe expression of TIMP-4 in mouse ovary during pregnancy and postpartum is in spatio-temporal pattern and it may be involved in the formation and function maintain of CL during pregnancy in mice.

Animals ; Female ; Mice ; Mice, Inbred Strains ; Ovary ; metabolism ; Postpartum Period ; Pregnancy ; RNA, Messenger ; genetics ; Tissue Inhibitor of Metalloproteinases ; metabolism

OBJECTIVETo discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB).

METHODSUltrasonographic variables were analyzed in 110 CHB patients. An ultrasonic semi-quantitative scoring system using seven ultrasonic morphologic parameters, a Fisher discriminating function and three quantitative ultrasonic parameters was developed. The performance of these methods was also studied and compared.

RESULTSThe areas under the curve of the scoring system for different liver fibrosis stages were >or= S2: 0.946, >or= S3: 0.914, and S4: 0.915. The total score was well correlated with the histological stage of fibrosis (r=0.824, P < 0.001). There was a significant difference between the stages of fibrosis. The accuracy of the Fisher discriminating function for identifying three study endpoints was 76.5%, 78.2% and 67.3%. Combining the ultrasonic scoring system and the discriminating function, the specificity was 85%-90% and the accuracy was 77%-84%.

CONCLUSIONOur ultrasonic semi-quantitative scoring system is a noninvasive method for quantitating liver fibrosis. If it is used together with a discriminating function, the accuracy of diagnosing liver fibrosis can be significantly increased.

Adolescent ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; diagnostic imaging ; Humans ; Liver Cirrhosis ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Ultrasonography, Doppler, Color ; Young Adult

OBJECTIVEMost of the therapeutic strategies for systemic inflammatory response syndrome (SIRS) is not effective. This study was to investigate the effect of continuous veno-venous hemodiafiltration (CVVHDF) on SIRS induced by cecum perforate peritonitis in piglets.

METHODSTwelve piglets (weighing 7-9 kg) were randomly divided into two groups: control and CVVHDF (n=6). The piglets of both groups were subjected to a cecum puncture to induce peritonitis which caused SIRS. After SIRS occurred the piglets of the CVVHDF group immediately received the CVVHDF therapy for 6 hrs, with a blood flow rate of 20 mL/min, a replacement rate of 300 mL/h, and a dialysis rate of 600 mL/h. The heart rate (HR), mean artery blood pressure (MABP), respiratory rate (RR), arterial blood gas analysis and blood cells count were measured and recorded at baseline and onset of SIRS, and 2, 4 and 6 hrs after SIRS occurred.

RESULTSWhen SIRS occurred, the HR and RR increased and the MABP, artery oxygen pressure (PaO2) and the count of white cells decreased in both groups. The HR of the CVVHDF group decreased significantly at 2 hrs (P < 0.05) and remained lower until 6 hrs after CVVHDF therapy (P < 0.01) compared with that of the control group. The RR of the CVVHDF group was significantly lower than that of the control group 6 hrs after CVVHDF therapy (P < 0.05). The MABP of the CVVHDF group increased significantly 4 and 6 hrs after therapy compared with that of the control group (P < 0.01, P < 0.05 respectively). There were no significant differences in temperature, PaO2 and blood cells count between the two groups during the experiment.

CONCLUSIONSCVVHDF has a positive effect on hemodynamics in piglets with SIRS induced by cecum perforate peritonitis.

Animals ; Blood Pressure ; Body Temperature ; Carbon Dioxide ; blood ; Cecum ; injuries ; Central Venous Pressure ; Female ; Heart Rate ; Hemodiafiltration ; Intestinal Perforation ; complications ; Male ; Oxygen ; blood ; Peritonitis ; complications ; Swine ; Systemic Inflammatory Response Syndrome ; therapy

Collagen Type I ; biosynthesis ; Hepatocyte Growth Factor ; biosynthesis ; Hepatocytes ; cytology ; metabolism ; physiology ; Liver Cirrhosis ; metabolism ; pathology ; physiopathology ; Liver Regeneration ; Receptors, Vitronectin ; biosynthesis

Adult ; Aged ; Blood Coagulation Factors ; analysis ; Case-Control Studies ; Female ; Hepatitis B, Chronic ; diagnosis ; pathology ; physiopathology ; Humans ; Male ; Middle Aged ; Prothrombin Time ; Young Adult