Discovery of novel arylamide derivatives containing piperazine moiety as inhibitors of tubulin polymerisation with potent liver cancer inhibitory activity.

In this work, a series of novel arylamide derivatives containing piperazine moiety were designed and synthesised as tubulin polymerisation inhibitors. Among 25 target compounds, compound () exhibited low nanomolar IC values ranging from 0.089 to 0.

Charged multivesicular body protein 2B ameliorates biliary injury in the liver from donation after cardiac death rats via autophagy with air-oxygenated normothermic machine perfusion.

Normothermic machine perfusion (NMP) could provide a curative treatment to reduce biliary injury in donation after cardiac death (DCD) donor livers; however, the underlying mechanisms remain poorly understood. In a rat model, our study compared air-oxygenated NMP to hyperoxygenated NMP and found that air-oxygenated NMP improved DCD functional recovery. Here, we found that the charged multivesicular body protein 2B (CHMP2B) expression was substantially elevated in the intrahepatic biliary duct endothelium of the cold-preserved rat DCD liver after air-oxygenated NMP or in biliary endothelial cells under hypoxia/physoxia.

E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

Background And Aims: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear.

Approach And Results: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes.

Interaction analysis of gene variants related to one-carbon metabolism with chronic hepatitis B infection in Chinese patients.

Background: The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one-carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one-carbon metabolic pathway and CHB infection.

Methods: A case-control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.

Tripartite Motif-Containing 27 Attenuates Liver Ischemia/Reperfusion Injury by Suppressing Transforming Growth Factor β-Activated Kinase 1 (TAK1) by TAK1 Binding Protein 2/3 Degradation.

Background And Aims: Hepatic ischemia-reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation (LT). As a critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif-containing (TRIM) 27 in hepatic I/R injury remains worthy of study.

Approach And Results: This study systemically evaluated the putative role of TRIM27/transforming growth factor β-activated kinase 1 (TAK1)/JNK (c-Jun N-terminal kinase)/p38 signaling in hepatic I/R injury.

Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation.

Hepatocellular carcinoma (HCC), a type of malignant liver tumor, has a grim prognosis. As a functional protein, synaptopodin-2 (SYNPO2) has been associated with malignancy; however, the expression profile and function of SYNPO2 in HCC remains unknown. Herein, we revealed that SYNPO2 was transcriptionally downregulated in HCC tissues from both The Cancer Genome Atlas cohort and our cohort, and was also decreased at the translational level as determined by western blotting and immunohistochemical staining.

Six-Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia-Reperfusion Injury by Suppressing Transforming Growth Factor-β-Activated Kinase 1.

Background And Aims: Hepatic ischemia-reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six-transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types.

Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.

Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells.

Suppression of BRD4 inhibits human hepatocellular carcinoma by repressing MYC and enhancing BIM expression.

Bromodomain 4 (BRD4) is an epigenetic regulator that, when inhibited, has anti-cancer effects. In this study, we investigated whether BRD4 could be a target for treatment of human hepatocellular carcinoma (HCC). We show that BRD4 is over-expressed in HCC tissues.

GABAB receptor antagonist CGP46381 inhibits form-deprivation myopia development in guinea pigs.

The aim was to investigate the effects of the GABAB receptor antagonist, CGP46381, on form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25). The deprived eyes were treated with daily subconjunctival injections (100 μl) of either 2% CGP46381, 0.

[Study on the effect of vibsane-type diterpenoids of Viburnum odoratissimum on human HepG2 cell growth and its underlying mechanism].

Objective: To study the antiproliferation effect on HepG2 cells and its underlying mechanism of the active chemical composition of the Viburnum Odoratissimum.

Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and trypan blue dye exclusion assay were used to assess the effect of vibsane-type diterpenoids on the proliferation of various tumor cells. Alterations in cell cycle and apoptosis were determined by flowcytometry.

[Evaluation of an indirect immunofluorescence assay kit for the detection of anti-Toxoplasma gondii IgG].

Objective: To develop an indirect immunofluorescence assay (IFA) kit for detecting anti-Toxoplasma gondii IgG.

Methods: Based on the established IFA method, we established an IFA kit for the detection of human T. gondii infection.

[Changes of alveolar macrophage phagocytosis and TNF-alpha, IL-6 of rats with Pneumocystis pneumonia].

Objective: To observe the changes of alveolar macrophage (AM) phagocytosis and the levels of TNF-alpha and IL-6 in AM supernatants and bronchoalveolar lavage fluid (BALF) of rats with Pneumocystis pneumonia (PCP).

Methods: Wistar rats were injected with dexamethasone intramuscularly and continually to establish the model of PCP, the AM phagocytosis and levels of TNF-alpha and IL-6 in AM supernatants and BALF of rats with PCP were detected, meanwhile, the normal controls were set.

Results: The phagocyting percentage [(20.

[Biomechanical comparison of three methods of internal fixation for distal femoral fractures].

Objective: To compare the biomechanics of three internal fixations for distal femoral fractures,and to choose suitable clinical internal fixation according to experimental date.

Methods: The fracture models of femoral condydle were made on 12 fresh cadaver femurs (C1 type of AO classification). The fractures were fixed by supracondylar intramedullary interlocking nails (A), L-shaped condyle plates (B) and compressed plates (C) respectively.

[In vivo effect of dihydroartemisinin and azithromycin on the ultrastructure of Toxoplasma gondii tachyzoites].

Thirty Kunming mice were randomly divided into three groups named as dihydroartemisinin roup (A), dihydroartemisinin and azithromycin group (B), and control group (C). Each mouse was infected intraperitoneally with 2x10(3) Toxoplasma gondii tachyzoites. Eight hours after infection, the mice of groups A and B were treated twice a day for 4 days with 75 mg/kg of dihydroartemisinin.

[Association of genetic polymorphisms and haplotypes in hMLH1 and hMSH3 gene with the risk of papillary thyroid carcinoma].

Objective: To explore the relationship of the genetic polymorphisms and the haplotypes in hMLH1 and hMSH3 gene with the risk of papillary thyroid carcinoma (PTC) in Chinese Hans.

Methods: A hospital based 1:1 matched case-control study was carried out. The polymorphisms for 204 pairs of PTC cases and healthy controls were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific oligonucleotide (PCR-ASO) assays.

[Determination of trace elements in hair of mice infected with Trichinella spiralis].

Mice were divided into 3 groups: heavy infection group with 80 mice each was fed with 400 muscle larvae of Trichinella spiralis, light infection group with 60 mice each was fed by 200 larvae, and uninfected control (60 mice) . The content of Cu, Zn and Fe in the dorsal hair samples was measured in the week of 1, 3, 5, 7, 9, 11, 13 and 15 after infection. Results indicated that the content of Zn, Cu and Fe in the two experimental groups reduced considerably in comparison to the control (P < 0.

[Enzyme change in bronchoalveolar lavage fluid of pneumocystis pneumonia rats and the effect of garlicin treatment].

Objective: To study the change of enzymes and effect of garlicin treatment on the change in bronchoalveolar lavage fluid (BALF) of rats with Pneumocystis carinii pneumonia (PCP).

Methods: Wistar rats were injected intramuscularly continually with dexamethasone to establish the rat model of PCP. The experimental rats (group A) were injected intramuscularly with garlicin at a dose of 10 mg/(kg x d) for 5 days in the 3rd, 6th and 9th week respectively, and SMZ/TMP therapy group (B), PCP infected group (C) and normal group (D) were established as controls.

[A matched case-control study of papillary thyroid carcinoma].

Objective: In order to explore the risk factors of the papillary thyroid carcinoma(PTC), a hospital-based matched case-control study was carried out in Shanghai.

Methods: Matched by gender, age (+/- 3 years old) and native place,205 pairs of cases and controls were recruited and studied. Database was established with Epi Info 6.

[The experimental study of garlicin in treating Pneumocystis carinii pneumonia in rats].

Objective: To assess the therapeutic effect of garlicin on Pneumocystis carinii pneumonia (PCP) of immunosuppressed rats.

Methods: The Wistar rats were injected intramuscularly continually with dexamethasone for eight weeks to establish the rat model of PCP. The rats were treated with garlicin, meanwhile control groups without treatment and with SMZ-TMP treatment were established respectively in PCP model.

[Single nucleotide polymorphisms and point mutations of ataxia telangiectasia mutated gene in Chinese of Han ethnicity].

Objective: To explore the single nucleotide polymorphisms (SNPs) and point mutations of ataxia telangiectasia mutated (ATM) gene in Chinese of Han ethnicity.

Methods: The target fragments of the exon 39, exon 61 and exon 63 of ATM gene were first amplified using PCR technique, then screened for the SNPs and point mutations using single strand conformation polymorphism (SSCP) technique, finally the representative bands were sequenced for the verification of the new single nucleotide polymorphisms and point mutations using the automatic DNA sequencing technique.

Results: Six new SNPs were found in the exon 39, intron 61 and intron 63 of ATM gene.

[Genetic polymorphisms in X-ray repair cross-complementing gene 1 and susceptibility to papillary thyroid carcinoma].

Objective: To study the association of polymorphisms in the X-ray repair cross-complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC).

Methods: A hospital based, matched case-control study was carried out. The polymorphisms in XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP.