Humans ; Liver Neoplasms ; metabolism ; pathology

To study the immunopathological characteristics and differential diagnosis of hepatic angiomyolipoma(AML).Methods:Thirty-six surgically resected hepatic AML were investigated clinicopathologically and immunohistochemically with 10 antibodies.Results:Hepatic AML occurred in 21 females and 15 males,with the mean age of 41.6 years(26-60 years old).The patients with AML often had no special symptoms even had large space-occupying lesions in the liver.The diameter of AML was 2.5 cm to 14 cm(mean 6.8 cm).Histologically,AML was composed of varying heterogeneous mixture of 3 tissue components:blood vessels,smooth muscle and adipose cells.Extramedullary hemopoiesis sometimes existed.According to tissue components,AML was subcategorized into mixed type(19.4%,n=7),lipomatous type(11.1%,n=4),myomatous type(66.7%,n=24),and angiomatous type(2.8%,n=1).The epithelioid smooth muscle cells were sensitive to HMB-45(100%),SMA(100%),and CD117(66.7%) staining.Conclusion:Hepatic AML often contains smooth muscle elements,which have varied morphological features and should be carefully differentiated from hepatocellular carcinoma,mesenchymal hamartoma，and tumors with rich fat or blood vessels.Immunohistochemical staining with HMB-45 and SMA are the best available markers for the diagnosis of hepatic AML.

Ginseng saponins are a type of important active substances in the ginseng genus plants. They have notable pharmacological activities of antineoplastic, neuroprotective, and hepatoprotective activities, which have been drawn more attention to obtain minor ginsenosides by all kinds of methods. In this review, we discussed the latest progress for enrichment of minor ginsenosides by biological transformation of major ginsenosides. At the same time, we have a brief outlook of the research at bioconversion of ginseng saponins.
Bacteria ; metabolism ; Biotransformation ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Ginsenosides ; chemistry ; metabolism ; Panax ; chemistry ; metabolism

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

OBJECTIVETo investigate the effect of ulinastatin on renal function and ultrastructure changes after renal ischemia-reperfusion in rats.

METHODSAcute ischemic renal injury model was established (45 min of bilateral renal ischemia and reperfusion for 24 h). Thirty Male SD rats were randomly divided into 3 groups: sham operation group (control group or group C, without renal ischemia), renal ischemia-reperfusion group (ischemia-reperfusion group or group I, without ulinastatin), renal ischemia-reperfusion and ulinastatin intravenous injection group (ulinastatin group or group U). BUN level, serum creatinine values and renal ultrastructure were measured.

RESULTSSerum creatinine (167 +/- 39) micromol/L and BUN concentration (21 +/- 7) mmol/L in group I were significantly higher than those in group U: serum creatinine (116 +/- 13) micromol/L and BUN concentration (14.1 +/- 2.6) mmol/L (P < 0.05). The renal ultrastructure was greatly injured in group I, meanwhile, it was obviously ameliorated in group U.

CONCLUSIONUlinastatin greatly improved renal function and provides remarkable protection on renal ultrastructure after ischemia-reperfusion of kidney in rats.

Animals ; Glycoproteins ; pharmacology ; Kidney ; blood supply ; drug effects ; ultrastructure ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; pathology

OBJECTIVETo evaluate the possible association of the MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma (HCC) in a Chinese population.

METHODSFive hundred and eight HCC cases and 543 controls were studied. The MTHFR genotypes were determined using a PCR-based restriction fragment length polymorphism (RFLP) method. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential HCC risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotypes and HCC risks.

RESULTSNo overall significant difference in genotype distribution was found when comparing all HCC cases to controls (P = 0.258). However, a significantly increased risk of HCC was observed among T/T homozygotes (adjusted OR = 1.66, 95% CI = 1.08-2.54, P<0.05) compared to C-allele carriers (CC or CT). When stratified with sex, this trend was more prominent in females, but not in males. Females who were homozygous (T/T) for the C677T polymorphism were at a 2.64-fold (95% CI = 1.19-5.88, P<0.05) increased risk of developing HCC when compared to C-allele carriers. However in males, T/T homozygotes had a similar risk with C-allele carriers.

CONCLUSIONThe MTHFR C677T polymorphism may be associated with a higher HCC risk in females, but not in males in this population.

Aged ; Carcinoma, Hepatocellular ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Liver Neoplasms ; genetics ; Logistic Models ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic

Humans ; Liver Neoplasms ; pathology ; surgery ; Pathology, Surgical

BACKGROUNDTreatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.

METHODSHuman glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.

RESULTSMild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).

CONCLUSIONVPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.

Apoptosis ; drug effects ; radiation effects ; Blotting, Western ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Dacarbazine ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Glioma ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Valproic Acid ; pharmacology

OBJECTIVETo study the features of micro satellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).

METHODSTen high-polymorphic micro satellite markers on chromosome 4 were selected to be detected for loss of heterozygosity (LOH), micro satellite instability (MSI) and allelic imbalance (AI) in 56 HCC using PCR-simple sequence length polymorphism (PCR-SSLP) analysis.

RESULTSLOH was found in 40 of 56 HCC (71.4%) on at least 1 locus, the top two loci were D4S426 (61%), D4S1534 (53.7%). LOH on D4S406 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg. Similarly, LOH on D4S1538 occurred more frequently in patients with HBsAg negative than those with HBsAg positive [76.9% (20/26) vs 12.5% (2/16), chi2=13.999, P<0.01]. LOH on D4S426, D4S1615 and D4S165 were more frequent in poorly or moderately differentiated HCC than in well-differentiated HCC [76.7%(23/30) vs 18.2%(2/11), chi2=9.242, P<0.01; 53.8% (14/26) vs 16.7% (2/12), P<0.05; 60.7% (17/28) vs 18.2% (2/11), P<0.01]. LOH on loci D4S2921 was more frequently detected in tumors with intrahepatic metastasis than in those without [63.6% (21/33) vs 18.2% (2/11), chi2=5.132, P<0.01]. MSI was found in 8.9% (5/56) cases. AI was found in 26.8% (15/56) of all cases examined.

CONCLUSIONFrequent micro satellite alterations on chromosome 4 were existed in HCC. LOH, which represents tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis of HCC; MSI, representing mismatch repair gene pathway, arranges as the next.

Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; Chromosomes, Human, Pair 4 ; Female ; Humans ; Liver Neoplasms ; genetics ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged

OBJECTIVETo investigate the effects of two fluid resuscitations on the bacterial translocation and the inflammatory factors of small intestine in rats with hemorrhagic shock.

METHODSFifty SD healthy male rats were randomly divided into 5 groups (n equal to 10 per group): Group A (Sham group), Group B (Ringer's solution for 1 h), Group C (Ringer's solution for 24 h), Group D (hydroxyethyl starch for 1 h) and Group E ((hydroxyethyl starch for 24 h). A model of rats with hemorrhagic shock was established. The bacterial translocation in liver, content of tumor necrosis factor-alpha (TNF-alpha) and changes of myeloperoxidase enzyme (MPO) activities in small intestine were pathologically investigated after these two fluid resuscitations, respectively.

RESULTSThe bacterial translocation and the expression of TNF-alpha in the small intestine were detected at 1 h and 24 h after fluid resuscitation. There were significant increase in the number of translocated bacteria, TNF-alpha and MPO activities in Group C compared with Group B, significant decrease in Group E compared with Group D and in Group B compared with Group D. The number of translocated bacteria and TNF-alpha expression significantly decreased in Group E as compared with Group C.

CONCLUSIONSThe bacterial translocation and the expression of TNF-alpha in the small intestine exist 24 h after fluid resuscitation. 6% hydroxyethyl starch can improve the intestinal mucosa barrier function better than the Ringer's solution.

Animals ; Bacterial Translocation ; drug effects ; Fluid Therapy ; Hydroxyethyl Starch Derivatives ; administration & dosage ; pharmacology ; Intestine, Small ; metabolism ; Isotonic Solutions ; administration & dosage ; pharmacology ; Male ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; therapy ; Tumor Necrosis Factor-alpha ; metabolism