The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis.

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer.

AIM: Hypermethylation of the promoter of the hMLH1 gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer. METHODS: Data were obtained from a hospital-based, case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors. Hypermethylation of the hMLH1 gene promoter, polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated. RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene. Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation, whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region. Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53 gene. CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hypermethylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.

Kimchi and soybean pastes are risk factors of gastric cancer.

AIM: This case-control study investigated the effects of kimchi, soybean paste, fresh vegetables, nonfermented alliums, nonfermented seafood, nonfermented soybean foods, and the genetic polymorphisms of some metabolic enzymes on the risk of gastric cancer in Koreans. METHODS: We studied 421 gastric cancer patients and 632 age- and sex-matched controls. Subjects completed a structured questionnaire regarding their food intake pattern. Polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1) and aldehyde dehydrogenase 2 (ALDH2) were investigated. RESULTS: A decreased risk of gastric cancer was noted among people with high consumption of nonfermented alliums and nonfermented seafood. On the other hand, consumption of kimchi, and soybean pastes was associated with increased risk of gastric cancer. Individuals with the CYP1A1 Ile/Val or Val/Val genotype showed a significantly increased risk for gastric cancer. Increased intake of kimchi or soybean pastes was a significant risk factor for the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the GSTM1 non-null, the GSTT1 non-null, or the ALDH2 *1/*1 genotype. In addition, eating soybean pastes was associated with the increased risk of gastric cancer in individuals with the GSTM1 null type. Nonfermented alliums were significant in individuals with the CYP1A1 Ile/Ile, the CYP2E1 c1/c2 or c2/c2, the GSTT1 null, the GSTT1 non-null, or the ALDH2 *1/*2 or *2/*2 genotype, nonfermented seafood was those with the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the ALDH2 *1/*1 genotype or any type of GSTM1 or GSTT1. In homogeneity tests, the odds ratios of eating kimchi for gastric cancer according to the GSTM1 or GSTT1 genotype were not homogeneous. CONCLUSION: Kimchi, soybean pastes, and the CYP1A1 Ile/Val or Val/Val are risk factors, and nonfermented seafood and alliums are protective factors against gastric cancer in Koreans. Salt or some chemicals contained in kimchi and soybean pastes, which are increased by fermentation, would play important roles in the carcinogenesis of stomach cancer. Polymorphisms of the CYP1A1, CYP2E1, GSTM1, GSTT1, and ALDH2 genes could modify the effects of some environmental factors on the risk of gastric cancer.

Tryptophan hydroxylase polymorphism is associated with age of onset of alcoholism related behaviors.

The purpose of this study was to explore the association of a tryptophan hydroxylase gene polymorphism (TPH1 A218C) with the age of alcoholism onset in a Korean population. The genotype and allele frequencies of TPH1 were investigated in 182 male hospitalized patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for alcohol dependence. Alcoholics with the TPH1 AA or AC genotypes had an earlier age of disease onset (median age of onset, 26.5 years) than those with the CC genotype (median age of onset, 30 years; p=.002). Age of onset has been used in classifying alcoholics. The TPH1 polymorphism may explain, in part, the biological basis for these typologies.

[Discussion on thoughts and methods for treatment of diabetic nephropathy by TCM according to inflammatory pathogenesis].

Aim of this article was to investigate relationship between inflammatory pathogenesis of diabetic nephropathy and the TCM pathogenetic theory of Shen-Collateral impaired by Toxin, and to illustrate the method for removing toxin, activating collateral and protecting Shen can be an effective treatment for inhibiting the inflammatory pathogenesis of diabetic nephropathy.

[Effect of combined therapy of xiaoke shen'an capsule and western medicine in diabetic nephropathy].

OBJECTIVE: To observe the therapeutic effect of xiaoke shen' an capsule on diabetic nephropathy. METHODS: Ninety patients with diabetic nephropathy were randomly divided into two groups, the patients in the control group (CG) were treated with conventional western medicine, and those in the treated group (TG) were treated with combined therapy of xiaoke shen'an capsule and conventional western medicine. The treatment course of both groups was 8 weeks, and the therapeutic effect related indexes were measured before and after treatment. RESULTS: The curative rate was 85.0% and 73.3% in CG and TG respectively, it was better in TG than that in CG (P < 0.05). Indexes such as fasting blood glucose, glycosylated hemoglobin, blood pressure, quantity of 24h urinary protein, urinary albumin excretion rate, renal function, blood lipids and hemoreheologic parameters were significantly different before and after treatment in TG (P < 0.05 or P < 0.01). As compared with CG, some of these indexes after treatment were superior to those in CG (P < 0.01 or P < 0.05). CONCLUSION: Combined therapy of xiaoke shen'an capsule and conventional western medicine has definite therapeutic effect on diabetic nephropathy.

Identification of antibacterial and antioxidant constituents of the essential oils of Cynanchum chinense and Ligustrum compactum.

The aim of this research was to determine the chemical composition, antioxidant and antibacterial properties of the essential oils from Cynanchum chinense and Ligustrum compactum and isolation of antioxidant and antibacterial constituents from the essential oils. Thirty-eight components were identified in essential oils. Based on bioactivity-guided fractionation, guaiacol, linalool and 2-phenylethanol were isolated and identified as active constituents. Both L. compactum flower oil and 2-phenylethanol showed high antibacterial performance, with inhibition zone from 22.8 ± 0.8 to 11.9 ± 2.0 mm at highest concentration, and minimum inhibitory concentration values ranging from 0.25% to 1%. In both DPPH and ABTS assay, the active constituent guaiacol (IC50 = 4.15 ± 0.72 and 9.12 ± 0.98 µg mL(-1), respectively) exhibited high antioxidant activity, and the oils showed moderate antioxidant activity. These results indicate potential efficacy of active constituents and essential oils of L. compactum and C. chinense to control food-borne pathogenic and spoilage bacteria.

Evidence for an N-glycosylation polymorphism of arylsulfatase a predisposing to alcoholism in Koreans.

This study investigated the possible effect of the pseudodeficient N-glycosylation polymorphism of the arylsulfatase A (ASA) gene on alcohol dependence among Koreans. Alcoholic patients (N=123) were more likely than control subjects to be heterozygous or homozygous for the ASA pseudodeficient N-glycosylation site (36% of alcoholics versus 20% of controls; P<0.01). Among these 123 alcoholic patients, 42 alcoholics were heterozygous and two were homozygous for the ASA pseudodeficient N-glycosylation polymorphism. This result provides evidence that the ASA pseudodeficient N-glycosylation site allele increases the risk of alcohol dependence within a Korean population.

Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p<.001) and in smokers (p<.01), and with the 2-naphthol level in non-smokers (p<.01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

The association of subjective stress, urinary catecholamine concentrations and PC game room use and musculoskeletal disorders of the upper limbs in young male Koreans.

The use of PCs can cause health problems, including musculoskeletal disorders (MSDs) of the upper limbs. This study was performed to investigate whether using PCs in PC game rooms may induce MSDs of the upper limbs. 284 young male Koreans were included. A self-administered, structured questionnaire was used to gather information about game room use, perceived subjective stress, and the symptoms related to MSDs. Urinary concentrations of epinephrine, norepinephrine, and dopamine were measured in spot urine. The symptom prevalence of MSDs of the upper limbs increased according to the increase of the duration of game room use. The intensity of perceived subjective stress showed a significant dose-response relationship with the frequency of MSDs symptoms in neck and shoulder areas. However, the urinary level of catecholamines was not significantly correlated with the symptom prevalence of MSDs in the upper limbs. These findings suggest that using PCs in game rooms produce physical stress on the upper limbs, strong enough to induce MSDs.