Roxarsone inhibits hepatic stellate cell activation and ameliorates liver fibrosis by blocking TGF-ß1/Smad signaling pathway.

Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-ß1 (TGF-ß1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl4-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-ß1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.

Effects of Oleic Acid Addition Methods on the Metabolic Flux Distribution of Ganoderic Acids R, S and T's Biosynthesis.

The effects of oleic acid addition methods on the metabolic flux distribution of ganoderic acids R, S and T's biosynthesis from Ganoderma lucidum were investigated. The results showed that adding filter-sterilized oleic acid in the process of submerged fermentation and static culture is of benefit to the synthesis of ganoderic acids R, S and T. The metabolic fluxes were increased by 97.48%, 78.42% and 43.39%, respectively. The content of ganoderic acids R, S and T were 3.11 times, 5.19 times and 1.44 times higher, respectively, than they were in the control group, which was without additional oleic acid. Ganoderic acids R, S and T's synthesis pathways (GAP), tricarboxylic acid cycles (TCA), pentose phosphate pathways (PP) and glycolysis pathways (EMP) were all enhanced in the process. Therefore, additional oleic acid can strengthen the overall metabolic flux distribution of G. lucidum in a submerged fermentation-static culture and it can reduce the accumulation of the by-product mycosterol. This study has laid an important foundation for improving the production of triterpenes in the submerged fermentation of G. lucidum.

[3-dimensional visualization study of angle nerve of facial nerve].

OBJECTIVE: To validate the previous anatomic study result about angle nerve of facial nerve through 3-dimensional (3-D) visualization technique, so as to provide theory basis for clinic treatment of nerve loss. METHOD: The full-thickness soft tissue at internal side of inner canthus was harvested from adult cadaveric head. The skin was 3 cm in length and 1 cm in width, with 2 parallel cut lines as location markers. The specimen was sliced continuously into 120 slices, with 10 microm in thickness for every slice, 0.25 mm apart. The slices underwent HE staining and 2-D digital image was gained by high resolution scanner. Then 3-D reconstruction was performed. RESULTS: (1) It showed the 3-D structures and routes of angle nerve, as well as the relationship between angle nerve and angle arteriovenous. All the reconstructed structures can be displayed together or separately, also from any angles. (2) It confirmed the accuracy of microscopic anatomy study about angle nerve. (3) The 3-D reconstruction of angle nerve, as well as the surrounding structure could be very useful for clinical application. CONCLUSION: Based on the histologic study and computer technology, the 3-D reconstruction of angle nerve could provide accurate basis for the feasibility of clinic treatment of angle nerve loss.

[Anatomic study of malar fat pad and aging analysis].

OBJECTIVE: To discuss the midface aging mechanism through anatomic study of malar fat pad. METHODS: 10 fresh adult cadaveric heads (20 sides) fixed by vascular perfusion of formalin were used for anatomic study with microsurgery technique under microscope. The midfacial ligament and connective tissue between skin and subcutaneous fat were observed carefully in different parts of midface. The location, shape and extent of malar fat pad was also recorded and photographed. RESULTS: The malar fat pad has a triangle shape. The bottom is a curve along the orbicularis retaining ligament at the lower eyelid. The fat pad is extended internally to the nasolabial fold and labiomandibular fold, externally from the major zygomatic muscle end point at the malar surface to the angulus oris and submandibular edge. (2) The malar fat pad is composed of meshed fibrous tissue, with big fat particles in it. It becomes tight when being stretched in horizontal direction along nasolabial fold and loosen when being stretched in vertical direction. (3) There is tight connection between skin and fat pad, which is divided into four areas as I, II, III, IV. The areas I, II, III are strip-shaped parelled to the nasolabial fold. The area IV is a irregular quadrilateral. (4) There are six fixation ligaments between malar fat pad and deep tissue: orbicularis retaining ligament upper layer of lower eyelid, orbicularis retaining ligament substratum of lower eyelid, zygomaticus ligament, zygomatic cutaneous ligament, zygomatic cutaneous ligament substratum, platysma There are four closely connected areas cutaneous forward ligament, cheek maxilla ligament. CONCLUSIONS: between the facial skin and malar fat pad which makes malar fat pad and skin keep relatively consistent. The malar fat pad moving down mainly resulted from slack of ligaments support which is one of the reasons for aging face.

Polymorphisms in genes HSD17B1 and HSD17B2 and uterine leiomyoma risk in Chinese women.

PURPOSE: To evaluate the association of HSD17B1 and HSD17B2 gene polymorphisms with uterine leiomyoma in Chinese women. METHODS: 121 Chinese women with clinically diagnosed uterine leiomyoma and 217 healthy normal Chinese women were investigated to compare three single nucleotide polymorphisms (SNPs) (rs605059 and rs676387 of HSD17B1 gene and rs8191246 of HSD17B2 gene) by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing method. RESULTS: All the SNPs were polymorphisms in Chinese women. Frequencies of rs605059 AA genotype and A allele were significantly increased in patients with uterine leiomyoma compared to healthy controls (GG vs. AA, OR 0.40, 95 % CI 0.20-0.82; G vs. A, OR 0.68, 95 % CI 0.50-0.94). CONCLUSION: The results suggest that the genotype of HSD17B1 rs605059 may play a role in the tumourgenesis of uterine leiomyoma.

Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis.

BACKGROUND AND OBJECTIVES: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. METHODS: In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. RESULTS: The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19-1.65; for GSTT1: OR = 1.30; 95%CI, 1.05-1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18-2.51). CONCLUSION: These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population.

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.

Association between SNPs in pre-miRNA and risk of chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airway obstruction and persistent chronic airway inflammation and is influenced by genetic and environmental factors. This study aimed to explore the genetic aspect of its initial occurrence. DESIGN AND METHODS: We conducted a case-control study of 432 COPD patients and 511 control subjects frequency-matched in age and gender distribution. We genotyped three single nucleotide polymorphisms (SNPs) in pre-miRNAs using a PCR-RFLP assay and evaluated their relevance to COPD susceptibility. RESULTS: We found that the TT genotype and T allele of miR-196a2 rs11614913 were significantly associated with a decreased risk for COPD, compared with the CC genotype and C allele. Similarly, the GG genotype and G allele of miR-499 rs3746444 were associated with a decreased risk for COPD, compared with the AA genotype and A allele. CONCLUSIONS: These findings suggest that both rs11614913 and rs3746444 may be involved in susceptibility to COPD.

Association of tumor necrosis factor gene polymorphisms with susceptibility to dilated cardiomyopathy in a Han Chinese population.

Tumor necrosis factor (TNF) is an immunomodulatory cytokine that plays an important role in many inflammatory and autoimmune diseases. We investigated the correlation between single-nucleotide polymorphisms of the TNF gene [i.e., TNF-α (308), TNF-α (857), TNF-α (863), TNF-α (1031), and TNF-ß (+252)] and dilated cardiomyopathy (DCM). A total of 110 DCM patients and 110 control subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism and DNA-sequencing assay. GA=AA genotypes of TNF-α (308) were significantly associated with increased risk of DCM compared with GG genotype (odds ratio[OR]=1.92; 95% confidence intervals [CI], 1.05-3.52). Similarly, GA=AA of TNF-ß (+252) was significantly associated with increased risk of DCM compared with GG genotype (OR=1.97; 95% CI, 1.14-3.38). Additionally, A allele of TNF-α (-308) and TNF-ß (+252) was associated with a 1.76-fold increased risk of DCM compared with G allele (OR=1.76; 95% CI, 1.05-2.95 and OR=1.79; 95% CI, 1.22-2.63, respectively). However,no association between DCM and TNF-α (857), TNF-α (1031), and TNF-α (863) was observed. TNF gene polymorphisms may be associated with risk of DCM.