Timorsaponin C

Epsilonproteobacterial hydroxylamine oxidoreductase (epsilonHao): characterization of a 'missing link' in the multihaem cytochrome c family.[Pubmed:28388834]

Mol Microbiol. 2017 Jul;105(1):127-138.

Members of the multihaem cytochrome c family such as pentahaem cytochrome c nitrite reductase (NrfA) or octahaem hydroxylamine oxidoreductase (Hao) are involved in various microbial respiratory electron transport chains. Some members of the Hao subfamily, here called epsilonHao proteins, have been predicted from the genomes of nitrate/nitrite-ammonifying bacteria that usually lack NrfA. Here, epsilonHao proteins from the host-associated Epsilonproteobacteria Campylobacter fetus and Campylobacter curvus and the deep-sea hydrothermal vent bacteria Caminibacter mediatlanticus and Nautilia profundicola were purified as epsilonHao-maltose binding protein fusions produced in Wolinella succinogenes. All four proteins were able to catalyze reduction of nitrite (yielding ammonium) and hydroxylamine whereas hydroxylamine oxidation was negligible. The introduction of a tyrosine residue at a position known to cause covalent trimerization of Hao proteins did neither stimulate hydroxylamine oxidation nor generate the Hao-typical absorbance maximum at 460 nm. In most cases, the epsilonHao-encoding gene haoA was situated downstream of haoC, which predicts a tetrahaem cytochrome c of the NapC/NrfH family. This suggested the formation of a membrane-bound HaoCA assembly reminiscent of the menaquinol-oxidizing NrfHA complex. The results indicate that epsilonHao proteins form a subfamily of ammonifying cytochrome c nitrite reductases that represents a 'missing link' in the evolution of NrfA and Hao enzymes.

Three new C-27-carboxylated-lupane-triterpenoid derivatives from Potentilla discolor Bunge and their in vitro antitumor activities.[Pubmed:28388692]

PLoS One. 2017 Apr 7;12(4):e0175502.

Three new lupane-triterpenoids (1-3) along with six known compounds (4-9) were isolated from the ethanolic extract of whole plant of Potentilla discolor Bunge. The structures of Compounds 1-3 were established by extensive 1D and 2D NMR together with other spectrum analysis, indicating that their C-27 positions were highly oxygenated, which were rarely found in nature. Their in vitro anti-proliferative activities against HepG-2, MCF-7 and T-84 cell lines were evaluated by Cell Counting Kit-8 (CCK-8) assay, and the results showed different activities for three cell lines with IC50 values ranging from 17.84 to 40.64 muM. In addition, the results from Hoechst 33258 and AO/EB staining as well as annexinV-FITC assays exhibited Compound 1 caused a markedly increased HepG-2 cellular apoptosis in a dose-dependent manner. The further mechanisms of Compound 1-induced cellular apoptosis were confirmed that 1 induced the production of ROS and the alteration of pro- and anti-apoptotic proteins, which led to the dysfunction of mitochondria and activation of caspase-9 and caspase-3 and finally caused cellular apoptosis. These results would be useful in search for new potential antitumor agents and for developing semisynthetic lupane-triterpenoid derivatives with high antitumor activity.

Salicylic acid peeling combined with vitamin C mesotherapy versus salicylic acid peeling alone in the treatment of mixed type melasma: A comparative study.[Pubmed:28388246]

J Cosmet Laser Ther. 2017 Oct;19(5):294-299.

INTRODUCTION: Melasma is a distressing condition for both dermatologists and patients. We evaluated the effectiveness of salicylic acid (SA) peel and vitamin C mesotherapy in the treatment of melasma. MATERIALS AND METHODS: Fifty female patients were divided into two groups. All patients were treated with 30% SA peel every two weeks for two months. In addition, after SA peeling Group A was intradermally administered 10 vitamin C on the melasma lesion at 1-cm intervals. All patients were followed up for 6 months, during which the recurrence rates were evaluated. Digital photographs of the melasma site were taken and patients' Melasma Area and Severity Index (MASI) scores were assessed. After the treatment, the patients were asked to complete the melasma quality of life questionnaire (MelasQoL) to evaluate their satisfaction with the treatment. All the adverse effects were noted. RESULTS: The MelasQoL and MASI scores of patients in both groups significantly decreased after the treatment. Apart from a burning sensation, no adverse event was observed and all patients tolerated the treatment well. DISCUSSION: SA peel combined with vitamin C mesotherapy is a safe and effective alternative for the treatment of melasma with no significant side effects and minimal downtime.

The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus.[Pubmed:28388281]

Endocr Res. 2017 Nov;42(4):331-335.

AIM: Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls. MATERIALS AND METHODS: For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated. RESULTS: Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes. CONCLUSIONS: Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.