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Abstract: The interaction of tanshinone IIA and human serum albumin (HSA) has been characterised by molecular modelling, fluorescence, Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopic methods. The results of molecular modelling suggested that tanshinone IIA located within the binding pocket of subdomain IIA of HSA is held mainly by hydrophobic forces. Fluorescence titration revealed that tanshinone IIA could quench the intrinsic fluorescence of HSA. The binding constants at three temperatures (296, 303, and 310)K are (6.42·104, 1.54·105, and 4.35·105)dm3 ·mol−1, respectively. In addition, the studies of CD spectroscopy and FT-IR spectroscopy showed that the binding of tanshinone IIA to HSA changed molecular conformation of HSA. [Copyright &y& Elsevier]

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic. [Display omitted] • Gut microbiota is involved in TP-induced liver injury. • LGG supplementation could ameliorates TP hepatotoxicity. • LGG-mediated BA metabolism plays a vital role in TP hepatotoxicity. • The protective role of LGG in TP hepatotoxicity by regulating the BA-FXR Axis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Accumulating studies indicate that HPV E6/E7 oncoproteins interacting genes, TP53, BRCA1 and BARD1, play a critical role in cervical carcinogenesis. We hypothesized that potentially functional polymorphisms in TP53, BRCA1 and BRAD1 may individually and/or jointly contribute to cervical cancer risk. Methods: We genotyped 4 single nucleotide polymorphisms (SNPs) with amino acid changes, TP53 Pro72Arg (rs1042522), BRCA1 Pro871Leu (rs799917), BARD1 Pro24Ser (rs1048108) and Arg378Ser (rs2229571), in a case-control study of 404 cervical cancer cases and 404 cancer-free controls in Chinese women. Results: Logistic regression analysis showed that the BRCA1 variant rs799917 TT genotype was associated with a significantly decreased risk of cervical cancer in a recessive genetic model (adjusted OR=0.62, 95% CI=0.40–0.95), compared with the genotypes CT/CC. However, no significant associations with cervical cancer were observed for other 3 SNPs (adjusted OR=1.01, 95% CI=0.68–1.50 for rs1048108 TT vs CT/CC; adjusted OR=1.04, 95% CI=0.67–1.64 for rs2229571 CC vs GG/GC; adjusted OR=0.84, 95% CI=0.59–1.20 for rs1042522 CC vs GG/GC). Conclusion: These findings indicate that BRCA1 rs799917 polymorphism may contribute to the risk of cervical cancer in this Chinese population, and further validation in other populations are warranted. [Copyright &y& Elsevier]

Abstract: Objective: Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Herein, we evaluated whether genetic variants of HLA-DP and HLA-DQ are associated with cervical cancer risk. Methods: We genotyped four single nucleotide polymorphisms (SNPs) in HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs2856718 and rs7453920) in a two-stage case–control study with a total of 2317 cervical cancer cases and 2109 cancer-free controls using TaqMan allelic discrimination assay. Results: We found consistently significant associations of HLA-DP rs3077 and rs9277535 with increased risks of cervical cancer (dominant genetic model: adjusted OR=1.51, 95% CI=1.32–1.71 for rs3077; adjusted OR=1.29, 95% CI=1.12–1.49 for rs9277535). When combining the effects of HLA-DP rs3077 and rs9277535, subjects carrying “≥1” variant alleles had a 1.55-fold increased risk of cervical cancer (95% CI=1.32–1.81), compared with those carrying “0” variant allele. And cervical cancer risk significantly increased with the increasing number of variant alleles of the two SNPs in a dose-dependent manner (P for trend=4.33×10−10). However, there were no significant associations for HLA-DQ rs2856718 and rs7453920 in our population. Conclusions: These findings indicate that HLA-DP rs3077 and rs9277535 were candidate susceptibility markers for cervical cancer in Chinese females. Further validation studies with different ethnic background, biological function analyses and especially HPV typing together were needed. [Copyright &y& Elsevier]

Coastal upwelling that brings to the surface both CO 2 - and nutrient-rich deep seawater is related to acidification and intense biological productivities in surface waters. However, the impact of biological activities on upwelling-induced acidification from nearshore to offshore areas in an upwelling zone remains insufficiently known. In this paper, we present daily records of high-resolution profiles of carbonate chemistry and hydrographic parameters from the nearshore to the offshore upwelling zone off the east coast of Hainan Island (ECH) in July 2014 (summer season). A three end-member mixing model was adopted to discriminate biological processes from physical mixing and to further semiquantitatively diagnose biological contribution to the upwelling-induced acidification. The results show divergent responses in pH, aragonite saturation state (Ω Ar) and biomediated nonconservative dissolved inorganic carbon (ΔDIC) at depths of 10 m–30 m between nearshore and offshore regimes under the on-going coastal upwelling, which were attributed to the distinct roles of biological activities in mediating acidification in the upper 30 m across the ECH. Specifically, in the offshore regime, enhanced photosynthesis reduced the upwelling-induced acidification by 40% (i.e., type C: relief role), whereas aerobic respiration increased acidification in the subsurface waters of the nearshore regime by 15% (i.e., type B: aggravation role). This led to the pH and Ω Ar minimum in upwelled waters along the transect from the nearshore to the offshore. In contrast, the biological contribution was almost negligible over surface waters in the nearshore regime because of the balance between net community productivity and net community calcification (i.e., type A: limited or minor role). • Three types of biological contribution to upwelling-induced acidification are quantitatively revealed at the east coast of Hainan Island. • Behaviors of carbonate chemistry and dissolved oxygen in upwelled waters are distinct between the nearshore and offshore regimes. • Aerobic respiration intensifies acidification in the subsurface of the nearshore area during a coastal upwelling. [ABSTRACT FROM AUTHOR]