The Ste2p receptor for alpha-factor, a tridecapeptide mating pheromone of the yeast Saccharomyces cerevisiae, belongs to the G protein-coupled family of receptors. In this paper we report on the synthesis of peptides corresponding to five of the seven transmembrane domains (M1-M5) and two homologues of the sixth transmembrane domain corresponding to the wild-type sequence and a mutant sequence found in a constitutively active receptor. The secondary structures of all new transmembrane peptides and previously synthesized peptides corresponding to domains 6 and 7 were assessed using a detailed CD analysis in trifluoroethanol, trifluoroethanol-water mixtures, sodium dodecyl sulfate micelles, and dimyristoyl phosphatidyl choline bilayers. Tryptophan fluorescence quenching experiments were used to assess the penetration of the membrane peptides into lipid bilayers. All peptides were predominantly (40-80%) helical in trifluoroethanol and most trifluoroethanol-water mixtures. In contrast, two of the peptides M3-35 (KKKNIIQVLLVASIETSLVFQIKVIFTGDNFKKKG) and M6-31 (KQFDSFHILLINleSAQSLLVPSIIFILAYSLK) formed stable beta-sheet structures in both sodium dodecyl sulfate micelles and DMPC bilayers. Polyacrylamide gel electrophoresis showed that these two peptides formed high molecular aggregates in the presence of SDS whereas all other peptides moved as monomeric species. The peptide (KKKFDSFHILLIMSAQSLLVLSIIFILAYSLKKKS) corresponding to the sequence in the constitutive mutant was predominantly helical under a variety of conditions, whereas the homologous wild-type sequence (KKKFDSFHILLIMSAQSLLVPSIIFILAYSLKKKS) retained a tendency to form beta-structures. These results demonstrate a connection between a conformational shift in secondary structure, as detected by biophysical techniques, and receptor function. The aggregation of particular transmembrane domains may also reflect a tendency for intermolecular interactions that occur in the membrane environment facilitating formation of receptor dimers or multimers.

The propose of this review was to summarize the advances in multi-scale surface technology of titanium implants to accelerate the osseointegration process. The several multi-scaled methods used for improving wettability, roughness, and bioactivity of implant surfaces are reviewed. In addition, macro-scale methods (e.g., 3D printing (3DP) and laser surface texturing (LST)), micro-scale (e.g., grit-blasting, acid-etching, and Sand-blasted, Large-grit, and Acid-etching (SLA)) and nano-scale methods (e.g., plasma-spraying and anodization) are also discussed, and these surfaces are known to have favorable properties in clinical applications. Functionalized coatings with organic and non-organic loadings suggest good prospects for the future of modern biotechnology. Nevertheless, because of high cost and low clinical validation, these partial coatings have not been commercially available so far. A large number of in vitro and in vivo investigations are necessary in order to obtain in-depth exploration about the efficiency of functional implant surfaces. The prospective titanium implants should possess the optimum chemistry, bionic characteristics, and standardized modern topographies to achieve rapid osseointegration.

Depending on the requirements of specific applications, implanted materials including metals, ceramics, and polymers have been used in various disciplines of medicine. Titanium and its alloys as implant materials play a critical role in the orthopedic and dental procedures. However, they still require the utilization of surface modification technologies to not only achieve the robust osteointegration but also to increase the antibacterial properties, which can avoid the implant-related infections. This article aims to provide a summary of the latest advances in surface modification techniques, of titanium and its alloys, specifically in biomedical applications. These surface techniques include plasma spray, physical vapor deposition, sol-gel, micro-arc oxidation, etc. Moreover, the microstructure evolution is comprehensively discussed, which is followed by enhanced mechanical properties, osseointegration, antibacterial properties, and clinical outcomes. Future researches should focus on the combination of multiple methods or improving the structure and composition of the composite coating to further enhance the coating performance.

BackgroundMicroRNAs regulate gene expression at the post-transcriptional level and involved in diverse biological and pathological processes, including tumorigenesis. Rs11614913 in miR-196a2 and rs2910164 in miR-146a are shown to associate with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association.Methodology/Principal FindingsWe assessed published studies of the association between these microRNA polymorphisms and cancer risk from eleven studies with 16,771 subjects for miR-196a2 and from ten studies with 15,126 subjects for miR-146a. As for rs11614913, the contrast of homozygote (TT vs CC: OR = 0.92, 95% CI = 0.85–0.99, P heterogeneity = 0.45), allele (T vs C: OR = 0.96, 95% CI = 0.92–0.99, P heterogeneity = 0.61) and recessive model (OR = 0.90, 95% CI = 0.84–0.97, P heterogeneity = 0.50) produced statistically association. Subgroup analysis by ethnicity, statistically significantly decreased cancer risks were found among Asians for allele contrast (OR = 0.95, 95% CI = 0.90–0.99, P heterogeneity = 0.74) and the recessive genetic model (OR = 0.90, 95% CI = 0.82–0.98, P heterogeneity = 0.85). According to subgroup analysis by tumor types, the protective effect of C/T polymorphism was only found in breast cancer under allele contrast (T vs C: OR = 0.94, 95% CI = 0.88–0.99, P heterogeneity = 0.26). For rs2910164, no significant associations were found among overall analysis model with relatively large heterogeneity. Through the stratified analysis, heterogeneity decreased significantly. In the subgroup analyses by cancer types, the C allele of rs2910164 was associated with protection from digestive cancer in allele contrast (C vs G: OR = 0.86, 95% CI = 0.77–0.96, P heterogeneity = 0.51).Conclusions/SignificanceOur meta-analysis suggests that the rs11614913 most likely contributes to decreased susceptibility to cancer, especially in Asians and breast cancer. Besides, the C allele of the rs2910164 might be associated with a protection from digestive cancer.

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With the increasing demand for bone implant therapy, titanium alloy has been widely used in the biomedical field. However, various potential applications of titanium alloy implants are easily hampered by their biological inertia. In fact, the interaction of the implant with tissue is critical to the success of the implant. Thus, the implant surface is modified before implantation frequently, which can not only improve the mechanical properties of the implant, but also polish up bioactivity and osseoconductivity on a cellular level. This paper aims at reviewing titanium surface modification techniques for biomedical applications. Additionally, several other significant aspects are described in detail in this article, for example, micromorphology, microstructure evolution that determines mechanical properties, as well as a number of issues concerning about practical application of biomedical implants.