Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing

Introduction: Slow wound repair in diabetes is a serious adverse event that often results in loss of a limb or disability. An advanced and encouraging vehicle is wanted to enhance clinically applicable diabetic wound care. Nanofibrous insulin/vildagliptin core-shell biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffolds to prolong the effective drug delivery of vildagliptin and insulin for the repair of diabetic wounds were prepared.Methods: To fabricate core-shell nanofibrous membranes, vildagliptin mixture with PLGA, and insulin solution were pumped via separate pumps into two differently sized capillary tubes that were coaxially electrospun.Results and Discussion: Nanofibrous core-shell scaffolds slowly released effective vildagliptin and insulin over 2 weeks in vitro migration assay and in vivo wound-healing models. Water contact angle (68.3 ± 8.5° vs. 121.4 ± 2.0°, p = 0.006) and peaked water absorbent capacity (376% ± 9% vs. 283% ± 24%, p = 0.003) of the insulin/vildagliptin core-shell nanofibrous membranes remarkably exceeded those of a control group. The insulin/vildagliptin-loaded core-shell nanofibers improved endothelial progenitor cells migration in vitro (762 ± 77 cells/mm2 vs. 424.4 ± 23 cells/mm2, p < 0.001), reduced the α-smooth muscle actin content in vivo (0.72 ± 0.23 vs. 2.07 ± 0.37, p < 0.001), and increased diabetic would recovery (1.9 ± 0.3 mm2 vs. 8.0 ± 1.4 mm2, p = 0.002). Core-shell insulin/vildagliptin-loaded nanofibers extend the drug delivery of insulin and vildagliptin and accelerate the repair of wounds associated with diabetes

Widespread translational control contributes to the regulation of Arabidopsis photomorphogenesis

Environmental light regulates and optimizes plant growth and development. Genomic profiling of polysome-associated mRNA reveals that light stimulates dramatic changes in translational regulation, which contribute more to light-induced gene expression changes than transcriptional regulation

Functional analysis of novel SNPs and mutations in human and mouse genomes

<p>Abstract</p> <p>Background</p> <p>With the flood of information generated by the new generation of sequencing technologies, more efficient bioinformatics tools are needed for in-depth impact analysis of novel genomic variations. FANS (Functional Analysis of Novel SNPs) was developed to streamline comprehensive but tedious functional analysis steps into a few clicks and to offer a carefully designed presentation of results so researchers can focus more on thinking instead of typing and calculating.</p> <p>Results</p> <p>FANS <url>http://fans.ngc.sinica.edu.tw/</url> harnesses the power of public information databases and powerful tools from six well established websites to enhance the efficiency of analysis of novel variations. FANS can process any point change in any coding region or GT-AG splice site to provide a clear picture of the disease risk of a prioritized variation by classifying splicing and functional alterations into one of nine risk subtypes with five risk levels.</p> <p>Conclusion</p> <p>FANS significantly simplifies the analysis operations to a four-step procedure while still covering all major areas of interest to researchers. FANS offers a convenient way to prioritize the variations and select the ones with most functional impact for validation. Additionally, the program offers a distinct improvement in efficiency over manual operations in our benchmark test.</p

Top A_FB at the Tevatron vs. charge asymmetry at the LHC in chiral U(1) flavor models with flavored Higgs doublets

We consider the top forward-backward (FB) asymmetry at the Tevatron and top charge asymmetry at the LHC within chiral U(1)^\prime models with flavor-dependent U(1)^\prime charges and flavored Higgs fields, which were introduced in the ref. [65]. The models could enhance not only the top forward-backward asymmetry at Tevatron, but also the top charge asymmetry at LHC, without too large same-sign top pair production rates. We identify parameter spaces for the U(1)^\prime gauge boson and (pseudo)scalar Higgs bosons where all the experimental data could be accommodated, including the case with about 125 GeV Higgs boson, as suggested recently by ATLAS and CMS.Comment: 11 pages, 6 figures, figures and discussion adde

Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization

Probing topcolor-assisted technicolor from top charge asymmetry and triple-top production at the LHC

In a topcolor-assisted technicolor model (TC2) with large FCNC top quark couplings, we study its correlated contributions to the top quark forward-backward asymmetry ($A_{FB}$) at the Tevatron, the top charge asymmetry ($A_{C}$) and the triple-top production at the LHC. Under current constraints on the top quark from the LHC and Tevatron(such as the total and differential production rates), we scan the parameter space of such a TC2 model. We find that in the allowed parameter space the TC2 model can explain the Tevatron measured $A_{FB}$ at $2\sigma$ level, but meanwhile significantly enhance $A_{C}$ at the LHC. Such enhanced $A_{C}$, albeit currently allowed by the LHC measurement at $2\sigma$ level, will serve as a test of TC2 with the improvement of measurement precision at the LHC. Then with all the constraints (including the requirement to explain $A_{FB}$ at $2\sigma$ level and satisfying the current LHC measurement of $A_{C}$ at $2\sigma$ level), we find that the TC2 model can induce sizable triple-top production at the 14 TeV LHC (the production rate can maximally reach 16 pb). Due to the low SM backgrounds, the triple-top production can also be a good probe for TC2 model, complementary to $A_{C}$.Comment: 15 pages, 5 figures, new constraints from LHC addded, published version(Phys. Lett. B

Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the Wjj

We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model, which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the same sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.Comment: 40 pages, 10 figures, added 1 figure and extended discussion, accepted for publication in JHE

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice