One-pot synthesis of α-bromoacetals of ketones from secondary alcohols and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) in ethylene glycol

<p>α-Bromoacetals of ketones were prepared from various secondary alcohols with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) and ethylene glycol through oxidation, bromination, and acetalization in one pot without the use of other catalysts under mild conditions. The effects of DBDMH, the solvent, and <i>N</i>-bromosuccinimide on the reaction were investigated. Under the optimal conditions, most α-bromoacetals of ketones were obtain in 90–98% yields.</p

Antibiotic-Loaded Chitosan Hydrogel with Superior Dual Functions: Antibacterial Efficacy and Osteoblastic Cell Responses

It is critical for the clinical success to take the biological function into consideration when integrating the antibacterial function into the implanted biomaterials. To this aim, we prepared gentamycin sulfate (GS)-loaded carboxymethyl-chitosan (CM-chitosan) hydrogel cross-linked by genipin. The prepared hydrogels not only achieved superb inhibition on bacteria growth and biofilm formation of <i>Staphylococcus aureus</i> but also significantly enhanced the adhesion, proliferation, and differentiation of MC3T3-E1 cells. The observed dual functions were likely based on the intrinsic property of the positive charged chitosan-based hydrogel, which could be modified to selectively disrupt the bacteria wall/membrane and promote cell adhesion and proliferation, as suggested by the membrane permeability study. The genipin concentration played an important role in controlling the degradation time of the chitosan hydrogel and the MC3T3-E1 cell responses. The loading of GS not only significantly increased the antibacterial efficiency but also was beneficial for the osteoblastic cell responses. Overall, the biocompatibility of the prepared chitosan-GS hydrogel could be tuned with both the genipin and GS concentrations, which control the available positive charged sites of chitosan. The results demonstrated that chitosan-GS hydrogel is an effective and simple approach to achieving combined antibacterial efficacy and excellent osteoblastic cell responses, which has great potential in orthopedic applications

Electrospun PCL/Gelatin composite fibrous scaffolds: mechanical properties and cellular responses

<p>Electrospinning of hybrid polymer has gained widespread interest by taking advantages of the biological property of the natural polymer and the mechanical property of the synthetic polymer. However, the effect of the blend ratio on the above two properties has been less reported despite the importance to balance these two properties in various tissue engineering applications. To this aim, we investigated the electrospun PCL/Gelatin composite fibrous scaffolds with different blend ratios of 4:1, 2:1, 1:1, 1:2, 1:4, respectively. The morphology of the electrospun samples was observed by SEM and the result showed that the fiber diameter distribution became more uniform with the increase of the gelatin content. The mechanical testing results indicated that the 2:1 PCL/Gelatin sample had both the highest tensile strength of 3.7 MPa and the highest elongation rate of about 90%. Surprisingly, the 2:1 PCL/Gelatin sample also showed the best mesenchymal stem cell responses in terms of attachment, spreading, and cytoskeleton organization. Such correlation might be partly due to the fact that the enhanced mechanical property, an integral part of the physical microenvironment, likely played an important role in regulating the cellular functions. Overall, our results indicated that the PCL/Gelatin sample with the blend ratio of 2:1 was a superior candidate for scaffolds for tissue engineering applications.</p

LINC02163 regulates growth and epithelial-to-mesenchymal transition phenotype via miR-593-3p/FOXK1 axis in gastric cancer cells

<p>Recently, long non-coding RNAs (lncRNAs) were involved in promoting gastric cancer (GC) initiation and progression. In the current study, we revealed that the expression level of LINC02163 was elevated in GC cell lines and tissues. Knockdown of LINC02163 inhibited GC cells growth and invasion both <i>in vitro</i> and <i>in vivo</i>. Mechanismly, LINC02163 exerted as a ceRNA and negatively regulated miR-593-3p expression. In addition, FOXK1 was identified as a down-stream target of miR-593-3p. The miR-593-3p/FOXK1 axis mediated LINC02163’s effect on GC. To the best of our knowledge, our findings provided the first evidence that LINC02163 functioned as an oncogene in GC. LINC02163 may be a candidate prognostic biomarker and a target for new therapies in GC patients.</p

Succinic Acid Based Biodegradable Thermoplastic Poly(ester urethane) Elastomers: Effects of Segment Ratios and Lengths on Physical Properties

Biodegradable thermoplastic poly­(ester urethane) (PEU) elastomers containing poly­(diethylene glycol succinate) (PDGS) and poly­(butylene succinate) (PBS) were synthesized by chain extension of dihydroxyl terminated PDGS and PBS precursors with 4,4′-methylenediphenyl diisocyanate as a chain extender. The structure, molecular weight, and physical properties of the PEUs were investigated by ¹H NMR, GPC, DSC, WAXD, DMA, and tensile tests. The results suggest that the compositions affect the physical properties more significantly than the segment lengths. The PEU containing 28.2 wt % PBS showed the best mechanical properties with ultimate strength and elongation at break of 41 MPa and 1503%, respectively. Both the storage modulus and Young’s modulus increased significantly with increasing PBS segment content, which was reasonably ascribed to the increasing degree of crystallinity. The hysteresis value increased with PBS segment content while it decreased slightly with lengths of both hard and soft segments, which were also attributed to the different crystallization behaviors of the PEUs

Associations of Genetic Variants in the <i>PSCA</i>, <i>MUC1</i> and <i>PLCE1</i> Genes with Stomach Cancer Susceptibility in a Chinese Population

<div><p>Background</p><p>Several genetic variants including <i>PSCA</i> rs2294008 C>T and rs2976392 G>A, <i>MUC1</i> rs4072037 T>C, and <i>PLCE1</i> rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).</p><p>Methods</p><p>To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.</p><p>Results</p><p>In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with <i>PSCA</i> rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), <i>PSCA</i> rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or <i>PLCE1</i> rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, <i>MUC1</i> rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.</p><p>Conclusions</p><p>This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.</p></div

Urethane Ionic Groups Induced Rapid Crystallization of Biodegradable Poly(ethylene succinate)

Novel urethane ionic groups were incorporated into biodegradable poly­(ethylene succinate) (PES) by chain extension reaction of PES diol (HO–PES–OH) and diethanolamine hydrochloride (DEAH) using hexamethylene diisocyanate (HDI) as a chain extender. The synthesized polymer was a novel segmented poly­(ester urethane) ionomer (PESI) in which the soft segments were formed by reaction of HO–PES–OH with HDI and the hard segments that contained ionic groups were derived from reaction of DEAH with HDI. The crystallization rate of PESI was dramatically accelerated when 3 mol % urethane ionic groups were incorporated. However, the crystallization mechanism did not change. The significant acceleration in crystallization rate was attributed to the improved nucleation efficiency by incorporation of the urethane ionic group, because PESI showed significantly enhanced nucleation density but slightly slowed spherurlitic growth rate in comparison with PES which was synthesized by chain extension reaction of HO–PES–OH with HDI. The increased nucleation efficiency was ascribed to the aggregation of hard segments of PESI induced by the ionic interactions

Distribution of <i>MTHFR</i> C677T genotypes and allelic frequencies in acute myeloid leukemia patients.

<p><i>MTHFR</i>, methylenetetrahydrofolate reductase; OR, odds ratio; CI, confidence interval; vs., versus; HWE, Hardy-Weinberg equilibrium.</p

Publication bias test (<i>MTHFR</i> C677T: T <i>vs.</i> C).

<p>Publication bias test (<i>MTHFR</i> C677T: T <i>vs.</i> C).</p

Novel Inhibitors of Human DOPA Decarboxylase Extracted from <i>Euonymus glabra</i> Roxb.

Dopamine, a biogenic amine with important biological functions, is produced from l-DOPA by DOPA decarboxylase (DDC). DDC is a potential target to modulate the production of dopamine in several pathological states. Known inhibitors of DDC have been used for treatment of Parkinson’s disease but suffered low specificity and diverse side effects. In the present study, we identified and characterized a novel class of natural-product-based selective inhibitors for DDC from the extract of <i>Euonymus glabra</i> Roxb. by a newly developed high-throughput enzyme assay. The structures of these inhibitors are dimeric diarylpropane, a unique chemical structure containing a divalent dopamine motif. The most effective inhibitors <b>5</b> and <b>6</b> have an IC₅₀ of 11.5 ± 1.6 and 21.6 ± 2.7 μM in an <i>in vitro</i> purified enzyme assay, respectively, but did not inhibit other homologous enzymes. Compound <b>5</b> but not <b>6</b> dose-dependently suppressed the activity of hDDC and dopamine levels at low micromolar concentrations in cells. Furthermore, structure–activity relationship analyses revealed that <i>p</i>-benzoquinone might be a crucial moiety of these inhibitors for inhibiting hDDC. The natural-product-based selective inhibitors of hDDC could serve as a chemical lead for developing improved drugs for dopamine-related disease states