Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone

Expression Profiling of Calcium Induced Genes in Cultured Human Keratinocytes

Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. To examine the gene expression profile in calcium-induced keratinocyte differentiation, we constructed a normalized cDNA library using mRNA isolated from these calcium-treated keratinocytes. After sequencing about 10,000 clones, we were able to obtain 4,104 independent genes. They consisted of 3,699 annotated genes and 405 expressed sequence tags (ESTs). Some were the genes involved in constituting epidermal structures and others were unknown genes that are probably associated with keratinocytes. In particular, we were able to identify genes located at the chromosome 1q21, the locus for the epidermal differentiation complex, and 19q13.1, another probable locus for epidermal differentiation-related gene clusters. One EST located at the chromosome 19q13.1 showed increased expression by calcium treatment, suggesting a novel candidate gene relevant to keratinocyte differentiation. These results demonstrate the complexity of the transcriptional profile of keratinocytes, providing important clues on which to base further investigations of the molecular events underlying keratinocyte differentiation

No association between polymorphisms of WNT2 and schizophrenia in a Korean population

<p>Abstract</p> <p>Background</p> <p>Wingless-type MMTV integration site family member 2 (WNT2) has a potentially important role in neuronal development; however, there has yet to be an investigation into the association between single nucleotide polymorphisms (SNPs) of <it>WNT2 </it>and schizophrenia. This study aimed to determine whether certain SNPs of <it>WNT2 </it>were associated with schizophrenia in a Korean population.</p> <p>Methods</p> <p>e genotyped 7 selected SNPs in the <it>WNT2 </it>gene region (approximately 46 Kb) using direct sequencing in 288 patients with schizophrenia and 305 healthy controls.</p> <p>Results</p> <p>Of the SNPs examined, one SNP showed a weak association with schizophrenia (p = 0.017 in the recessive model). However, this association did not remain statistically significant after Bonferroni correction.</p> <p>Conclusion</p> <p>The present study does not support a major role for <it>WNT2 </it>in schizophrenia. This could be due to the size of the population. Therefore, additional studies would be needed to definitively rule out the gene's minor effects.</p

Myelin-Weighted Imaging Presents Reduced Apparent Myelin Water in Patients with Alzheimer&rsquo;s Disease

The purpose of this study was to investigate myelin loss in both AD and mild cognitive impairment (MCI) patients with a new myelin water mapping technique within reasonable scan time and evaluate the clinical relevance of the apparent myelin water fraction (MWF) values by assessing the relationship between decreases in myelin water and the degree of memory decline or aging. Twenty-nine individuals were assigned to the cognitively normal (CN) elderly group, 32 participants were assigned to the MCI group, and 31 patients were assigned to the AD group. A 3D visualization of the short transverse relaxation time component (ViSTa)-gradient and spin-echo (GraSE) sequence was developed to map apparent MWF. Then, the MWF values were compared between the three participant groups and was evaluated the relationship with the degree of memory loss. The AD group showed a reduced apparent MWF compared to the CN and MCI groups. The largest AUC (area under the curve) value was in the corpus callosum and used to classify the CN and AD groups using the apparent MWF. The ViSTa-GraSE sequence can be a useful tool to map the MWF in a reasonable scan time. Combining the MWF in the corpus callosum with the detection of atrophy in the hippocampus can be valuable for group classification

Electronic Alteration on Oligothiophenes by <i>o</i>‑Carborane: Electron Acceptor Character of <i>o</i>‑Carborane in Oligothiophene Frameworks with Dicyano-Vinyl End-On Group

We studied electronic change in oligothiophenes by employing <i>o</i>-carborane into a molecular array in which one or both end(s) were substituted by electron-withdrawing dicyano-vinyl group(s). Depending on mono- or bis-substitution at the <i>o</i>-carborane, a series of linear A₁-D-A₂ (<b>1a</b>–<b>1c</b>) or V-shaped A₁-D-A₂-D-A₁ <b>(2a</b>–<b>2c</b>) oligothiophene chain structures of variable length were prepared; A₁, D, and A₂, represent dicyano-vinyl, oligothiophenyl, and <i>o</i>-carboranyl groups, respectively. Among this series, <b>2a</b> shows strong electron-acceptor capability of <i>o</i>-carborane comparable to that of the dicyano-vinyl substituent, which can be elaborated by a conformational effect driven by cage σ*−π* interaction. As a result, electronic communications between <i>o</i>-carborane and dicyano-vinyl groups are successfully achieved in <b>2a</b>

Phytochemical Investigation of Marker Compounds from Indigenous Korean <i>Salix</i> Species and Their Antimicrobial Effects

Salix species, including willow trees, are distributed in the temperate regions of Asian countries, including South Korea. Willow trees are used to treat pain and inflammatory diseases. Due to the medicinal properties of willow trees, pharmacological studies of other Salix spp. have gained attention; however, only a few studies have investigated the phytochemicals of these species. As part of our ongoing natural product research to identify bioactive phytochemicals and elucidate their chemical structures from natural resources, we investigated the marker compounds from indigenous Korean Salix species, namely, Salix triandra, S. chaenomeloides, S. gracilistyla, S. koriyanagi, S. koreensis, S. pseudolasiogyne, S. caprea, and S. rorida. The ethanolic extract of each Salix sp. was investigated using high-performance liquid chromatography combined with thin-layer chromatography and liquid chromatography–mass spectrometry-based analysis, and marker compounds of each Salix sp. were isolated. The chemical structures of the marker compounds (1–8), 3-(4-hydroxyphenyl)propyl β-D-glucopyranoside (1), 2-O-acetylsalicin (2), 1-O-p-coumaroyl glucoside (3), picein (4), isograndidentatin B (5), 2′-O-acetylsalicortin (6), dihydromyricetin (7), and salicin (8) were elucidated via nuclear magnetic resonance spectroscopy and high-resolution liquid chromatography–mass spectrometry using ultrahigh-performance liquid chromatography coupled with a G6545B Q-TOF MS system with a dual electrospray ionization source. The identified marker compounds 1–8 were examined for their antimicrobial effects against plant pathogenic fungi and bacteria. Dihydromyricetin (7) exhibited antibacterial activity against Staphylococcus aureus, inducing 32.4% inhibition at a final concentration of 125 μg/mL with an MIC50 value of 250 μg/mL. Overall, this study isolated the marker compounds of S. triandra, S. chaenomeloides, S. gracilistyla, S. koriyanagi, S. koreensis, S. pseudolasiogyne, S. caprea, and S. rorida and identified the anti-Staphylococcus aureus bacterial compound dihydromyricetin

Electronic Alteration on Oligothiophenes by <i>o</i>‑Carborane: Electron Acceptor Character of <i>o</i>‑Carborane in Oligothiophene Frameworks with Dicyano-Vinyl End-On Group

We studied electronic change in oligothiophenes by employing <i>o</i>-carborane into a molecular array in which one or both end(s) were substituted by electron-withdrawing dicyano-vinyl group(s). Depending on mono- or bis-substitution at the <i>o</i>-carborane, a series of linear A₁-D-A₂ (<b>1a</b>–<b>1c</b>) or V-shaped A₁-D-A₂-D-A₁ <b>(2a</b>–<b>2c</b>) oligothiophene chain structures of variable length were prepared; A₁, D, and A₂, represent dicyano-vinyl, oligothiophenyl, and <i>o</i>-carboranyl groups, respectively. Among this series, <b>2a</b> shows strong electron-acceptor capability of <i>o</i>-carborane comparable to that of the dicyano-vinyl substituent, which can be elaborated by a conformational effect driven by cage σ*−π* interaction. As a result, electronic communications between <i>o</i>-carborane and dicyano-vinyl groups are successfully achieved in <b>2a</b>