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Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. Loss of insulin sensitivity disrupts glucose homeostasis and elevates the risk of developing the metabolic syndrome that includes Type 2 diabetes. This study assesses the effect on subcritical-water extract of Gracilaria chorda(GC) at 210 °C (GCSW210) in IR induction models of high glucose (HG)-induced zebrafish larvae and dexamethasone (DEX)-induced L6 myotubes.

The histogenesis of pleomorphic adenoma (PA) of the salivary glands remains controversial. PAs are characterized by the transition of epithelial cells to spindled mesenchymal cells, known as epithelial-mesenchymal transition (EMT). The present study aimed to identify a major EMT-inducing transcription factor (EMT-TF) in PAs. Real-time PCR analysis of SNAIL, SLUG, ZEB1, and TWIST1demonstrated that only SLUGwas significantly upregulated in normal salivary glands and PAs. Combined in situ hybridization for SLUGand multiplex immunohistochemistry for CK19 and P63 revealed that SLUGwas specifically expressed in the myoepithelial cells of normal salivary glands. In PAs, SLUGwas expressed in neoplastic myoepithelial cells and stromal cells but not in the luminal cells lining the inner layers of tumor glands. SLUGexpression showed no correlation with PLAG1expression, and in vitro experiments demonstrated that PLAG1suppression in primary cultured PA cells or PLAG1overexpression in HEK 293 T cells did not affect SLUGlevels, indicating that PLAG1was not involved in the upregulation of SLUGin PAs. The suppression of SLUGexpression in cultured PA cells resulted in a morphology change to a less elongated shape and attenuated tumor growth. In addition, SLUGdownregulation led to increased E-cadherin and decreased N-cadherin and vimentin expression levels along with decreased migratory activity in cultured PA cells. These findings suggest that SLUGis a major TF that can induce EMT in PAs. In summary, SLUG is specifically and highly expressed in the myoepithelial cells and stromal cells of PAs and is a key regulator of EMT in PAs.

The histogenesis of pleomorphic adenoma (PA) of the salivary glands remains controversial. PAs are characterized by the transition of epithelial cells to spindled mesenchymal cells, known as epithelial-mesenchymal transition (EMT). The present study aimed to identify a major EMT-inducing transcription factor (EMT-TF) in PAs. Real-time PCR analysis of SNAIL, SLUG, ZEB1, and TWIST1demonstrated that only SLUGwas significantly upregulated in normal salivary glands and PAs. Combined in situ hybridization for SLUGand multiplex immunohistochemistry for CK19 and P63 revealed that SLUGwas specifically expressed in the myoepithelial cells of normal salivary glands. In PAs, SLUGwas expressed in neoplastic myoepithelial cells and stromal cells but not in the luminal cells lining the inner layers of tumor glands. SLUGexpression showed no correlation with PLAG1expression, and in vitro experiments demonstrated that PLAG1suppression in primary cultured PA cells or PLAG1overexpression in HEK 293 T cells did not affect SLUGlevels, indicating that PLAG1was not involved in the upregulation of SLUGin PAs. The suppression of SLUGexpression in cultured PA cells resulted in a morphology change to a less elongated shape and attenuated tumor growth. In addition, SLUGdownregulation led to increased E-cadherin and decreased N-cadherin and vimentin expression levels along with decreased migratory activity in cultured PA cells. These findings suggest that SLUGis a major TF that can induce EMT in PAs. In summary, SLUG is specifically and highly expressed in the myoepithelial cells and stromal cells of PAs and is a key regulator of EMT in PAs.

Despite the continuing global crisis caused by coronavirus disease 2019 (COVID‐19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2‐benzylaminoquinazolin‐4(3H)‐one derivatives and demonstrated that they are effective against SARS‐CoV‐2. Among the synthesized derivatives, 7‐chloro‐2‐(((4‐chlorophenyl)(phenyl)methyl)amino)quinazolin‐4(3H)‐one (Compound 39) showed highest anti‐SARS‐CoV‐2 activity, with a half‐maximal inhibitory concentration value greater than that of remdesivir (IC50= 4.2 μM vs. 7.6 μM, respectively), which gained urgent approval from the U.S. Food and Drug Administration. In addition, Compound 39showed good results in various assays measuring metabolic stability, human ether a‐go‐go, Cytochromes P450 (CYPs) inhibition, and plasma protein binding (PPB), and showed better solubility and pharmacokinetics than our previous work. Lead optimization of 2‐benzylaminoquinazolin‐4(3H)‐one derivatives

Study on the 2‐phenylchroman‐4‐one derivatives and their anti‐MERS‐CoVactivities.

In a previous study, we showed that several octahydroindene derivatives are potent protease activated receptor 1 (PAR1) antagonists. In the current study, we prepared a series of trans‐fused 5,5‐difulorooctahydroindenes which do not have a C5 stereogenic center, and evaluated their biological activities and metabolic stabilities. Compound 19in this series, containing a spirooxazolidinone moiety at C2, showed excellent efficacy in both PAR1 binding (IC50= 70 nM) and human platelet rich plasma (PRP) aggregation (IC50= 0.19 μM), along with good metabolic stability (R50= 345.8, 337.2, and 43.4 min in human, rat, and monkey liver microsomes, each), which is comparable to that of vorapaxar. Four stereoisomers of 19were prepared and evaluated. (1S,2R,3aR,7aR)‐5,5‐Difluoro‐1‐[(E)‐2‐[5‐(3‐fluorophenyl)pyridin‐2‐yl]vinyl]octahydrospiro(indene‐2,5′‐oxazolidin)‐2′‐one (31) was found to be the most active (IC50= 21 nM) stereoisomer as PAR1 antagonist. Compound 31exhibited good in vivooral PK profiles and significant ex vivoantithrombotic efficacy in cynomolgus monkeys upon oral administration. When the plasma concentration of 31was maintained above 200 ng/mL, platelet aggregation induced by haTRAP was completely inhibited. Inhibitory activity on PAR1 binding.

Maternal embryonic leucine zipper kinase (MELK) has been implicated in various cellular processes and is highly upregulated in diverse cancers, then it is thought to be a promising anticancer target. 3-Anilino-1H-pyrazolo[3,4-b]pyridine scaffold was identified as a novel scaffold for MELKkinase inhibitors in high throughput screening (HTS). From exploration for structure–activity relationship (SAR) studies mainly by the modification of the 3 (C3), and 5-positions (C5), 4-(4-methylpiperazin-1-yl)-N-{5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrazolo[3,4-b]pyridin-3-yl}benzamide (21a) was found to exhibit good activity (IC50?=?0.15?µM) on MELKas a lead in early state.

Crateva unilocularisBuch-Ham has traditionally been used in Nepal for the treatment and prevention of diabetes. However, scientific verification through studies on the preventive effect of C. unilocularison diabetes has not been done properly. In this study we investigated the effect of C. unilocularisleaf extract (CULE) on glucose uptake and insulin resistance. The effect of CULE on glucose uptake in an in vivo system was measured using zebrafish. In the cell-free system, enzymes activities related to diabetes were measured. Moreover, in the cell-cultured system, RIN-m5F pancreatic beta cells, 3T3-L1 adipocytes, and L6 myotubes were used to measure the effect of CULE on insulin secretion and glucose metabolism. CULE effectively enhanced glucose uptake in zebrafish larvae, and inhibited the activity of dipeptidyl peptidase-IV (DPP-IV) and protein tyrosine phosphatase-1B (PTP-1B) enzymes related to insulin secretion and insulin signaling activation. Also, CULE significantly increased insulin secretion with suppression of NO production in RIN-m5F pancreatic beta cells. In L6 myotubes and TNF-α-induced insulin resistance model of 3T3-L1 adipocytes, CULE significantly increased glucose uptake and immunofluorescence staining of glucose transporter (GLUT)4 protein. Furthermore, the regulatory response of glucose metabolism by CULE was a close correlation with the activation of insulin signaling (IRβ, PI3K, AKT) and 5′-AMP-activated protein kinase (AMPK)α and the reduction of p38 mitogen-activated protein kinase (MAPK) in TNF-α-induced insulin resistance model of 3T3-L1 adipocytes. Thus, our results suggest that CULE may act as a potential agent for the prevention and treatment of metabolic syndrome associated with type 2 diabetes.

Carbohydrate antigen 19–9 (CA 19–9) can be increased in benign ovarian cysts, but extreme elevation is rare.

If the surface of the titanium chips (TC) was modified by thermal treatment under air atmosphere, it could be reused as catalyst support or photocatalytic materials. TC-supported CuO and ZnO catalysts were prepared by impregnation (IMP) method and co-precipitation (CP) method using cupric nitrate and zinc nitrate solution as precursors. Loading of CuO and ZnO on TC was 40.6wt% and 50.3wt%, respectively. The catalytic activity for CO2 hydrogenation was investigated using a flow-typed reactor under various pressures. Conversion of carbon dioxide to methyl alcohol over the CuO-ZnO/TC catalyst by CP and IMP methods were ca. 22% and ca. 10%, respectively. Conversion of carbon dioxide over CuO-ZnO/TC catalyst by CP method was increased with increasing reaction temperature in ranging of 15atm to 30 atm. Maximum selectivity and yield to methyl alcohol over CuO-ZnO/TC catalyst at 250℃ were ca. 90% at 20 atm and ca. 18.2% at 30 atm, respectively.

Pure and simple: A simple chimeric PNA (named chiPNA) was observed to selectively bind RNA in a 1:1 mixture of RNA and DNA with identical base sequences. This binding was assessed by chip‐based assay.

The previously developed enantioselective iodocyclization of γ‐hydroxy‐cis‐alkenes required 30 mol % of (R,R)‐salen–CoIIcomplex as chiral catalyst and 0.75 equivalent of N‐chlorosuccinimide (NCS) as activator to produce 2‐substituted tetrahydrofurans with 61 to 90 % ee. Due to the considerable loading amount of the CoIIcomplex, another more effective catalyst was pursued by screening (R,R)‐salen–transition metal complexes. When 10 mol % of the catalysts were applied with 0.5 equivalent of NCS, a higher level of stereoselectivity was attained with the corresponding CrIIICl (84 % ee), MnIICl (52 % ee) and CoIIcomplexes (66 % ee). Refinement of the conditions established a novel catalytic enantioselective iodocyclization protocol using iodine in the presence of 7 mol % of (R,R)‐salen–CrIIICl complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93 % ee.

Asymmetric iodocyclization and mercuriocyclization of γ-hydroxy-cis-alkenes have been established. The iodocyclization has been attained with 1.2 equiv of iodine in the presence of the catalyst system prepared from 0.3 equiv of (R,R)-salen−Co(II) complex and 0.75 equiv of NCS to produce 2-substituted tetrahydrofurans with up to 90% ee. The mercuriocyclization has been achieved using 1.2 equiv of Hg(II) complexed with 4-(2-naphthyl)bisoxazoline (1:1 complex) in the presence of 5 equiv of K2CO3and 10 equiv of MeOH to procure 2-substituted tetrahydrofurans with up to 95 % ee.

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Struma ovarii (SO) is a rare ovarian mature teratoma which is composed of 50% or more thyroid tissues. Malignant transformation is reported to occur in less than 5% of all cases, and it leads to 5–6% metastatic disease. The most common type is a papillary carcinoma. However, follicular carcinoma of arising from SO is extremely rare.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.