A Molecular Cage Accessed by Threefold Click Reaction of a C3v-Symmetric Triazido-Functionalized Tribenzotriquinacene.

The hitherto unknown hexakis(halomethyl)-functionalized tribenzotriquinacenes (TBTQs) 9 and 10 were synthesized from the key 4b,8b,12b-tribromo-TBTQ derivative 6 by an improved route in 67% overall yield. Extension of the bowl-shaped framework of 9 or 10 by threefold condensation with propargylamine or 2-azidoethylamine afforded the corresponding TBTQ-trialkyne 11 and TBTQ-triazide 12, respectively. While attempts to construct bis-TBTQ cages, including homodimerization of 11 and heterocoupling of 11 with 12, were unsuccessful, triazide 12 was found to undergo threefold [3 + 2]-cycloaddition with 3-ethynylaniline and phloroglucinol tripropargyl ether under click chemistry conditions. The latter reaction enabled facile capping of the TBTQ bowl to give the novel cage compound 5 in 22% yield.

Purification and characterization of a novel low-molecular-weight antimicrobial peptide produced by Lactiplantibacillus plantarum NMGL2.

The present study aimed to purify and characterize a novel low-molecular-weight antimicrobial peptide (AMP) named as PNMGL2 produced by Lactiplantibacillus plantarum NMGL2. The AMP was effectively separated and purified by ethyl acetate extraction and DEAE-Sepharose anion exchange chromatography. Tricine-SDS-PAGE of the purified AMP showed a major protein band below 1.7 kDa, which was identified by MALDI-TOF MS to be a hexapeptide LNFLKK (761.95 Da), and structurally characterized to be combination of helixes and random coil by a PEP-FOLD 3 De novo approach. The antimicrobial activity of LNFLKK was confirmed by chemical synthesis of the peptide that showed clear inhibition (MIC 7.8 mg/mL) against both Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes), and Gram-negative bacteria (Enterobacter sakazakii, Escherichia coli and Shigella flexneri). PNMGL2 was pH resistant (pH 2-9), heat stable (121 °C, 30 min), and protease sensitive. Treatment of UV rays, sodium chloride and organic solvents did not decrease the activity. Sequencing of the whole genome of L. plantarum NMGL2 revealed presence of a bacteriocin gene cluster with two putative bacteriocin genes (ORF4 and ORF5) that were not expressed, confirming the significance of PNMGL2 contributing the antimicrobial activity of the strain. This study demonstrated the low-molecular-weight AMP that was uncharacterized in the relevant available databases, suggesting its potential application as a novel natural food preservative.

Synthesis of Enantiopure Hydrocarbon Cages Based on an Optically Resolved C3-Symmetric Triaminotribenzotriquinacene.

The synthesis of the enantiomerically pure, D3-symmetric covalent hydrocarbon cages (+)-(M,M)-4 and (-)-(P,P)-4 bearing two C3-symmetrically functionalized tribenzobenzotriquinacene (TBTQ) vertices is reported. The enantiomerically pure TBTQ building blocks (+)-(M)-5 and (-)-(P)-5 were prepared via the diastereomeric TBTQ triamides obtained by use of both Boc-d- and Boc-l-phenylglycine as chiral auxiliaries.

Long non-coding RNA HCG11 sponging miR-522-3p inhibits the tumorigenesis of non-small cell lung cancer by upregulating SOCS5.

BACKGROUND: Numerous studies have shown that long non-coding RNA (lncRNA) is involved in various human diseases including non-small cell lung cancer (NSCLC). The aim of this study was to explore the potential role of lncRNA HCG11 in the pathogenesis of NSCLC. METHODS: The mRNA expression of HCG11, miR-522-3p and SOCS5 was detected by RT-qPCR. The regulatory mechanism of lncRNA HCG11 was investigated by CCK-8, transwell and dual luciferase reporter assays. RESULTS: Downregulation of lncRNA HCG11 and upregulation of miR-522-3p were found in NSCLC tissues and cells, and abnormal expressions of lncRNA HCG11 and miR-522-3p were related to adverse clinical outcomes of NSCLC patients. LncRNA HCG11 acted as a molecular sponge for miR-522-3p. Functionally, lncRNA HCG11 inhibited cell viability, migration and invasion in NSCLC by downregulating miR-522-3p. Further, miR-522-3p directly targeted SOCS5. lncRNA HCG11 could positively regulate SOCS5 expression in NSCLC. In addition, HCG11 downregulation or miR-522-3p overexpression abolished the inhibitory effect of SOCS5 on cell viability, migration and invasion in NSCLC. CONCLUSIONS: LncRNA HCG11 inhibits cell viability, migration and invasion in NSCLC by functioning as a ceRNA of miR-522-3p to upregulate SOCS5.

A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population.

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case-control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05-1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03-1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m2 , adjusted OR = 1.34, 95% CI = 1.12-1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m2 , adjusted OR = 1.02 , 95% CI = 0.86-1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.

miR-211 inhibits proliferation, invasion and migration of cervical cancer via targeting SPARC.

Cervical cancer remains one of the most frequent gynecological malignancies among females around the world. Therefore, fully understanding the molecular mechanisms underlying the progression of cervical cancer may be critical for the development of effective therapeutic strategies against cervical cancer. The object was to evaluate the potential effect of miR-211 and verify its influence on the function of secreted protein acidic and rich in cysteine (SPARC) in cervical cancer. It was demonstrated that miR-211 was downregulated in cervical cancer cell lines (HeLa and C33A) and cervical cancer specimens, while SPARC expression level was higher in tumor tissues. We also revealed miR-211 upregulated expression could inhibit cells proliferation, migration and invasion in vivo. SPARC was confirmed as a direct and functional target of miR-211 and the inverse relationship between them was also observed. The results of the present study suggest that miR-211 reduced cancer growth, migration and invasion, and suppresses the SPARC expression in cervical cancer. This newly identified miR-211 may provide further insight into the progression and offers a promising target for cervical cancer therapy.