The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

Discovery and Biomimetic Semisynthesis of Spirophyllines A-D from Uncaria rhynchophylla.

Spirophyllines A-D (1-4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3'-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1-8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 µM).

Development and structure-activity relationships of tanshinones as selective 11ß-hydroxysteroid dehydrogenase 1 inhibitors.

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) represents a promising drug target for metabolic syndrome, including obesity and type 2 diabetes. Our initial screen of a collection of natural products from Danshen led to the identification of tanshinones as the potent and selective 11ß-HSD1 inhibitors. To improve the druggability and explore the structure-activity relationships (SARs), more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials. More than 10 derivatives exhibited potent in vitro 11ß-HSD1 inhibitory activity and good selectivity over 11ß-HSD2 across human and mouse species. Based on the biological results, SARs were further discussed, which was also partially rationalized by a molecular docking model of 1 bound to the 11ß-HSD1. Remarkably, compounds 1, 17 and 30 significantly inhibited 11ß-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice, which merits further investigations as anti-diabetic agents. This study not only provides a series of novel selective 11ß-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes, but also expands the boundaries of the chemical and biological spaces of tanshinones.

Eleven undescribed alkaloids from the rhizomes of Sinomenium acutum and their IDO1 and TDO inhibitory activities.

Eleven previously undescribed alkaloids, named sinometumines A-K, along with three known alkaloids, were isolated from the rhizomes of Sinomenium acutum. The chemical structures of these unreported compounds were established using extensive spectroscopic methods (IR, UV, HRESIMS, and NMR), and their absolute configurations were determined by single crystal X-ray diffraction analyses and calculated electronic circular dichroism spectroscopy (ECD). Sinometumine D was the first aporphine-type derived alkaloid inner salt with a rearranged dibenzofuran ring backbone. Sinometumine E was a rare protoberberine-type alkaloid with a complex 6/6/6/6/6/6 hexacyclic skeleton. This was the first report of alkaloids with these two skeletons isolated from S. acutum. All isolates were evaluated for their inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). Lysicamine possessed noteworthy inhibitory activities as an IDO1/TDO dual inhibitor with IC50 values of 6.22 ± 0.26 µM and 23.76 ± 2.93 µM, respectively, and liriodenine revealed moderate dual inhibition with IC50 values of 31.65 ± 4.44 µM and 15.64 ± 0.26 µM. The intermolecular interactions and binding modes between lysicamine and IDO1/TDO were elaborated by molecular docking studies.

Spiroligustolides A and B: Two pairs of enantiomeric spiro-orthoester-containing phthalide dimers as Cav3.1 calcium channel inhibitors from Ligusticum Chuanxiong Hort.

Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A (1a/1b) and B (2a/2b), featuring a unique spiroorthoster linkage between two monomeric units to form a 5/6/5/6/6-fused ring system, were isolated from the roots of Ligusticum chuanxiong. The structures and relative configurations of 1 and 2 were determined by HR-ESI-MS, IR, and NMR spectroscopic data, coupled with single-crystal X-ray diffraction analysis, and the absolute configurations of 1a, 1b, 2a, and 2b were established by comparing the experimental and calculated electronic circular dichroism (ECD) data. Plausible biosynthetic pathway for 1 and 2 was proposed. Moreover, compounds 1, 1b, and 2b showed remarkable inhibitory activities on Cav3.1 calcium channel with IC50 values of 8.34, 7.08, and 8.60 µM, respectively.

seco-Prezizanne Sesquiterpenes and Prenylated C6-C3 Compounds from the Fruits of Illicium lanceolatum A. C. Smith.

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.

Rhynchines A-E: Cav3.1 Calcium Channel Blockers from Uncaria rhynchophylla.

Rhynchines A-E (1-5), five new indole alkaloids with an unprecedented skeleton, were isolated from Uncaria rhynchophylla. The new skeleton was characterized by an indole moiety and a 2-oxa-8-azatricyclo[6,5,01,5,01,8]tridecane core, forming a unique 6/5/7/5/5 ring system. Their structures were determined by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, infrared spectroscopy, and calculated electronic circular dichroism (ECD) and were confirmed by X-ray crystallography. Interestingly, 1 and 2 showed strong inhibitory activities against the Cav3.1 calcium channel with IC50 values of 6.86 and 10.41 µM.

Network Analyses of the Differential Expression of Heat Shock Proteins in Glioma.

Heat shock protein (HSP) is a family of highly conserved protein, which exists widely in various organisms and has a variety of important physiological functions. Currently, there is no systematic analysis of HSPs in human glioma. The aim of this study was to investigate the characteristics of HSPs through constructing protein-protein interaction network (PPIN) considering the expression level of HSPs in glioma. After the identification of the differentially expressed HSPs in glioma tissues, a specific PPIN was constructed and found that there were many interactions between the differentially expressed HSPs in glioma. Subcellular localization analysis shows that HSPs and their interacting proteins distribute from the cell membrane to the nucleus in a multilayer structure. By functional enrichment analysis, gene ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, the potential function of HSPs and two meaningful enrichment pathways was revealed. In addition, nine HSPs (DNAJA4, DNAJC6, DNAJC12, HSPA6, HSP90B1, DNAJB1, DNAJB6, DNAJC10, and SERPINH1) are prognostic markers for human brain glioma. These analyses provide a full view of HSPs about their expression, biological process, as well as clinical significance in glioma.