A neoclerodane orthoester and other new neoclerodane diterpenoids from Teucrium yemense chemistry and effect on secretion of insulin

Teucrium yemense, a medicinal plant commonly grown in Saudi Arabia and Yemen, is traditionally used to treat infections, kidney diseases, rheumatism, and diabetes. Extraction of the dried aerial parts of the plant with methanol, followed by further extraction with butanol and chromatography, gave twenty novel neoclerodanes. Their structures, relative confgurations and some conformations were determined by MS and 1-D and 2-D NMR techniques. Most were fairly conventional but one contained an unusual stable orthoester, one had its (C-16)–(C-13)–(C-14)–(C-15) (tetrahydro)furan unit present as a succinic anhydride and one had a rearranged carbon skeleton resulting from ring-contraction to give a central octahydroindene bicyclic core, rather than the usual decalin. Mechanisms are proposed for the biosynthetic formation of the orthoester and for the ring-contraction. Four novel neoclerodanes increased the glucose-triggered release of insulin from isolated murine pancreatic islets by more than the standard drug tolbutamide, showing that they are potential leads for the development of new anti-diabetic drugs

Stimulation of insulin secretion by 5-methylcoumarins and its sulfur analogues isolated from Clutia lanceolata Forssk

Clutia lanceolata Forssk. (C. lanceolata) is a medicinal plant native to sub-Saharan Africa and the Arabian Peninsula. Phytochemical investigation of the aerial parts of C. lanceolata yielded twenty-one coumarins including methylthio and methylsulfinyl-coumarins. Thirteen of these compounds are reported here for the first time, named as cluteolin A to M. The remaining eight compounds are known but have not been associated previously with C. lanceolata. The structures of the undescribed compounds were elucidated from their 2D NMR and MS spectra. Single crystal X-ray analyses confirmed the structures of eleven compounds. As, in Saudi Arabian tradition, C. lanceolata has been reported to have anti-diabetic and anti-fungal properties, the coumarins were examined for their biological activity. Seven compounds strongly enhanced the glucose-triggered release of insulin by murine pancreatic islets, with two compounds showing more than two-fold enhancement of insulin secretion, compared with the standard drug glimepiride

Three allele combinations associated with Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. METHODS: 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. RESULTS: We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. CONCLUSION: These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles

Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer

Colon tumors from four independent mouse models and 100 human colorectal cancers all exhibited striking recapitulation of embryonic colon gene expression from embryonic days 13.5-18.5

VALIDITY AND RELIABILITY OF COMMONLY USED SELF-REPORT PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR INSTRUMENTS AMONG COLLEGE STUDENTS

BACKGROUND: Self-report instruments are commonly used to assess physical activity (PA) and sedentary behavior (SED) among college students, yet limited evidence exists comparing instruments to determine which provide the most valid and reliable estimates in this cohort. The purpose of this study was to assess the validity and reliability of several commonly used self-report PA and SED instruments among college students. METHODS: Students (n=98; 70% female; 19.8±1.4 yrs) completed the Global Physical Activity Questionnaire (GPAQ), International Physical Activity Questionnaire-Long Form (IPAQ-L) and Short Form (IPAQ-S), Godin Leisure Time Exercise Questionnaire (GLTEQ), Sedentary Behavior Questionnaire (SBQ), and SIT-Q on 2 occasions separated by 7-8 days. Participants wore devices at the waist (ActiGraph GT9X Link) and on the thigh (activPAL3) to objectively assess PA and SED, respectively, over the 7-8 days between administrations of the self-report instruments. Intraclass correlation coefficients were calculated to assess test-retest reliability. Concurrent validity was assessed using Spearman’s rho to compare responses from the second administration of the instruments to the associated variables from the devices. Mean absolute error (MAE) was calculated for variables from self-report instruments using the devices as the comparison. RESULTS: For total PA (METmin/wk), reliability was highest for IPAQ-L and IPAQ-S (both ICC=0.63). IPAQ-S showed the highest reliability for moderate- to vigorous PA (ICC=0.74). Reliability for SED was highest from the SBQ (ICC=0.83). For MVPA, validity was highest for GPAQ (ρ=0.390) and lowest for IPAQ-L (ρ=0.256). For SED, validity was highest for IPAQ-L (ρ=0.284) and lowest for SBQ (ρ=-0.149). MAE for MVPA and SED was lowest for IPAQ-L (208.4 min and 1.9 hr, respectively). CONLUSIONS: Overall, reliability was moderate to good and validity was poor for the self-report instruments, which aligns with results from previous investigations in general adult populations. Researchers seeking to assess PA and SED among college students should be aware of the differences in reliability and validity among the most commonly used self-report instruments. It is suggested that researchers determine the most important outcomes for their specific research question (e.g., total PA, MVPA, etc.) and select an instrument that will provide the highest level of validity and reliability for those metrics