Growth development of children and adolescents with inflammatory bowel disease in the period 2000-2014 based on data of the Saxon pediatric IBD registry: a population-based study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in children is on the increase worldwide. Growth disorders are common in pediatric patients with inflammatory bowel disease. The aim of this paper is to investigate anthropometric indicators, including height and weight in children with inflammatory bowel disease in Saxony, one of the German federal states, and to evaluate growth trends in patients by comparing their height and weight with that of healthy children in Germany. METHODS: In Saxony, all children and adolescents with IBD were registered in the Saxon Pediatric IBD Registry from 2000 to 2014. The data used are therefore based on a total area-wide survey over 15 years. For this study, 421 datasets of children and adolescents aged 0-14 years with Crohn's disease (CD) (n = 291) or ulcerative colitis (UC) (n = 130) were analyzed. Z-score and percentile calculations were used to compare differences between IBD patients and the general population. RESULTS: The children with CD or UC (both sexes) had a significant lower weight at diagnosis (the mean weight z-score had negative values) versus the general population. The weight values lay mostly below P50 (the 50th percentile, median), more precisely, mostly between P10 and P50 of the body weight child growth curve for corresponding sexes (KiGGS 2003-2006). The height values of both sexes at diagnosis lay also mostly below P50 (the 50th percentile, median) of the child body growth curve for corresponding sexes (KiGGS 2003-2006), i.e. the mean height z-score was negative. But only the children with CD had a significant lower height, more precisely, mostly between P25 and P50 versus the general population (KIGGS). For children with UC the difference was not significant. CONCLUSION: In pediatric patients with IBD the possibility of growth disturbance, mainly in the form of weight retardation, is very probable.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

[Two new benzyl-benzoate glucosides from Plumeria rubra].

The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6″-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).

Guaiane-Type Sesquiterpenes from the Stems of Fissistigma oldhamii.

Two new guaiane-type sesquiterpenes dysodensiols J and L, one new natural product dysodensiol K together with four known biogenetically related guaiane-type sesquiterpenes were isolated from the stems of Fissistigma oldhamii. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR and Optical rotations data. Compound 1 contains an uncommon five-membered ether ring. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory activity with an IC50 value of 6.8 µM. Compounds 5-7 exhibited moderate inhibitory activity with IC50 values of 23.8, 26.6, and 27.1 µM, respectively.

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.

Three new long-chain polyenes from the mangrove-derived fungus Penicillium herquei JX4.

One new epimer pair of long-chain polyenes penicilqueis E (1) and F (2), and one new long-chain polyene pinophol G (3), along with one known compound (4), were obtained from EtOAc extract of the mangrove-derived fungus Penicillium herquei JX4. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The inhibitory activities of all compounds against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro were evaluated.

Zeylleucapenoids A-D, Highly Oxygenated Diterpenoids with Anti-Inflammatory Activity from Leucas zeylanica (L.) R. Br.

Four previously undescribed highly oxygenated diterpenoids (1-4), zeylleucapenoids A-D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily via NMR experiments. The absolute configuration of 1 was established using theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2-4 were assigned using theoretical ORD calculations. Zeylleucapenoids A-D were tested for anti-inflammatory activity against nitric oxide (NO) production in RAW264.7 macrophages, of which only 4 showed significant efficacy with an IC50 value of 38.45 µM. Further, active compound 4 was also evaluated for the inhibition of the release of pro-inflammatory cytokines TNF-α and IL-6 and was found to have a dose-dependent inhibitory effect, while it showed nontoxic activity for zebrafish embryos. A subsequent Western blotting experiment revealed that 4 inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated that the possible mechanism of action for 4 may be bind to targets via hydrogen and hydrophobic bond interactions.

Plumeriapropionics A-E, Carboxyl-Substituted Phenylpropionic Acid Derivatives with Anti-Inflammatory Activity from Plumeria rubra L.

Five rare carboxyl-substituted phenylpropionic acid derivatives, plumeriapropionics A-E (1-5), together with one known analog, cerberic acid B (6), were isolated from flowers of Plumeria rubra L. Their structures were elucidated using comprehensive spectroscopic methods. To date, only one compound of this structural type has been reported. The inhibitory activities of compounds 1-6 against nitric oxide (NO) production induced by lipopolysaccharide (LPS) were evaluated in vitro using mouse macrophage RAW264.7 cells. Compounds 1-6 showed remarkable inhibitory activities on NO production, with IC50 values in the range of 6.52 ± 0.23 to 35.68 ± 0.17 µM. These results indicate that the discovery of carboxyl-substituted phenylpropionic acid derivatives from the flowers of P. rubra, which show significant anti-inflammatory properties, could be of great importance for the research and development of novel natural anti-inflammatory agents.

Temporal changes in cyclinD-CDK4/CDK6 and cyclinE-CDK2 pathways: implications for the mechanism of deficient decidualization in an immune-based mouse model of unexplained recurrent spontaneous abortion.

BACKGROUND: Deficient endometrial decidualization has been associated with URSA. However, the underlying mechanism is poorly understood. This study aimed to investigate the temporal cytokine changes and the involvement of CyclinD-CDK4/6 and CyclinE-CDK2 pathways in the regulation of the G1 phase of the cell cycle during decidualization in a murine model of URSA. METHODS: Serum and decidual tissues of mice were collected from GD4 to GD8. The embryo resorption and abortion rates were observed on GD8 and the decidual tissue status was assessed. In addition, PRL, Cyclin D, CDK6, CDK4, Cyclin E, CDK2 expression in mice were measured. RESULTS: URSA mice showed high embryo resorption rate and PRL, Cyclin D, Cyclin E CDK2, CDK4, CDK6 down-regulation during decidualization. The hyperactivated Cyclin D-CDK4/CDK6 and cyclin E/CDK2 pathways inhibit the decidualization process and leading to deficient decidualization. CONCLUSION: Insufficient decidualization is an important mechanism of URSA. which is related to the decrease of Cyclin D、Cyclin E、 CDK2、CDK4 and CDK6 in decidualization process of URSA.

Biological Secondary Metabolites from the Lumnitzera littorea-Derived Fungus Penicillium oxalicum HLLG-13

Five new compounds, including two cyclopiane diterpenes conidiogenones J and K (1-2), a steroid andrastin H (5), an alkaloid (Z)-4-(5-acetoxy-N-hydroxy-3-methylpent-2-enamido) butanoate (6), and an aliphatic acid (Z)-5-acetoxy-3-methylpent-2-enoic acid (7), together with ten known compounds (3-4 and 8-15) were isolated from the EtOAc extract of the fermentation broth of the Lumnitzera littorea-derived fungus Penicillium oxalicum HLLG-13. Their structures were elucidated by 1D, 2D NMR, and HR-ESI-MS spectral analyses. The absolute configurations of 1, 2, 5, and 8 were determined by quantum chemical electronic circular dichroism (ECD) calculations, and the absolute configuration of 8 was determined for the first time. Compound 15 was a new natural product, and its NMR data were reported for the first time. Compounds 5 and 9-14 exhibited antibacterial activities against Staphylococcus epidermidis and Candida albicans, with MIC values ranging from 6.25 to 25 µg/ mL. Compounds 1-6 and 9-14 showed significant growth inhibition activities against newly hatched Helicoverpa armigera Hubner larvae, with IC50 values ranging from 50 to 200 µg/mL.

Sesquiterpenes from Fissistigma glaucescens inhibiting the proliferation of synoviocytes.

Two new sesquiterpenes, litseachrandaevanes C and D (1 and 2), together with five known sesquiterpenes (3 - 7), were isolated from the stems of Fissistigma glaucescens (Hance) Merr. Their structures were elucidated using comprehensive spectroscopic methods. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory effect on the proliferation of synoviocytes, with an IC50 value of 12.5 µM.

Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enones.

Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 µM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.

Five New Triene Derivatives from the Fungus Penicillium herquei JX4.

Five undescribed triene derivatives, pinophols B-F (2-6), together with one known compound, pinophol A (1), were obtained from the mangrove endophytic fungus Penicillium herquei JX4. The structures of compounds 1-6 were elucidated using IR, HR-ESI-MS, and NMR methods. The absolute configurations of compounds 1-6 were confirmed by comparing their experimental or calculated ECD spectra. Pinophols C and D (3 and 4) showed inhibitory activities against LPS-induced NO production.

Source apportionment of VOCs in a typical medium-sized city in North China Plain and implications on control policy.

Characteristics of atmospheric VOCs (volatile organic compounds) have been extensively studied in megacities in China, however, they are scarcely investigated in medium/small-sized cities in North China Plain (NCP). A comprehensive research on possible sources of VOCs was conducted in a medium-sized city of NCP, from May to September 2019. A total of 143 canister samples of 8 sites in Xuchang city were collected, and 57 VOC species were detected. The average VOC concentrations were 42.6 ± 31.6 µg/m3, with 53.7 ± 31.0 µg/m3 and 32.1 ± 27. 8 µg/m3, in the morning and afternoon, respectively. Alkenes and aromatics contributed 80% of the total ozone formation potential (OFP). Aromatics accounted for more than 95% of secondary organic aerosol potential (SOAP). VOCs were dominated by the local emission with significant transport from the southeast direction. PMF analysis extracted 6 sources, which were combustion (33.1%), LPG usage (19.3%), vehicular exhaust & fuel evaporation (15.8%), solvent usage (15.2%), industrial (9.11%) and biogenic (7.51%), respectively and they contributed 33.4%, 17.6%, 12.9%, 18.6%, 9.28% and 8.22% to the OFP, respectively. Combustion and LPG usage were the dominant VOC sources; and combustion, solvent usage and LPG usage were the main sources of OFP in Xuchang city, which were different to megacities in China with a high contribution from vehicular exhaust, solvent usage and industry, suggesting specific control strategies on VOCs need to be implemented in medium-sized city such as Xuchang city.

[Study on secondary metabolites of endophytic fungus Cladosporium sp. JJM22 hosted in Ceriops tagal].

Nine secondary metabolites(S)-5-hydroxy-4-methylchroman-2-one(1), 4-methoxynaphthalene-1,5-diol(2), 8-methoxynaphthalene-1,7-diol(3), 1,8-dimethoxynaphthalene(4),(2R,4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(5),(2R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-1-benzopyran-5-ol(6), 7-O-α-D-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one(7),(R)-3-methoxyl-1-(2,6-dihydroxyphenyl)-butan-1-one(8) and helicascolide A(9) were isolated from endophytic fungus Cladosporium sp. JJM22 by using column chromatographies of silica gel and ODS, and semi-preparative HPLC. Their structures were analyzed on the basis of spectroscopic and chemical data, especially NMR and MS. All isolated compounds were evaluated for their anti-inflammatory activities by examining the inhibitory activities on nitric oxide(NO) production induced by lipopolysaccharide in mouse macrophage RAW264.7 cells in vitro. Compounds 2-4 showed inhibitory activities.

The role of WNT1 mutant variant (WNT1c.677C>T ) in osteogenesis imperfecta.

Osteogenesis imperfecta (OI), also known as "brittle bone disease," is a rare inherited genetic disorder characterized by bone fragility and often associated with short stature. The mutation in WNT1 causes autosomal recessive OI (AR-OI) due to the key role of WNT/ß-catenin signaling in bone formation. WNT1 mutations cause phenotypes in OI of varying degrees of clinical severity, ranging from moderate to progressively deforming forms. The nucleotide change c.677C > T is one of the recurrent variants in the WNT1 alleles in Chinese AR-OI patients. To explore the effects of mutation c.677C > T on WNT1 function, we evaluated the activation of WNT/ß-catenin signaling, cell proliferation, osteoblast differentiation, and osteoclast differentiation in WNT1c.677C>T , WNT1c.884C>A , and wild type WNT1 transfected into MC3T3-E1 preosteoblasts. Plasmids containing wild type WNT1, WNT1c.677C>T , and WNT1c.884C>A cDNAs were constructed. Protein levels of phosphorylation at serine 9 of GSK-3ß (p-GSK-3ß), GSK-3ß, nonphosphorylated ß-catenin (non-p-ß-catenin), and ß-catenin were detected with western blot. Cell proliferation was determined using MTS. BMP-2 and RANKL mRNA and protein levels were detected by qPCR and western blot. Our results showed that WNT1c.677C>T failed to activate WNT/ß-catenin signaling and impaired the proliferation of preosteoblasts. Moreover, compared to wild type WNT1, WNT1c.677C>T downregulated BMP-2 protein expression and was exhibited a diminished capacity to suppress the RANKL protein level. In conclusion, mutation c.677C > T hindered the ability of WNT1 to induce the WNT/ß-catenin signaling pathway and it affected the WNT/ß-catenin pathway which might potentially contribute to hampered bone homeostasis.

Three new bioactive natural products from the fungus Talaromyces assiutensis JTY2.

A novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta C (3) together with four known itaconic acid derivatives (4-7) were isolated from the Talaromyces assiutensis JTY2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Among them, talarocyclopent (1) is the first represent an unusual type of cyclopentenone derivative, possessing a cyclopentenone unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. All isolated compounds were evaluated for their anti-inflammatory and antibacterial activities. Compounds 1-4 showed inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic bacteria.

Three new methylated Δ8-pregnene steroids from the Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2.

Three new methylated Δ8-pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 µg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 µg/mL. The discovery of three methylated Δ8-pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids.

3,4- seco-Norclerodane Diterpenoids from the Roots of Polyalthia laui.

Ten new clerodane diterpenoids, polylauioids A-J (1-10), and five known analogues (11-15) were isolated from the roots of Polyalthia laui. Among the new compounds, 3 and 8 are artifacts. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. The absolute configurations of 4, 5, and 7 were defined based on single-crystal X-ray diffraction and electronic circular dichroism data. Compounds 1 and 2 represent the first examples of rearranged 3,4- seco-norclerodane diterpenoids, and a putative biosynthesis pathway for these compounds is proposed. Compounds 1, 4, 6, 7, 9, and 10 showed anti-HIV activities with EC50 values ranging from 12.2 to 35.2 µM.