Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women

Background

The aim of this study was to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity.

Methods

We recruited 1179 people (aged 59.5?±?6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay. Serum FGF23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA?≥?80 cm².

Results

Serum OCN levels were inversely correlated with body fat parameters, while FGF23 and NGAL were positively correlated (P?<?0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P?<?0.05). The risk of visceral obesity significantly increased with higher FGF23 and/or NGAL levels, as well as with reduced OCN levels (all P?<?0.05). In addition, serum OCN, FGF23, and NGAL levels were independently associated with visceral obesity (all P?<?0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P?<?0.05).

Conclusions

Compared to the indicators of overall adiposity such as BMI or fat%, visceral adiposity indicators (W or VFA) were more closely related to serum OCN, FGF23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which revealed the independent relationship of endocrine function of skeleton with body fat.

     

Microbial virulence,molecular epidemiology and pathogenic factors of fluoroquinolone-resistant <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> infections in Guangzhou,China

Background

Fluoroquinolone-resistant Haemophilus influenzae (FRHI) has been reported worldwide but remain unclear in China.

Methods

A total of 402 H. influenzae isolates collected from 2016 to 2017 were included. Antimicrobial susceptibility on 10 antibiotics was performed, and minimum inhibitory concentration of ciprofloxacin- and nalidixic acid-resistant strains were further determined by E-test strips, with risk factors also evaluated. Strains with resistance or reduced susceptibility to ciprofloxacin were subjected to sequencing of the quinolone resistance-determining regions (QRDR) and plasmid-mediated quinolone resistance genes by sequencing, with multi-locus sequence typing.

Results

2.2% of H. influenzae strains were non-susceptible (7/402, 1.7%) or susceptible (2/402, 0.5%) to ciprofloxacin but NAL-resistant by E-test, and multidrug resistance was more common in fluoroquinolones non-susceptible H. influenzae group (p?=?0.000). Infection risk factors included invasive procedure (p?=?0.011), catching cold/previous contact with someone who had a cold (p?=?0.019), fluoroquinolones use during previous 3 months (p?=?0.003). With none of mutations obtained in gyrB, parE and other plasmid-mediated quinolone resistance genes, 7 and 4 strains were found for Ser-84-Leu substitutions in gyrA and one amino acid substitution in the QRDR of gyrA linked with one amino acid substitution in the QRDR of parC, respectively. In addition, five sequence types (ST) were identified, with ST1719 firstly found.

Conclusions

For the first time, this study has reported the incidence, risk factors, molecular determinants on fluoroquinolones resistance and ST of FRHI strains in mainland China, representing the first evidence of mutation of gyrA and parC in China and the new ST1719 worldwide.

     

Oxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis

Osteoarthritis (OA) is a common degenerative disease characterized by the progressive destruction both articular cartilage and the subchondral bone. The agents that can effectively suppress chondrocyte degradation and subchondral bone loss are crucial for the prevention and treatment of OA. Oxymatrine (OMT) is a natural compound with anti‐inflammatory and antitumour properties. We found that OMT exhibited a strong inhibitory effect on LPS‐induced chondrocyte inflammation and catabolism. To further support our results, fresh human cartilage explants were treated with LPS to establish an ex vivo degradation model, and the results revealed that OMT inhibited the catabolic events of LPS‐stimulated human cartilage and substantially attenuated the degradation of articular cartilage ex vivo. As subchondral bone remodelling is involved in OA progression, and osteoclasts are a unique cell type in bone resorption, we investigated the effects of OMT on osteoclastogenesis, and the results demonstrated that OMT suppresses RANKL‐induced osteoclastogenesis by suppressing the RANKL‐induced NFATc1 and c‐fos signalling pathway in vitro. Further, we found that the anti‐inflammatory and anti‐osteoclastic effects of oxymatrine are mediated via the inhibition of the NF‐κB and MAPK pathways. In animal studies, OMT suppressed the ACLT‐induced cartilage degradation, and TUNEL assays further confirmed the protective effect of OMT on chondrocyte apoptosis. MicroCT analysis revealed that OMT had an attenuating effect on ACLT‐induced subchondral bone loss in vivo. Taken together, these results show that OMT interferes with the vicious cycle associated with OA and may be a potential therapeutic agent for abnormal subchondral bone loss and cartilage degradation in osteoarthritis.     

The significance of the diversity and composition of the cecal microbiota of the Tibetan swine

The Tibetan swine (TIS) is a non-ruminant herbivore with high disease resistance. Also, it has the ability to digest plants with high fiber content. However, it is not known whether any relationship exist between these characteristics of the TIS and its cecal microbiota. Thus, this study aims to investigate the cecal microbiota of the adult TIS using high-throughput sequencing techniques in order to explore possible relationships between these unique characteristics of the TIS (high disease resistance and ability to digest high fiber plants) and its cecal microbiota. PIC pigs (lean type) were chosen as controls. The results show that 75,069 valid sequences of the 16S rRNA gene at V4-V5 region were obtained in the cecal content of TIS. They were composed of 15 phyla, 70 genera and divided into 660 Operational Taxonomic Units (OTUs). Bacteroidetes and Firmicutes were the predominant phyla in both breeds, but TIS had more Bacteroidetes than Firmicutes. Also, 42.4% of the cecal bacteria were found to be unclassified and uncultured. Many cellulolytic bacteria were also found in the two breeds. TIS (88.10%) had much higher abundance in the core bacterial communities than PIC pigs (81.29%), and the proportion of Bacteroides and Spirochaetes that can effectively degrade cellulose were 6.01 and 6.40% higher than PIC pigs, respectively, while Proteobacteria that are closely related to gastrointestinal diseases were 1.61% lower than PIC pigs. Thus, the disease resistance of the TIS and its ability to digest plants with high fiber content may be related to high abundance of core bacterial communities as well as the large number of unknown and unclassified bacteria.     

Triterpenes and Meroterpenes with Neuroprotective Effects from Ganoderma leucocontextum

Ganoderma leucocontextum is a well‐known medicinal mushroom cultivated in the Tibet Plateau of China. Chemistry investigation on the fruiting bodies of this mushroom resulted in the isolation of sixteen secondary metabolites including three new lanostane triterpenes, ganoleucoins Q – S ( 1 – 3 ), as well as thirteen known compounds ( 4 – 16 ). The structures of compounds 1 – 3 were determined by NMR, MS, CD spectral analysis, and chemical derivation method. The neuroprotective effects of compounds 1 – 16 were tested on PC12 cells. Compounds 1 and 2 showed protective effects against the H₂O₂ induced damage with the survival rate of 83.19 ± 0.92%, 73.37 ± 1.25% at the concentration of 200 μm , respectively. Meanwhile, compounds 1 and 2 induced neurite outgrowth at 50 – 200 μm . The results from this study suggested that G. leucocontextum and its metabolites may be potential functional food ingredients for the prevention of neurodegenerative diseases.     

Purification and characterization of a novel organic solvent-tolerant and cold-adapted lipase from Psychrobacter sp. ZY124

By screening 25 different psychrophilic strains isolated from the Arctic habitat, we isolated a strain capable of producing lipase. We identified this strain as Psychrobacter sp. ZY124 based on the amplified 16S rDNA sequence. The lipase, named as Lipase ZC12, produced from the supernatant of Psychrobacter sp. ZY124 cultured at 15 °C was purified to homogeneity by ammonium sulfate precipitation followed by Phenyl Sepharose FF gel hydrophobic chromatography. Based on the obtained amino acid sequence, Lipase ZC12 is classified as a member of the Proteus/psychrophilic subfamily of lipase family I.1; it has a molecular weight of 37.9 kDa. We also determined that the apparent optimum temperature for Lipase ZC12 activity is 40 °C. Lipase ZC12 shows remarkable organic solvent tolerance by remaining more 50% after incubated with 10–90% different organic solvents. In addition, acyl chain esters with C12 or longer were confirmed to be preferable substrates for Lipase ZC12. Lipase ZC12 also shows better stereoselectivity for (R, S)-1-phenylethanol chiral resolution in n-hexane solvent with (S)-1-phenylethanol (ee_p 92%) and conversion rate (39%) by transesterification reactions. These properties may provide potential applications in biocatalysis and biotransformation in non-aqueous media, such as in detergent, transesterification or esterification and chiral resolution.

     

Abstracts from the 2018 Respiratory Effectiveness Group Summit

Background

Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue.

Methods

The association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression.

Results

15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression.

Conclusion

This study is the first to validate a panel of CpG-sites that are associated with cigarette smoking and lung function levels in whole blood in the tissue of interest: lung tissue.

     

Efficient production of heat-stable antifungal factor through integrating statistical optimization with a two-stage temperature control strategy in <Emphasis Type="Italic">Lysobacter enzymogenes</Emphasis> OH11

Background

Heat-stable antifungal factor (HSAF) is a newly identified broad-spectrum antifungal antibiotic from the biocontrol agent Lysobacter enzymogenes and is regarded as a potential biological pesticide, due to its novel mode of action. However, the production level of HSAF is quite low, and little research has reported on the fermentation process involved, representing huge obstacles for large-scale industrial production.

Results

Medium capacity, culture temperature, and fermentation time were identified as the most significant factors affecting the production of HSAF and employed for further optimization through statistical methods. Based on the analysis of kinetic parameters at different temperatures, a novel two-stage temperature control strategy was developed to improve HSAF production, in which the temperature was increased to 32 °C during the first 12 h and then switched to 26 °C until the end of fermentation. Using this strategy, the maximum HSAF production reached 440.26?±?16.14 mg L^??1, increased by 9.93% than that of the best results from single-temperature fermentation. Moreover, the fermentation time was shortened from 58 h to 54 h, resulting in the enhancement of HSAF productivity (17.95%) and yield (9.93%).

Conclusions

This study provides a simple and efficient method for producing HSAF that could be feasibly applied to the industrial-scale production of HSAF.

     

<Emphasis Type="Italic">Streptomyces</Emphasis> sp. strain SK68, isolated from peanut rhizosphere,promotes growth and alleviates salt stress in tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis> cv. Micro-Tom)

A novel actinobacterium, strain SK68, was isolated from the rhizosphere of peanut plant and its salinity stress alleviation ability was studied using tomato (Solanum lycopersicum cv. Micro-Tom) plants. Based on 16S rDNA based phylogenetic analysis, strain SK68 has been identified as a Streptomyces sp. Strain SK68 had branched substrate mycelium bearing smooth surfaced spores and the spore colour is brownish grey on ISP4 medium. It exhibited enzyme activities such as xylanase, cellulase, amylase, and pectinase and degraded hypoxanthine, casein, and L-tyrosine. The strain SK68 differed in its banding pattern in BOX-PCR and RAPD fingerprinting compared to the closely matching type strains Streptomyces erythrochromogenes NBRC 3304^T (AB184746), S. flavotricini NBRC 12770^T (AB184132), S. racemochromogenes NBRC 12906^T (AB184235), and S. polychromogenes NBRC 13072^T (NR041109). Strain SK68 was evaluated for its salinity stress-alleviating activity in tomato plants with 180 mmol/L NaCl under gnotobiotic condition. A significant increase in plant biomass was observed in strain SK68-inoculated tomato plants under salt stress compared to control and salt-stressed non-inoculated plants.     

Rational Architecture Design Enables Superior Na Storage in Greener NASICON‐Na4MnV(PO4)3 Cathode

Na₃V₂(PO₄)₃ has attracted great attention due to its high energy density and stable structure. However, in order to boost its application, the discharge potential of 3.3–3.4 V (vs Na⁺/Na) still needs to be improved and substitution of vanadium with other lower cost and earth‐abundant active redox elements is imperative. Therefore, the Na superionic conductor (NASICON)‐structured Na₄MnV(PO₄)₃ seems to be more attractive due to its lower toxicity and higher voltage platform resulting from the partial substitution of V with Mn. However, Na₄MnV(PO₄)₃ still suffers from poor electronic conductivity, leading to unsatisfactory capacity delivering and poor high‐rate capability. In this work, a graphene aerogel–supported in situ carbon–coated Na₄MnV(PO₄)₃ material is synthesized through a feasible solution‐route method. The elaborately designed Na₄MnV(PO₄)₃ can reach ≈380 Wh kg^?1 at 0.5 C (1 C = 110 mAh g^?1) and realize superior high‐rate capability evenat 50 C (60.1 mAh g^?1) with a long cycle‐life of 4000 cycles at 20 C. This impressive progress should be ascribed to the multifunctional 3D carbon framework and the distinctive structure of trigonal Na₄MnV(PO₄)₃, which are deeply investigated by both experiments and calculations.