Therapeutic Role of Fibroblast Growth Factor 21 (FGF21) in the Amelioration of Chronic Diseases

International Journal of Peptide Research and Therapeutics - Fibroblast growth factor-21 (FGF21) is a member of the family of fibroblast growth factors (FGFs). FGF21 (synthesized by many organs)...     

Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate

Virologica Sinica - Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue...     

AZD8835 inhibits osteoclastogenesis and periodontitis-induced alveolar bone loss in rats

Chronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide-3-kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (Trap), cathepsin K (Ctsk), V-ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)-induced PI3K/protein kinase B (AKT), extracellular signal-regulated kinase, and nuclear factor-κB signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.     

Genetic association analysis using sibship data: a multilevel model approach

Family based association study (FBAS) has the advantages of controlling for population stratification and testing for linkage and association simultaneously. We propose a retrospective multilevel model (rMLM) approach to analyze sibship data by using genotypic information as the dependent variable. Simulated data sets were generated using the simulation of linkage and association (SIMLA) program. We compared rMLM to sib transmission/disequilibrium test (S-TDT), sibling disequilibrium test (SDT), conditional logistic regression (CLR) and generalized estimation equations (GEE) on the measures of power, type I error, estimation bias and standard error. The results indicated that rMLM was a valid test of association in the presence of linkage using sibship data. The advantages of rMLM became more evident when the data contained concordant sibships. Compared to GEE, rMLM had less underestimated odds ratio (OR). Our results support the application of rMLM to detect gene-disease associations using sibship data. However, the risk of increasing type I error rate should be cautioned when there is association without linkage between the disease locus and the genotyped marker.     

A novel dichloromethane-degrading <Emphasis Type="Italic">Lysinibacillus sphaericus</Emphasis> strain wh22 and its degradative plasmid

Dichloromethane (DCM)-degrading bacterium strain wh22 (GenBank accession number FJ418643) was isolated and identified as Lysinibacillus sphaericus based on standard morphological and physiological properties, cellular fatty acid composition, mole percent guanine–cytosine content, and nucleotide sequence analysis of enzymatically amplified 16S ribosomal deoxyribonucleic acid. The strain also grew on many other halocarbons found in the waste gases of industrial effluents, such as 1,2-dichloroethane, chlorobromomethane, methylene bromide, 1,1,1-trichloroethane, trichloroethylene, and hexachlorobenzene. The strain harbored a novel degradative plasmid, pRC11 (48.8 kb). The genes coding for the metabolism of DCM were found to be plasmid-borne, and a physical map of the plasmid has been established. The purified plasmid was transformed to dcm ⁻ Escherichia coli DH5 at a rate of 1.65 × 10⁵. The transformed cells were able to grow on DCM at a concentration of 5–16 mM and can be further used as an excellent source for genetic manipulations leading to the construction of genetically modified microbial strains or genetically engineered microorganisms.     

HIV Prevalence and Associated Factors among Foreign Brides from Burma in Yunnan Province,China

Background

Many Burmese women have migrated to Yunnan Province and married local residents over the past few decades; however, limited information is available on their HIV prevalence and ability to cope with HIV. This study aims to assess the prevalence of HIV and knowledge related to AIDS, as well as to discover possible risk factors of HIV infection among foreign brides from Burma in Yunnan Province.

Methods

A cross-sectional study was taken of all Burmese cross-border wives residing in Tengchong County using standardized questionnaires. HIV and syphilis testing was conducted at the same time.

Results

Among 600 Burmese brides, the HIV prevalence was 2.17%. Those aged 21–30, those with higher education levels and those who had resided in China less than one year had higher infection rates. The AIDS awareness rate of 39.50% was very low in this population. Only 28.67% of participants had ever been involved in prevention services. The rate of condom use was low. Classification by age, education, occupation, prior HIV testing and prior use of HIV prevention services showed a statistically significant association with mean knowledge score (p<0.05). Residing in China less than one year (OR = 3.86, 95% CI = 1.09–13.70) and having casual sex in the last year (OR = 10.49, 95% CI = 1.20–91.59) were risk factors for HIV infection.

Conclusions

Burmese brides in China are not only exposed to a high risk of HIV infection, but also seriously lack response capabilities. Educational interventions and control efforts are practical approaches that need to be strengthened among this population.     

黑麦染色体银染的初步研究

本文对黑麦染色体的银染条件进行了探索,并对黑麦染色体上银染正反应分布区进行了研究。首次发现黑麦染色体的核仁组成中心区、着丝点和端粒均能用硝酸银染色。对此现象的原因进行了讨论。     

An LC-MS/MS assay to determine plasma pharmacokinetics of cyclic thymic hexapeptide (cTP6) in rhesus monkeys

A robust and simple method for absolute quantification of a novel bidirectional immunomodulatory drug candidate, cyclic thymic hexapeptide (cTP6), in rhesus monkey plasma was developed and validated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Plasma proteins were precipitated by adding four volumes of acetonitrile. Peptides in the supernatant were separated by liquid chromatography on an Agilent Zorbax Eclipse Plus-C18 chromatographic column with gradient elution using 0.1% formic acid in water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) at 0.2 mL/min. The analytes were identified by triple quadrupole mass spectrometry in positive ion-mode. The assay was linear over a concentration range of 10-5000 ng/mL for cTP6, with a lower limit of quantification (LLOQ) of 10 ng/mL. Intra- and inter-day precision of the assay at three concentrations were 1.51-7.70% with accuracy of 95.1-104.2%. The average recovery of cTP6 for three concentration levels was 59.6-64.0%. No significant matrix effect was observed. Peptide cTP6 was detected in plasma of live rhesus monkeys up to 6-8h after intra-muscular injection. The half-life was 2.24-2.95 h. The result revealed a nonlinear pharmacokinetic response to increasing doses of cTP6 (100, 200, 500 μg/kg). For the multiple dose study of cTP6, the drug did not accumulate during daily administration at 100 μg/kg for 7 consecutive days in rhesus monkeys.     

Liquid Norbornadiene Photoswitches for Solar Energy Storage

Due to high global energy demands, there is a great need for development of technologies for exploiting and storing solar energy. Closed cycle systems for storage of solar energy have been suggested, based on absorption of photons in photoresponsive molecules, followed by on‐demand release of thermal energy. These materials are called solar thermal fuels (STFs) or molecular solar thermal (MOST) energy storage systems. To achieve high energy densities, ideal MOST systems are required either in solid or liquid forms. In the case of the latter, neat high performing liquid materials have not been demonstrated to date. Here is presented a set of neat liquid norbornadiene derivatives for MOST applications and their characterization in toluene solutions and neat samples. Their synthesis is in most cases based on solvent‐free Diels‐Alder reactions, which easily and efficiently afford a range of compounds. The shear viscosity of the obtained molecules is close to that of colza oil, and they can absorb up to 10% of the solar spectrum with a measured energy storage density of up to 577 kJ/kg corresponding to 152 kJ mol^–1 (calculated 100 kJ mol^–1). These findings pave the way towards implementation of liquid norbornadienes in closed cycle energy storage technologies.     

LY411575, a potent γ-secretase inhibitor,suppresses osteoclastogenesis in vitro and LPS-induced calvarial osteolysis in vivo

A series of osteolytic bone diseases are usually related to excessive bone resorption and osteoclast formation. Thus, agents or drugs which can target osteoclast development and attenuate bone loss are potentially considerable in preventing and treating of bone lytic diseases. In recent years, many studies have reported that Notch signaling has substantial impacts on the process of osteoclast differentiation, maturation, and bone destruction. In the present study, we showed that LY411575, a γ-secretase inhibitor, could potently suppress osteoclast differentiation, osteoclast-specific gene expression, and bone resorption via suppressing Notch/HES1/MAPK (ERK and p38)/Akt-mediated NFATc1 induction in vitro. Consistent with in vitro results, LY411575 exhibited protective effects in lipopolysaccharides-induced calvarial bone destruction in vivo. Collectively, these results indicate that LY411575 may have therapeutic potential in the treatment of osteoclast-mediated osteolytic bone diseases.