High levels of high-density lipoprotein cholesterol may increase the risk of diabetic kidney disease in patients with type 2 diabetes.

Studies have indicated that low high-density lipoprotein cholesterol (HDL-C) level is an important risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). However, whether higher HDL-C levels decrease the risk of developing DKD remains unclear. This study aimed to clarify the relationship between HDL-C levels and DKD risk in individuals with T2D in China. In total, 936 patients with T2D were divided into DKD and non-DKD groups. The association between HDL-C levels and DKD risk was evaluated using logistic regression analysis and restricted cubic spline curves adjusted for potential confounders. Threshold effect analysis of HDL-C for DKD risk was also performed. Higher HDL-C levels did not consistently decrease the DKD risk. Furthermore, a nonlinear association with threshold interval effects between HDL-C levels and the incidence of DKD was observed. Patients with HDL-C ≤ 0.94 mmol/L or HDL-C > 1.54 mmol/L had significantly higher DKD risk after adjusting for confounding factors. Interestingly, the association between high HDL-C levels and increased DKD risk was more significant in women. A U-shaped association between HDL-C levels and DKD risk was observed; therefore, low and high HDL-C levels may increase the DKD risk in patients with T2D.

[Analysis of SATB2 gene mutation in a child with Glass syndrome].

OBJECTIVE: To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome. METHODS: Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing. RESULTS: The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child. CONCLUSION: The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.

[G protein-coupled receptor 17 is involved in CoCl2-induced hypoxic injury in RGC-5 cells].

OBJECTIVE: To investigate the effect of G protein-coupled receptor 17 (GPR17) on hypoxia injury in retinal ganglion cells in vitro. METHODS: CoCl2 (400 µmol/L) was used to induce hypoxic injury in RGC-5 cells. The expression of GPR17 and the effect of GPR17 ligands were investigated, and the role of GPR17 in hypoxia injury was further studied by transfection of RGC-5 cells with GPR17 small interfering RNA (siRNA). The cell viability was determined by MTT and the cell apoptosis rate was detected by flow cytometry analysis. The expression of GPR17 mRNA was determined with RT-PCR. RESULTS: mRNA expressions of GPR17 in RGC-5 cells with and without CoCl2 treatment were 0.36±0.05 and 0.26±0.08(P<0.01). Compared with hypoxia without any treatment, pretreatment with GPR17 agonists (LTD4, UDP, UDP-G) significantly reduced cell viability (the survival rates of cells decreased by 29.6%, 31.8% and 33.9%, all P<0.01), while the effect of GPR17 antagonist (cangrelor) was the opposite (the survival rates of cells increased by 33.2%, P<0.01). Transfection with GPR17 SiRNA inhibited hypoxia-induced up-expression of GPR17 mRNA (P<0.01)and reduced cell apoptosis[rates of cell apoptosis were(39.73±2.06)%,(42.50±3.64)% and (24.98±2.16)% for blank control, NC siRNA and GPR17 siRNA groups, P<0.01]. CONCLUSIONS: GPR17 may mediate hypoxia injury in RGC-5 cells, while the knockdown of GPR17 can reduce the hypoxia injury.

[Protective effect of grape seed proanthocyanidin on cultured RGC-5 cells against CoCl2-induced hypoxic injury].

OBJECTIVE: To investigate the protective effects of grape seed proanthocyanidin extracts (GSPE) against CoCl2-induced hypoxic injury in cultured RGC-5 cells. METHODS: CoCl2(400 µmol/L) was used to induce hypoxic injury in cultured RGC-5 cells; the cells were pretreated with 0,100,200,400 and 800µmol/L GSPE for 24h. The cell viability was assayed by MTT; the apoptosis was detected by Hoechst 33342 staining; the intracellular reactive oxygen species (ROS) was measured by H2DCFDA oxidative reaction. The mRNA expression of Bcl-2, caspase 9 and caspase 3 was determined by real-time PCR. RESULTS: Compared to hypoxic control group, pretreatment with GSPE significantly increased viability of RGC-5 cells (P<0.001), reduced cell apoptosis (P<0 .001) and intracellular ROS(P <0 .001). In addition, GSPE significantly increased the mRNA expression of Bcl-2(P<0 .001) and decreased mRNA expression of caspase 9(P<0 .001) and caspase 3(P<0 .001) compared to hypoxic control group. CONCLUSION: GSPE may have a protective effect against CoCl2-induced hypoxic injury in cultured RGC-5 cells. The decrease of intercellular ROS, up-regulation of Bcl-2 and down-regulation of caspase 9 and caspase 3 may be involved in the mechanism of the protective effect of GSPE.

Aroma-active components of yeast extract pastes with a basic and characteristic meaty flavour.

BACKGROUND: Aroma-active compounds, together with sugars, amino acids, fat and nucleotides, are the main chemical species determining the characteristic aroma and taste of food. For selecting yeast extract pastes products with a less undesirable aroma, the aroma-active compounds that affect the overall consumer acceptance of yeast extract pastes products were analysed in this work. RESULTS: The aroma-active compounds of yeast extract pastes were extracted by using dynamic headspace extraction or simultaneous distillation extraction, and were detected by gas chromatography-olfactrometry-mass spectrometry in conjunction with dynamic headspace dilution analysis or aroma extract dilution analysis. Sensory results revealed that a meaty, roasted aroma was the dominant of overall aroma. The important aroma-active compounds referred in this work were mainly aldehydes, acids, ketones, furan derivatives, pyrazines, and sulfur-containing compounds. Of these, six volatile compounds such as 3-methylbutanal, 2,3-butanedione, 2,3,5-trimethyl-pyrazin, acetic acid ethenyl ester, 2-acetyl-1-pyrroline and (E,E)-2,4-decadienal had never been reported before as key aroma-active compounds of yeast extract pastes. CONCLUSIONS: The key aroma-active compounds were identified in basic and characteristic meaty flavour yeast extract pastes, and their characterisation was determined.

The proteasome inhibitor bortezomib enhances ATRA-induced differentiation of neuroblastoma cells via the JNK mitogen-activated protein kinase pathway.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Differentiated human NBs are associated with better outcome and lower stage; induction of differentiation is considered to be therapeutically advantageous. All-trans retinoic acid (ATRA) has been shown to induce the differentiation of neuroblastoma (NB) cell lines. The proteasome inhibitor bortezomib inhibits cell growth and angiogenesis in NBs. Here, we investigated the synergistic effect between bortezomib and ATRA in inducing NB cell differentiation in different NB cell lines. Bortezomib combined with ATRA had a significantly enhanced antiproliferative effect. This inhibition was characterized by a synergistic increase in neuronal differentiation. At the same time, the combination therapy showed little neuronal toxicity which was assessed in primary cultures of rat cerebellar granule cells by the MTT assay, PI staining. The combination of bortezomib and ATRA triggered increased differentiation through the activation of proteins, including RARα, RARß, RARγ, p-JNK and p21, compared with ATRA treatment alone. Using JNK inhibitor SP600125 to block JNK-dependent activity, the combination therapy-induced neuronal differentiation was partially attenuated. In addition, p21 shRNA had no effect on the combination therapy-induced neuronal differentiation. The in vivo antitumor activities were examined in human NB cell xenografts and GFP-labeled human NB cell xenografts. Treatment of human NB cell CHP126-bearing nude mice with ATRA plus bortezomib resulted in more significant tumor growth inhibition than mice treated with either drug alone. These findings provide the rationale for the development of a new therapeutic strategy for NB based on the pharmacological combination of ATRA and bortezomib.

Sequencing and genetic variation of multidrug resistance plasmids in Klebsiella pneumoniae.

BACKGROUND: The development of multidrug resistance is a major problem in the treatment of pathogenic microorganisms by distinct antimicrobial agents. Characterizing the genetic variation among plasmids from different bacterial species or strains is a key step towards understanding the mechanism of virulence and their evolution. RESULTS: We applied a deep sequencing approach to 206 clinical strains of Klebsiella pneumoniae collected from 2002 to 2008 to understand the genetic variation of multidrug resistance plasmids, and to reveal the dynamic change of drug resistance over time. First, we sequenced three plasmids (70 Kb, 94 Kb, and 147 Kb) from a clonal strain of K. pneumoniae using Sanger sequencing. Using the Illumina sequencing technology, we obtained more than 17 million of short reads from two pooled plasmid samples. We mapped these short reads to the three reference plasmid sequences, and identified a large number of single nucleotide polymorphisms (SNPs) in these pooled plasmids. Many of these SNPs are present in drug-resistance genes. We also found that a significant fraction of short reads could not be mapped to the reference sequences, indicating a high degree of genetic variation among the collection of K. pneumoniae isolates. Moreover, we identified that plasmid conjugative transfer genes and antibiotic resistance genes are more likely to suffer from positive selection, as indicated by the elevated rates of nonsynonymous substitution. CONCLUSION: These data represent the first large-scale study of genetic variation in multidrug resistance plasmids and provide insight into the mechanisms of plasmid diversification and the genetic basis of antibiotic resistance.

Bortezomib induces apoptosis in human neuroblastoma CHP126 cells.

Neuroblastoma (NB), the most frequent solid tumor of early childhood, is diagnosed as a disseminated disease in >60% of cases, and several lines of evidence support the resistance to apoptosis as a prerequisite for NB progression, and new treatment modalities or potent drugs are further needed. Bortezomib owns a substantial cytotoxicity through regulating degradation of protein associated with cell cycle control and tumor growth. The involvement of bortezomib in neuroblastoma is largely unkown. The aim of this study was to investigate the effects and mechanisms of bortezomib on human neuroblastoma CHP126 cells. Our results indicated that bortezomib inhibits proliferation of neuroblastoma cells in a time- and dose- dependent manner, and the concentration that caused 50% inhibition of CHP126 cells growth was 11.25 nM. Furthermore, bortezomib-induced proliferation inhibition results from massive cell death characterized by apoptosis. Besides, the NFkappaB pathway was not involved in bortezomib treatment in neuroblastoma CHP126 cells, bortezomib-driven apoptotic events were associated with promoting p21 and Bax expression and down-regulating Bcl-2 expression. Ultimately, caspase-3 was activated and the cleavage of PARP was induced. Above all, our data revealed that bortezomib triggered apoptosis by enhancing the caspase 3 activation and/or modulating the Bax/Bcl-2 balance, and also provided preliminary data for further researches of bortezomib on pediatric neuroblastoma.

Sequence analysis of pKF3-70 in Klebsiella pneumoniae: probable origin from R100-like plasmid of Escherichia coli.

BACKGROUND: Klebsiella pneumoniae is a clinically significant species of bacterium which causes a variety of diseases. Clinical treatment of this bacterial infection is greatly hindered by the emergence of multidrug-resistant strains. The resistance is largely due to the acquisition of plasmids carrying drug-resistant as well as pathogenic genes, and its conjugal transfer facilitates the spread of resistant phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: The 70,057 bp plasmid pKF3-70, commonly found in Klebsiella pneumoniae, is composed of five main functional modules, including regions involved in replication, partition, conjugation, transfer leading, and variable regions. This plasmid is more similar to several Escherichia coli plasmids than any previously reported K. pneumoniae plasmids and pKF3-70 like plasmids share a common and conserved backbone sequence. The replication system of the pKF3-70 is 100% identical to that of RepFII plasmid R100 from E. coli. A beta-lactamase gene ctx-m-14 with its surrounding insertion elements (ISEcp1, truncated IS903 and a 20 bp inverted repeat sequence) may compose an active transposon which is directly bordered by two putative target repeats "ATTAC." CONCLUSIONS/SIGNIFICANCE: The K. pneumoniae plasmid pKF3-70 carries an extended-spectrum beta-lactamase gene, ctx-m-14. The conjugative characteristic makes it a widespread plasmid among genetically relevant genera which poses significant threat to public health.

Function of retinoid acid receptor alpha and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis.

All-trans-retinoic acid (ATRA) is a morphogenetic signalling molecule derived from vitamin A and is used clinically to target acute promyelocytic leukemia by inducing differentiation of immature blood cells. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Retinoic acid receptors consist of RARalpha, RARbeta and RARgamma isotypes. Among these components, RARalpha is preferentially bound to ATRA, which is used to treat acute T-lymphoblastic leukemia, yet the conditions and mechanisms remain unknown. In this study, we have demonstrated that, in human acute T-lymphoblastic leukemia Molt3 cells, inhibition of RA-induced proliferation results from massive cell death characterised by apoptosis. The effect of ATRA:RARalpha binding on apoptosis in Molt3 cells has been investigated. Consequently, it has been shown that, in RA-treated Molt3 cells, upregulation of p21 due to RA accompanies caspase 3/PARP activation which precedes the occurrence of apoptosis.

Translation of an effective tai chi intervention into a community-based falls-prevention program.

Tai chi--moving for better balance, a falls-prevention program developed from a randomized controlled trial for community-based use, was evaluated with the re-aim framework in 6 community centers. The program had a 100% adoption rate and 87% reach into the target older adult population. All centers implemented the intervention with good fidelity, and participants showed significant improvements in health-related outcome measures. This evidence-based tai chi program is practical to disseminate and can be effectively implemented and maintained in community settings.

Aerial lift fall injuries: a surveillance and evaluation approach for targeting prevention activities.

PROBLEM: Work on aerial lift platforms exposes workers to fall hazards. The objective of this study was to identify the most common injury scenarios and determine current research gaps for addressing fall incidents associated with aerial lifts. METHODS: Three databases were searched: Census of Fatal Occupational Injuries (CFOI), NIOSH Fatality Assessment and Control Evaluation (FACE) reports, and OSHA Incident Investigation Records. RESULTS: The majority of falls/collapses/tipovers were within the height-category of 10-29 feet. Tipovers comprised 44-46% of boom-lift falls and 56-59% of scissor-lift falls. Constructing and repairing activities were most commonly associated with fall/collapse/tipover incidents. DISCUSSION: CFOI and OSHA/FACE show convergent data, suggesting similar scenarios for aerial lift tipovers. IMPACT ON INDUSTRY: The analysis provides the aerial lift industry information to prioritize their efforts on aerial lift design.

The provisional license: nighttime and passenger restrictions--a literature review.

PROBLEM: Due to inexperience and inadequate driving skills, the road is a very risky place for young and beginning drivers, yet such experience and skills can only be built by increased driving and exposure to risks on the road. Graduated driver licensing (GDL) allows beginning drivers to get their initial driving experience under less risky conditions and gradually eases them into more complex driving situations. This paper reviews the literature exploring two key features of the intermediate licensing phase of GDL, nighttime driving restrictions and passenger restrictions. METHOD: Literature review. RESULTS: Nighttime driving restrictions have been shown to effectively reduce the number and rate of crash involvements on the part of teenage drivers. Data suggest that having passengers in the car increases the likelihood of a fatal injury in young drivers and that this risk increases with the number of passengers. Young drivers were more likely to cause a crash when accompanied by their peers. DISCUSSION: Nighttime driving and passenger restrictions are effective in decreasing injuries among teenage drivers and their passengers, especially in the context of a full GDL system. Several research questions remain to be answered in order to fully refine and optimize the impact of these provisional measures.