The benefits of oral glucose-lowering agents: GLP-1 receptor agonists, DPP-4 and SGLT-2 inhibitors on myocardial ischaemia/reperfusion injury.

Myocardial infarction (MI) is a life-threatening cardiovascular disease that, on average, results in 8.5 million deaths worldwide each year. Timely revascularization of occluded vessels is a critical method of myocardial salvage. However, reperfusion paradoxically leads to the worsening of myocardial damage known as myocardial ischaemia/reperfusion injury (MI/RI). Therefore, reducing the size of myocardial infarction after reperfusion is critical and remains an important therapeutic goal. The susceptibility of the myocardium to MI/RI may be increased by diabetes. Currently, some traditional antidiabetic agents such as metformin reduce MI/RI by decreasing inflammation, inhibiting oxidative stress, and improving vascular endothelial function. This appears to be a new direction for the treatment of MI/RI. Recent cardiovascular outcome trials have shown that several oral antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sodium-glucose-linked transporter-2 inhibitors (SGLT-2is), not only have good antidiabetic effects but also have a protective effect on myocardial protection. This article aims to discuss the mechanisms and effects of oral antidiabetic agents, including GLP-1RAs, DPP-4is, and SGLT-2is, on MI/RI to facilitate their clinical application.

LncRNA MIR155HG functions as a ceRNA of miR-223-3p to promote cell pyroptosis in human degenerative NP cells.

Nucleus pulposus (NP) cell pyroptosis plays a critical role in the pathogenesis of intervertebral disk degeneration (IDD). MIR155 host gene (MIR155HG) is a long non-coding RNA with pro-inflammatory activity. However, very little is known about its role in NP cell pyroptosis. This study aimed to observe the impact of MIR155HG on cell pyroptosis and to explore the underlying mechanism in human degenerative NP cells. Our results demonstrated that MIR155HG expression was significantly increased in human degenerative NP tissue samples and showed a positive correlation with Pfirrmann score. Overexpression of MIR155HG through a lentiviral vector decreased miR-223-3p levels, up-regulated NLRP3 expression and induced cell pyroptosis in human degenerative NP cells. A ceRNA action mode was identified among MIR155HG, miR-223-3p, and NLRP3. The stimulatory effect of MIR155HG on human degenerative NP cell pyroptosis was significantly reversed by pretreatment with miR-223-3p mimic or NLRP3 siRNA. In summary, these data suggest that MIR155HG sponges miR-223-3p to promote NLRP3 expression, leading to induction of cell pyroptosis in human degenerative NP cells. Targeting MIR155HG could be a novel and promising strategy to slow down the progression of IDD.

Traumatic macular hole study: a multicenter comparative study between immediate vitrectomy and six-month observation for spontaneous closure.

BACKGROUND: Closure of traumatic macular hole (TMH) can be achieved spontaneously or by surgical intervention. Thus far, there exist no prospective comparative studies that have analyzed the difference between the two modalities. This study aimed to compare the anatomical and visual recovery of eyes with TMH following either an immediate vitrectomy or six-month observation. METHODS: This was a multicenter prospective comparative study. Eight centers participated in the study. Patient data from 40 eyes with a recent history of blunt ocular trauma and newly formed full-thickness TMH were recruited in this study. The participating patients selected between an early vitrectomy or a six-month observation after a doctor explained the potential benefits and risks of both strategies in an unbiased manner. Twenty-five patients underwent an immediate vitrectomy, and 15 patients received six-month observation. Patients were assessed by spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). RESULTS: Closure rates were 66.7% for the observational group, and 100% for the surgical group (P=0.002). There were no vision-threatening ocular complications in both groups. For the observational group, the mean closure time was 2.5±1.6 months, and 80% of the hole closure occurred within 3 months; cystic edema on the edge of the hole at baseline was significantly more frequent in the non-closed subgroup than in the closed subgroup (P=0.03). There were no significant differences in the foveal microstructure and in the final visual outcome between the spontaneously closed cases and the surgically closed cases. CONCLUSIONS: TMH had a moderately high incidence of spontaneous closure, but an immediate vitrectomy achieved an even higher closure rate. Vitrectomy was effective and safe to treat TMH, while a 3-month observation for spontaneous closure may be an alternative modality for TMH management. Cystic edema on the edge of the hole may be an unfavorable factor for the spontaneous closure of TMH.

Data analysis in the post-genome-wide association study era.

Since the first report of a genome-wide association study (GWAS) on human age-related macular degeneration, GWAS has successfully been used to discover genetic variants for a variety of complex human diseases and/or traits, and thousands of associated loci have been identified. However, the underlying mechanisms for these loci remain largely unknown. To make these GWAS findings more useful, it is necessary to perform in-depth data mining. The data analysis in the post-GWAS era will include the following aspects: fine-mapping of susceptibility regions to identify susceptibility genes for elucidating the biological mechanism of action; joint analysis of susceptibility genes in different diseases; integration of GWAS, transcriptome, and epigenetic data to analyze expression and methylation quantitative trait loci at the whole-genome level, and find single-nucleotide polymorphisms that influence gene expression and DNA methylation; genome-wide association analysis of disease-related DNA copy number variations. Applying these strategies and methods will serve to strengthen GWAS data to enhance the utility and significance of GWAS in improving understanding of the genetics of complex diseases or traits and translate these findings for clinical applications.

[Higher procalcitonin level in diabetic nephropathy patients compared with healthy volunteers].

OBJECTIVE: To investigate the difference of procalcitonin (PCT) level between uninfected diabetic nephropathy patients and healthy volunteers. METHODS: This study enrolled 76 patients with diabetes only [DM group, 24 h urinary micro albumin (mALB) < 30 mg/24 h], 81 patients with early DN (EDN group, mALB 30-300 mg/24 h), 87 DN patients (DN group, mALB > or = 300 mg/24 h), and 82 age- and sex-matched healthy volunteers. All the patients were free of systemic infection. PCT levels and various laboratory parameters including metabolic and kidney functions as well as inflammatory element profiles were assessed. RESULTS: The PCT level of DN group was significantly higher than that of healthy control group, DM group and EDN group (P < 0.001 or P < 0.05). Spearman's test showed a significant positive correlation between PCT and serum lactate dehydrogenase (LDH, r = 0.541, P < 0.01), Urine acid (UA) (r = 0. 320, P < 0.01), Urea (r = 0.324, P < 0.01), creatinine (Cr) (r= 0.403, P < 0.01), alpha-hydroxybutyrate dehydrogenase (alpha-HBD) (r = 0.791, P < 0.01) and C-reactive protein (CRP) (r = 0.694, P < 0.001) in diabetic nephropathy patients respectively. CONCLUSION: Serum PCT level of patients with diabetic nephropathy is higher than that of healthy volunteers, which may be associated with minimal inflammation and kidney function damage.

Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma.

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan-Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.

EMMNet: sensor networking for electricity meter monitoring.

Smart sensors are emerging as a promising technology for a large number of application domains. This paper presents a collection of requirements and guidelines that serve as a basis for a general smart sensor architecture to monitor electricity meters. It also presents an electricity meter monitoring network, named EMMNet, comprised of data collectors, data concentrators, hand-held devices, a centralized server, and clients. EMMNet provides long-distance communication capabilities, which make it suitable suitable for complex urban environments. In addition, the operational cost of EMMNet is low, compared with other existing remote meter monitoring systems based on GPRS. A new dynamic tree protocol based on the application requirements which can significantly improve the reliability of the network is also proposed. We are currently conducting tests on five networks and investigating network problems for further improvements. Evaluation results indicate that EMMNet enhances the efficiency and accuracy in the reading, recording, and calibration of electricity meters.

[Effects of fluvastatin on the activation of p38 mitogen-activated protein kinase in glomerular mesangial cells under high concentration of glucose].

This study is to investigate the effects of fluvastatin on the activation of p38 mitogen-activated protein kinase (p38 MAPK) and cAMP response element-binding protein (CREB1) in glomerular mesangial cells under high concentration of glucose. High concentration glucose and fluvastatin were used to stimulate the cultured rat glomerular mesangial cells (GMCs) in vitro. The protein expressions of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting. TGF-beta1 and fibronectin (FN) mRNA were measured with reverse transcription and polymerase chain reaction (RT-PCR). The protein synthesis of laminine (LN) and type IV collagen in the supernatants of the GMCs were detected with radioimmunoassay. Compared with low glucose control group, the expressions of p-p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-beta1 mRNA and FN mRNA, LN and type IV collagen in the supernatants were increased significantly in GMCs under high concentration glucose medium. The expression levels of p-p38 MAPK, p-CREB1, TGF-beta1 mRNA, and FN mRNA, LN and type IV collagen in the supernatants were significantly lower in the fluvastatin group than those in the high concentration glucose group. It is concluded that fluvastatin can inhibit over production of TGF-beta1 and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB1.

Two cobalt(II) 5-aminoisophthalate complexes and their stable supramolecular microporous frameworks.

Two stable supramolecular microporous cobalt(II) polymers, namely [Co(HAIP)2]n.3nH2O (1) and [Co(AIP)(H2O)]n (2), AIP = 5-aminoisophthalate, were hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, thermogravimetric analyses, and variable-temperature magnetic susceptibility measurements. The two complexes are constructed from the same Co2(CO2)2 SBU, which is extended into a 1D chain in 1 and a 2D layer in 2. As a result, 1 and 2 are 2D and 3D coordination polymers, respectively. The 3D supramolecular network of complex 1 is held up by strong hydrogen bonds formed between carboxylate groups and shows very high stability when the free H2O molecules are removed, indicating an extraordinarily stable H-bonding system. Upon water ligands being liberated, complex 2 becomes a stable microporous solid with coordination-unsaturated Co centers. The behavior of the susceptibility curve of 1 suggests the occurrence of an interesting intrachain antiferromagnetic coupling between the Co(II) ions and the presence of a significant orbital contribution, whereas the features of 2 indicate an antiferromagnetic coupling with T(N) = 3.5 K and a long-range antiferromagnetic order with a field-induced magnetic transition.