Biological functions and clinic significance of SAF­A (Review).

As one member of the heterogeneous ribonucleoprotein (hnRNP) family, scaffold attachment factor A (SAF-A) or hnRNP U, is an abundant nuclear protein. With RNA and DNA binding activities, SAF-A has multiple functions. The present review focused on the biological structure and different roles of SAF-A and SAF-A-related diseases. It was found that SAF-A maintains the higher-order chromatin organization via RNA and DNA, and regulates transcription at the initiation and elongation stages. In addition to regulating pre-mRNA splicing, mRNA transportation and stabilization, SAF-A participates in double-strand breaks and mitosis repair. Therefore, the aberrant expression and mutation of SAF-A results in tumors and impaired neurodevelopment. Moreover, SAF-A may play a role in the anti-virus system. In conclusion, due to its essential biological functions, SAF-A may be a valuable clinical prediction factor or therapeutic target. Since the role of SAF-A in tumors and viral infections may be controversial, more animal experiments and clinical assays are needed.

Soil enzyme activity mediated organic carbon mineralization due to soil erosion in long gentle sloping farmland in the black soil region.

Soil erosion plays a crucial role in soil organic carbon (SOC) redistribution and mineralization. Meanwhile, the soil extracellular enzymes (EEs) drive C mineralization. However, the response of soil EEs mediated SOC mineralization to soil erosion remains unclear. We investigated the SOC and soil EEs distribution in long gentle sloping farmland (LGSF) under slop-ridge tillage (SRT) and cross-ridge tillage (CRT) in the black soil region (BSR) of northeast China. The results indicated that the SOC mineralization at the upper slope position was higher than that on the toe-slope (133 % âˆ¼ 340 %) under CRT. However, for SRT, SOC mineralization on the back-slope was 126 % and 164 % higher than on the summit- and shoulder-slope. The SOC, dissolved organic carbon (DOC) content, and ß-glucosidase (BG) activities underwent spatial migration and deposition in the lower region under both tillage practices. As for CRT, the SOC content of the back-slope was 19.21 % higher than on the summit-slope, while the DOC content at the back-slope was 29.20 % higher than on the toe-slope. The BG activity was the highest at the toe-slope, followed by the foot-and back-slope, which were 41.74 %-74.73 % higher than at the summit-slope. As for SRT, the SOC, DOC, and BG activities on the back-slope were significantly higher than other slope positions (P < 0.05). The SOC on the back-slope were 47.82 % and 31.72 % higher than those on the summit- and shoulder-slope, respectively. The DOC and BG on the back-slope were 10.98 % and 67.78 % higher than on the summit-slope. The soil EES results indicated strong C and P limitation. Spatial differences in soil C distribution resulted in a significant positive correlation between C limitation and mineralization. This indicated that soil C and nutrient distribution under different slope positions driven by soil erosion, leading to soil nutrient limitation, is a key factor influencing spatial differences in C sources or sinks.

Analgesic Effect and Safety of Lidocaine Liposome vs Oral Sucrose Water in Blood Collection and Intramuscular Injection in Neonates.

Objective: To compare the analgesic effect of oral sucrose water (Su) vs local application of lidocaine liposome (LC) in blood collection and intramuscular injection in neonates. Methods: A total of 300 neonates admitted to Sichuan Provincial People's Hospital in China between June 2019 and December 2021 who were to receive intramuscular injection and heel blood collection were enrolled in the study. The neonates were assigned to one of the following groups (n = 30 in each): control, 30% Su, 25% Su, 24% Su, 12% Su, 8% Su, LC 15-min, LC 30-min, LC 45-min or the combination group. The groups received different concentrations of Su or the application of LC liposome at different timepoints and the control group was given no analgesia. Before and after puncture, the Neonatal Facial Coding System-Revised (NFCS-R) was used for pain evaluation in the neonates. The heart rate (HR), respiratory rate, blood oxygen saturation (SpO2) and blood pressure (BP) in each group were compared, and the starting and ending time of crying and latent crying time were recorded and analyzed. After the optimal concentration of Su and optimal application time of LC were understood, the combination group was used to evaluate the analgesic effect of Su combined with LC. Results: Using various concentrations of Su, neonate pain was alleviated to varying degrees; 24%, 25%, and 30% Su did not reveal any difference in various investigation items, although their effect was superior to 8% and 12% Su. The LC 30-min and LC 45-min groups performed better than the LC 15-min group with regard to NFCS-R score, vital signs and BP. However, no notable difference was observed between the LC 15-min and LC 45-min groups in latent time. Moreover, the combination of 24% Su and application of LC 30 minutes before puncture provided a better analgesic effect than a single anesthesia intervention. Conclusion: The combination of 24% Su and the application of LC 30 minutes before puncture delivered better analgesic effect than a single anesthesia intervention alone.

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus.

Background: Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear. Aim: To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status. Methods: A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models. Results: Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%. Conclusion: This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

Exendin-4 Improves Cognitive Function of Diabetic Mice via Increasing Brain Insulin Synthesis.

BACKGROUND AND OBJECTIVE: Type 2 Diabetes (T2D) patients are more prone to develop Alzheimer's Disease (AD). We have previously shown that Glucagon-like peptide-1 receptor agonist exendin-4 (Ex-4) reduces tau hyperphosphorylation in T2D animals through upregulating insulin signaling, and peripheral injected Ex-4 increases insulin levels in the T2D brain. This study aims to further clarify whether the elevated insulin in the brain is produced by nerve cells under the action of Ex-4. METHODS: The neuronal cell line-HT22 was treated with Ex-4 under high glucose or normal cultivation, and the number of insulin-positive cells as well as the expression levels of insulin synthesis-related genes were examined. The db/db mice were treated with the peripheral injection of Ex-4 and/or IntraCerebroVentricular (ICV) injection of siRNA to inhibit the expression of insulin synthesis- related genes and the behavior tests were carried on. Finally, plasma glucose, Cerebrospinal Fluid (CSF) glucose, CSF insulin, phosphorylation of tau, phosphorylation of AKT and GSK-3ß of db/db mice were detected. RESULTS: We found that Ex-4 promoted the expression of insulin synthesis-related genes and induced an obvious increase of insulin-positive HT-22 neuronal cells in a high glucose environment. Peripheral injection of Ex-4 improved the cognitive function of db/db mice and increased brain insulin levels which activated brain insulin signaling and subsequently alleviated tau hyperphosphorylation. However, when siRNA-neurod1 was injected to block insulin synthesis, the cognitive function of db/db mice was not improved under the action of Ex-4 anymore. Moreover, the brain insulin levels dropped to an extremely low level, and the phosphorylation level of tau increased significantly. CONCLUSION: This study demonstrated that Ex-4 improved cognition function by promoting brain insulin synthesis followed by the activation of brain insulin signaling and alleviation of tau hyperphosphorylation.

Maternal High-Fat Diet Induces Long-Lasting Defects in Bone Structure in Rat Offspring Through Enhanced Osteoclastogenesis.

Maternal stressors during the prenatal and perinatal periods are associated with increased susceptibility for and severity of chronic disease phenotypes in adult offspring. In this study, we used a rat model of maternal high-fat diet (HFD) exposure during pregnancy and lactation to investigate the impact on skeletal homeostasis in offspring. In the distal femur, young male and female offspring (up to 3 weeks of age) from dams fed a HFD exhibited marked increases in trabecular bone volume relative to offspring from dams fed a chow diet, but this was followed by sustained bone loss. By 15 weeks of age, male offspring of HFD fed dams exhibited a 33% reduction in trabecular bone volume fraction that histomorphometric analyses revealed was due to a nearly threefold increase in the abundance of bone-resorbing osteoclasts, while there were no differences between female control and HFD offspring by 15 weeks of age. The osteoblastic differentiation of male offspring-derived bone marrow stromal cells was not affected by maternal diet. However, osteoclastic precursors isolated from the male offspring of HFD fed dams exhibited enhanced differentiation in vitro, forming larger osteoclasts with higher expression of the fusion marker DC-STAMP. This effect appears to be mediated by a cell autonomous increase in the sensitivity of precursors to RANKL. Taken together, these results suggest that maternal stressors like HFD exposure have persistent consequences for the skeletal health of offspring that may ultimately lead to a predisposition for osteopenia/osteoporosis.

Continuous theta burst stimulation dilates meningeal lymphatic vessels by up-regulating VEGF-C in meninges.

BACKGROUND: Lymphatic vessels (LVs) of meninges and lymphatic drainage in the brain have been investigated previously. Here, we examined the role of continuous theta burst stimulation (CTBS) in the modulation of meningeal LVs. METHODS: To explore the effects of CTBS on meningeal LVs, the diameters of LVs were measured between a real CTBS group and sham CTBS group of wild-type male mice. Vascular endothelial growth factor-C (VEGF-C) expression was subsequently calculated in both groups to account for lymphatic changes after CTBS. Sunitinib was administered by 3-day oral gavage to inhibit the VEGF receptor (VEGFR), and the effects of CTBS were further examined in the following groups: vehicle with real CTBS, vehicle with sham CTBS, sunitinib treatment with real CTBS, and sunitinib treatment with sham CTBS. RESULTS: The lymphatic vessels were augmented, and the level of VEGF-C in meninges increased after CTBS. CTBS dilated meningeal lymphatic vessels were impaired after the VEGF-C/VEGFR3 pathway was blocked. CONCLUSIONS: CTBS can dilate meningeal lymphatic vessels by up-regulating VEGF-C in meninges.

Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion.

OBJECTIVE: Deletion of Translin (Tsn) from mice induces an unusual metabolic profile characterized by robust adiposity, normal body weight and glucose tolerance. Translin (TN) protein and its partner, trax (TX), form the TN/TX microRNA-degrading enzyme. Since the microRNA system plays a prominent role in regulating metabolism, we reasoned that the metabolic profile displayed by Tsn KO mice might reflect dysregulation of microRNA signaling. METHODS: To test this hypothesis, we inserted a mutation, E126A, in Tsnax, the gene encoding TX, that abolishes the microRNA-degrading enzymatic activity of the TN/TX complex. In addition, to help define the cell types that drive the adiposity phenotype, we have also generated mice with floxed alleles of Tsn or Tsnax. RESULTS: Introduction of the E126A mutation in Tsnax does not impair expression of TN or TX proteins or their co-precipitation. Furthermore, these mice display selective increases in microRNAs that match those induced by Tsn deletion, confirming that this mutation in Tsnax inactivates the microRNA-degrading activity of the TN/TX complex. Mice homozygous for the Tsnax (E126A) mutation display a metabolic profile that closely mimics that of Tsn KO mice. Selective deletion of Tsn or Tsnax from either adipocytes or hepatocytes, two candidate cell types, does not phenocopy the elevated adiposity displayed by mice with constitutive Tsn deletion or the Tsnax (E126A) mutation. Furthermore, global, conditional deletion of Tsn in adulthood does not elicit increased adiposity. CONCLUSION: Taken together, these findings indicate that inactivation of the TN/TX microRNA-degrading enzyme during development is necessary to drive the robust adiposity displayed by Tsn KO mice.

Rational Interface Engineering for Efficient Flexible Perovskite Light-Emitting Diodes.

Although perovskite light-emitting diodes (PeLEDs) are promising for next-generation displays and lighting, their efficiency is still considerably below that of conventional inorganic and organic counterparts. Significant efforts in various aspects of the electroluminescence process are required to achieve high-performance PeLEDs. Here, we present an improved flexible PeLED structure based on the rational interface engineering for energy-efficient photon generation and enhanced light outcoupling. The interface-stimulated crystallization and defect passivation of the perovskite emitter are synergistically realized by tuning the underlying interlayer, leading to the suppression of trap-mediated nonradiative recombination losses. Besides approaching highly emissive perovskite layers, the outcoupling of trapped light is also enhanced by combining the silver nanowires-based electrode with quasi-random nanopatterns on flexible plastic substrate. Upon the collective optimization of the device structure, a record external quantum efficiency of 24.5% is achieved for flexible PeLEDs based on green-emitting CsPbBr3 perovskite.

TMS brain mapping of the pharyngeal cortical representation in healthy subjects.

BACKGROUND: Brain mapping is fundamental to understanding brain organization and function. However, a major drawback to the traditional Brodmann parcellation technique is the reliance on the use of postmortem specimens. It has therefore historically been difficult to make any comparison regarding functional data from different regions or hemispheres within the same individual. Moreover, this method has been significant limited by subjective boundaries and classification criteria and therefore suffer from reproducibility issues. The development of transcranial magnetic stimulation (TMS) offers an alternative approach to brain mapping, specifically the motor cortical regions by eliciting quantifiable functional reactions. OBJECTIVE: To precisely describe the motor cortical topographic representation of pharyngeal constrictor musculature using TMS and to further map the brain for use as a tool to study brain plasticity. METHODS: 51 healthy subjects (20 male/31 female, 19-26 years old) were tested using single-pulse TMS combined with intraluminal catheter-guided high-resolution manometry and a standardized grid cap. We investigated various parameters of the motor-evoked potential (MEP) that include the motor map area, amplitude, latency, center of gravity (CoG) and asymmetry index. RESULTS: Cortically evoked response latencies were similar for the left and right hemispheres at 6.79 ± 0.22 and 7.24 ± 0.27 ms, respectively. The average scalp positions (relative to the vertex) of the pharyngeal motor cortical representation were 10.40 ± 0.19 (SE) cm medio-lateral and 3.20 ± 0.20 (SE) cm antero-posterior in the left hemisphere and 9.65 ± 0.24 (SE) cm medio-lateral and 3.18 ± 0.23 (SE) cm antero-posterior in the right hemisphere. The mean motor map area of the pharynx in the left and right hemispheres were 9.22 ± 0.85(SE) cm2and 10.12 ± 1.24(SE) cm2, respectively. The amplitudes of the MEPs were 35.94 ± 1.81(SE)uV in the left hemisphere and 34.49 ± 1.95(SE)uV in the right hemisphere. By comparison, subtle but consistent differences in the degree of the bilateral hemispheric representation were also apparent both between and within individuals. CONCLUSION: The swallowing musculature has a bilateral motor cortical representation across individuals, but is largely asymmetric within single subjects. These results suggest that TMS mapping using a guided intra-pharyngeal EMG catheter combined with a standardized gridded cap might be a useful tool to localize brain function/dysfunction by linking brain activation to the corresponding physical reaction.

Continuous theta burst stimulation provides neuroprotection by accelerating local cerebral blood flow and inhibiting inflammation in a mouse model of acute ischemic stroke.

Acute ischemic stroke is a leading cause of disability with limited therapeutic options. Continuous theta burst stimulation (cTBS) has recently been shown to be a promising noninvasive therapeutic strategy for neuroprotection in ischemic stroke patients. Here, we investigated the protective effects of cTBS following acute infarction using a photothrombotic stroke (PTS) model in the right posterior parietal cortex (PPC) of C57BL/6 mice. Treatment with cTBS resulted in a reduction in the volume of the infarct region and significantly increased vascular diameter and blood flow velocity in peri-infarct region, as well as decreased the numbers of calcium binding adapter molecule 1 (Iba-1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes. Moreover, the number of CD16/32 positive microglia was decreased, whereas the number of CD206 positive microglia was increased. In addition, performance in a water maze task was significantly improved. These results indicated that cTBS protected against PPC infarct region, leading to an improvement in spatial cognitive function, possibly as a result of changes to cerebral microvascular function and inflammatory responses.

Nuclear receptor TLX regulates islet beta cell proliferation via E2F6.

Both type 1 and type 2 diabetes are associated with loss of functional beta cell mass, and strategies to restore beta cells are urgently needed. We reported previously that overexpression of the nuclear receptor TLX induces beta cell proliferation, but the underlying molecular mechanism has not been defined. Here, we identified direct targets of TLX in beta cells at the genome-wide level by ChIP-Seq. These targets include a cadre of regulators that are known to be critical for proliferation. Among these ChIP targets, E2F6 was tightly associated with the cell cycle modules, and thus, we further analyzed E2F6 expression and function in beta cells. We showed that E2F6 is strongly downregulated by TLX, and its expression inhibits beta cell proliferation. Moreover, coexpression of E2F6 with TLX partially abrogated the proliferative effects of TLX. These results strongly suggest that TLX acts through E2F6 to regulate beta cell proliferation. Together, the results of this study reveal a direct interaction between TLX and E2F6 and suggest new targets for the expansion of functional beta cell mass.

Long-term liraglutide ameliorates nigrostriatal impairment via regulating AMPK/PGC-1a signaling in diabetic mice.

Growing evidence indicates links between type 2 diabetes and Parkinson's disease. The glucagon-like peptide 1 analogue, liraglutide, a commonly used anti-diabetic drug, has protective effects on neurons. The goal of this study was to determine whether long-term liraglutide treatment could reduce the risk of adult type 2 diabetic mice developing Parkinson's disease. Male diabetic db/db mice (12 weeks old) were injected daily with liraglutide (n = 8), or saline (n = 8), and non-diabetic m/m littermates (n = 6) were included as controls. Motor function was assessed every 4 weeks and all mice were sacrificed after 8 weeks of drug intervention for further analysis. The results revealed that long-term treatment of liraglutide protected the db/db mice against the motor function decay and the dopaminergic neuron loss. Liraglutide also restored the impaired AMP kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1a (PGC-1a) signaling in the striatum of db/db mice. Further experiments in SH-SY5Y cells supported that AMPK is involved in the neuroprotective effect of liraglutide. In summary, long-term liraglutide ameliorated motor dysfunction and dopaminergic neuron impairment in type 2 diabetic mice, probably via enhancing AMPK/PGC-1a signaling.

LncRNA SNHG3 enhances the malignant progress of glioma through silencing KLF2 and p21.

As a newly discovered long non-coding RNA, small nucleolar RNA host gene 3 (SHNG3) has been reported to be dysregulated in certain cancers. Nevertheless, the details about clinical values and biological effects of SNHG3 on glioma are still covered. In this paper, we determined the expression level of SNHG3 in glioma tissues and cells and evaluated the effect of SNHG3 expression on the prognosis of glioma patients. The functional assays were applied to define the effects of SNHG3 on the biological behaviors in glioma including cell proliferation, cell cycle, and apoptosis. It was revealed that SNHG3 was much more enriched in glioma tissues and cell lines than in normal ones. Furthermore, gain- or loss-of-function experiments indicated that the up-regulation of SNHG3 promoted cell proliferation, accelerate cell cycle progress, and repressed cell apoptosis. The mechanistic assays disclosed that SNHG3 facilitated the malignant progression of glioma through epigenetically repressing KLF2 and p21 via recruiting enhancer of zeste homolog 2 to the promoter of KLF2 and p21. Generally, it was exposed that SNHG3 might function as an oncogene in glioma and could be explored as a potential prognostic biomarker and therapeutic target for glioma.

Expression and clinical significance of lncRNAANRILin glioma tissues / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression and clinical significance of lncRNAANRIL in glioma tissues. Methods: 129 cases of glioma tissues and 25 cases of normal brain tissues as control were collected from patients treated in Sichuan Provincial People’ s Hospital from January 01, 2012 to December 30, 2016. Real-time quantitative PCR was used to detect the mRNA expression of lncRNAANRIL; and the relationship between lncRNAANRIL expression and sensitivity of patients to temozolomide as well as the clinical prognosis of glioma patients were analyzed. Results: Compared with control group, the expression of lncRNAANRIL in 129 cases of glioma tissues was significantly increased ([8.730±0.336] vs [1.090±0.137], t=9.957, P<0.01). The expression of lncRNAANRIL in WHO Ⅰ-Ⅱ grade patients was significantly lower than that of patients at grade Ⅲ-Ⅳ ([4.198±0.260] vs [10.550±0.291], t=13.03, P< 0.01). lncRNA ANRIL expression was significantly correlated with WHO stage，the sensitivity to temozolomide（TMZ）and survival status（all P<0.05）, but not associated with gender, age, KPS score and tumor size (all P>0.05). Moreover, Kaplan-Meier analysis demonstrated that decreased lncRNAANRIL expression contributed to significantly longer overall survival ([29.17±0.64] vs [13.54±0.74] months, P<0.01) and recurrence-free survival time ([9.08±0.56] vs [15.88±0.83] months, P<0.01). Univariate and multivariate analysis also indicated that lncRNAANRIL expression, WHO stage and chemosensitivity could be independent prognostic markers for glioma (P<0.05). Conclusion: Higher pathological grade of glioma patients indicates higher lncRNA ANRIL expression and shorter survival time. lncRNAANRIL is involved in the occurrence and development of glioma, and can be used as a molecular marker for the diagnosis and prognosis of glioma.

Triglyceride glucose-body mass index is effective in identifying nonalcoholic fatty liver disease in nonobese subjects.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is highly correlated with obesity; however, it is not uncommon among nonobese individuals. Triglyceride (TG) and glucose index combined with body mass index (TyG-BMI) has been proposed as a favorable marker of insulin resistance. We sought to investigate the effectiveness of TyG-BMI in identifying NAFLD in nonobese subjects.We conducted a cross-sectional study in a nonobese (BMI <25.0 kg/m) Chinese population (N = 6809) of adults who underwent health examinations, including abdominal ultrasonography.The prevalence of ultrasonography-detected NAFLD was 23.9% in nonobese subjects. After adjusting for potential confounders, every 1-standard deviation increase in TyG-BMI had an odds ratio (OR) of 3.4 [95% confidence interval (95% CI), 3.0-3.9] for NAFLD. Compared with the lowest quartile of TyG-BMI, multivariable-adjusted ORs were 2.4 (1.6-3.6), 6.4 (4.2-9.7), and 15.3 (9.8-23.9) for those in the second, third, and fourth quartile, respectively. According to the receiver operating characteristic curve analysis, TyG-BMI was effective in diagnosing patients with NAFLD with an area under the curve of 0.835 (95% CI, 0.824-0.845). In comparison, TyG-BMI was superior to its components, including TyG, BMI, TG, and fasting plasma glucose, for identifying nonobese subjects at risk for NAFLD.In this study, the prevalence of NAFLD was over one-fifth in the nonobese population. TyG-BMI was an effective marker to detect NAFLD in nonobese subjects.

Incretin-based agents in type 2 diabetic patients at cardiovascular risk: compare the effect of GLP-1 agonists and DPP-4 inhibitors on cardiovascular and pancreatic outcomes.

BACKGROUND: Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk. METHODS: Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia. RESULTS: When we evaluated the combined effect of six trials, the results suggested that incretin-based treatment had no significant effect on overall risks of CV and pancreatic outcomes compared with placebo. However, GLP-1As reduced all-cause death (RR = 0.90, 95% CI 0.82-0.98) and CV mortality (RR = 0.84, 95% CI 0.73-0.97), whereas DPP-4Is had no significant effect on CV outcomes but elevated the risk for acute pancreatitis (OR = 1.76, 95% CI 1.14-2.72) and hypoglycemia (both any and severe hypoglycemia), while GLP-1As lowered the risk of severe hypoglycemia. CONCLUSIONS: GLP-1As decreased risks of all-cause and CV mortality and severe hypoglycemia, whereas DPP-4Is had no effect on CV outcomes but increased risks in acute pancreatitis and hypoglycemia.

Combined effect of obesity and uric acid on nonalcoholic fatty liver disease and hypertriglyceridemia.

Hyperuricemia is associated with metabolic syndrome (MetS), but the association is often confounded by the shared background of obesity. We sought to explore the modifying effects of obesity on the association between uric acid (UA), MetS components, and nonalcoholic fatty liver disease (NAFLD).We conducted a cross-sectional study in a Chinese population of 10,069 participants aged ≥20 years. Multiplicative interaction between obesity (BMI ≥25 kg/m) and elevated UA was assessed using an interaction term in a logistic regression analysis. The presence of additive interaction was assessed based on the relative excess risk due to the interaction (RERI) and the attributable proportion due to the interaction (AP).There was no evidence of a multiplicative interaction between obesity and elevated UA on MetS components and NAFLD. However, there was a strong additive interaction between obesity and elevated UA with regard to NAFLD (RERI of 6.47 [95% CI 3.42-9.53] for men and 5.87 [1.55-10.19] for women) and hypertriglyceridemia (RERI of 1.38 [0.57-2.20] for men and 1.38 [0.08-2.67] for women). In addition, 42% and 36% of the increased odds of NAFLD for men and women, respectively, can be explained by an interaction between obesity and elevated UA (AP of 0.42 [95% CI (0.30-0.54)] for men and 0.36 [0.17-0.55] for women). Similarly, the interaction accounted for 27% and 26% of the increased risk of hypertriglyceridemia for men and women (AP of 0.27 [0.14-0.41] for men and 0.26 [0.06-0.47] for women).In this population, obesity and elevated UA synergistically interacted to increase the risk of NAFLD and hypertriglyceridemia.

[Role and mechanism of Salvia miltiorrhiza Bunge in alleviating injury induced by hypoxia/reoxygenation in HK-2 cells].

OBJECTIVE: Salvia miltorrhiza Bunge (SMB) is a traditional Chinese herb, which is considered to promote blood flow and remove blood stasis. This study examined whether SMB can alleviate injury induced by hypoxia/reoxygenation (H/R) in human kidney proximal tubular cells-2 (HK-2 cells). METHODS: There were 3 experimental groups: control, H/R injury and SMB-treated H/R injury. H/R injury of HK-2 cells was induced by first covering the cells with and then removing liquid paraffin wax. Different concentrations of compound SMB solution (0.05%, 0.10%, 0.15% or 0.20%) were administered to the SMB-treated H/R injury group before the hypoxic injury. After 4, 12 and 24 hrs of hypoxia and 4, 12, 24 and 48 hrs of reoxygenation, morphologic changes of HK-2 cells were observed under an inverted microscope. Cell viability was measured by the MTT method. Lactate dehydrogenase (LDH) activity in the culture supernatants was assayed using biochemical methods; TNF-alpha levels were determined by radioimmunoassay (RIA). RESULTS: The number of HK-2 cells was significantly reduced in the H/R injury group after hypoxia, and reached a nadir 24 hrs after hypoxia treatment. Various concentrations of SMB-treated groups showed significantly greater number of HK-2 cells than the H/R injury group. SMB solution (0.10%) produced the best effect. The levels of LDH and TNF-alpha in the H/R injury group were significantly increased, and reached a peak between 24 hrs of hypoxia and 4 hrs of reoxygenation when compared to the control group. Pre-treating with 0.10% SMB resulted in significantly lower levels of LDH and TNF-alpha than in the untreated H/R injury group at various time points of H/R. CONCLUSIONS: SMB has protective effects against H/R injury of HK-2 cells, possibly through inhibition of inflammatory cytokines.