Hyperinsulinemia rather than insulin resistance itself induces blood pressure elevation in high fat diet-fed rats.

OBJECTIVE: To investigate if insulin resistance per se or the accompanying hyperinsulinemia induced hypertension and its underlying mechanisms. METHODS: Sprague-Dawley rats were randomized into normal diet-fed group (ND group) and high-fat diet-fed group (HFD group). Then, the HFD group was further randomly divided into the control group (HFD_C group), the PIO group (treated with pioglitazone), the STZ_DM group (to induce diabetes with streptozotocin) and the DM+Ins group (streptozotocin injection followed by insulin treatment). Insulin sensitivity, plasma insulin, endothelin-1, norepinephrine, aldosterone, angiotensinⅡ and 24-h urinary sodium excretion (USE) levels of the groups were measured and analyzed. A multiple stepwise regression analysis method was applied to exam our hypothesis. RESULTS: Compared to HFD_C group, the groups with lower plasma insulin, the PIO group and STZ_DM group, showed higher USE and lower blood pressure. The groups with higher plasma insulin (but same level of insulin resistance), the HFD_C group and DM+Ins group, showed lower USE and higher blood pressure. The 24-h urinary sodium excretion was the most important contributor to the significant changes of blood pressure with an R2 of 25.2% in this animal experiment. CONCLUSIONS: It is the compensatory hyperinsulinemia rather than insulin resistance per se that causes blood pressure elevation. The urinary sodium excretion is the key mediator among the multiple mechanisms. Therapies targeting hyperinsulinemia and restricting salt intake may favor a better control of hypertension associated with insulin resistance.

Protective effects of butyrate on intestinal ischemia-reperfusion injury in rats.

BACKGROUND: Butyrate is normally fermented from undigested fiber by intestinal microflora. The goal of the present study was to determine the effects of butyrate and its underlying mechanisms on intestinal injury in a rat model of ischemia and reperfusion (I/R). METHODS: Male Sprague-Dawley rats were subjected to warm ischemia for 45 min by clamping the superior mesenteric artery after treatment with butyrate, followed by 6 and 72 h of reperfusion. Pathologic histology analysis, enzyme-linked immunosorbent assay, immunofluorescence, and Western blot were performed. RESULTS: Butyrate preconditioning markedly improved intestinal injury. The inflammatory factor levels and leukocyte infiltration were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, increased the expression of tight junction proteins, and decreased endotoxin translocation. CONCLUSIONS: We conclude that butyrate administration attenuates intestinal I/R injury, which is associated with preservation of intestinal tight junction barrier function and suppression of inflammatory cell infiltration in the intestinal mucosa. This suggests butyrate as a potential strategy to prevent intestinal I/R injury.

Research Progress on Multi-Component Alloying and Heat Treatment of High Strength and Toughness Al-Si-Cu-Mg Cast Aluminum Alloys.

Al-Si-Cu-Mg cast aluminum alloys have important applications in automobile lightweight due to their advantages such as high strength-to-weight ratio, good heat resistance and excellent casting performance. With the increasing demand for strength and toughness of automotive parts, the development of high strength and toughness Al-Si-Cu-Mg cast aluminum alloys is one of the effective measures to promote the application of cast aluminum alloys in the automotive industry. In this paper, the research progress of improving the strength and toughness of Al-Si-Cu-Mg cast aluminum alloys was described from the aspects of multi-component alloying and heat treatment based on the strengthening mechanism of Al-Si-Cu-Mg cast aluminum alloys. Finally, the development prospects of automotive lightweight Al-Si-Cu-Mg cast aluminum alloys is presented.

Research Progress on Microstructure Evolution and Strengthening-Toughening Mechanism of Mg Alloys by Extrusion.

Magnesium and magnesium-based alloys are widely used in the transportation, aerospace and military industries because they are lightweight, have good specific strength, a high specific damping capacity, excellent electromagnetic shielding properties and controllable degradation. However, traditional as-cast magnesium alloys have many defects. Their mechanical and corrosion properties cause difficulties in meeting application requirements. Therefore, extrusion processes are often used to eliminate the structural defects of magnesium alloys, and to improve strength and toughness synergy as well as corrosion resistance. This paper comprehensively summarizes the characteristics of extrusion processes, elaborates on the evolution law of microstructure, discusses DRX nucleation, texture weakening and abnormal texture behavior, discusses the influence of extrusion parameters on alloy properties, and systematically analyzes the properties of extruded magnesium alloys. The strengthening mechanism is comprehensively summarized, the non-basal plane slip, texture weakening and randomization laws are comprehensively summarized, and the future research direction of high-performance extruded magnesium alloys is prospected.

Ultrafine Grain Ferrite Transformed from Fine Austenite Grains Produced by Dynamic Reversal Transformation.

The medium carbon steel warm deformation was carried out in a Gleeble-3500 simulator, and the microstructure was observed on a scan electron microscopy (SEM) and optical microscope (OM). The results show that the dynamic reversal transformation (DRT) of austenite occurred during the multipass deformation at a temperature of 675 °C. The austenite grain size is about 3.4 µm at the stain of 2.67. The thermodynamics was discussed based on the stress activation model. The critical stress of DRT is in the range of 265.94-294.28 MPa, which is related to the Schmit factor, without considering the distortion energy. Meanwhile, the submicron ferrite was obtained after the air cooling stage. The texture of the ultrafine ferrite possessed the characteristics of good, deep drawing properties.

The synthesis of a series of fluorescent emitters and their application for dye lasing and cation sensing.

The following paper reported four carbazole-modified fluorescent emitters. Their molecular structure and electronic transition were analyzed via their single crystal and theoretical calculation. Their photophysical parameters, including absorption, emission and quantum yield, were determined and discussed. It was found that the emission performance of benzo-thiazole-based dyes was better than that of benzo-imidazole-based dyes, owing to the electron-donating effect from the S atom. Upon the presence of metal cations, these photophysical parameters were re-measured. Benzo-thiazole-based dyes were found insensitive towards most metal cations, while benzo-imidazole-based dyes showed obvious photophysical variation upon these metal cations, including absorption red shift and emission quenching. Detailed sensing performance of a representative dye was discussed. A linear working curve with good selectivity was finally observed. Its sensing mechanism was confirmed as the coordination between metal cation and deprotonated benzo-imidazole group. Benzo-thiazole-based dyes showed amplified spontaneous emission (ASE) behavior, with threshold energy of ~220 µJ. Given the optimal condition, a highest ASE efficiency of ~2% was observed, with FWHM value of 6 nm and emission peak of 435 nm. The major novelty and advancement of these fluorescent dyes shall be the stable ASE output (dye 4) under UV excitation and the linear sensing curve with good selectivity (dye 3), which was a hard task for emission turn off sensing probes. We attributed its causation to the valent-recognizing sensing mechanism.

Improved HbA1c and reduced glycaemic variability after 1-year intermittent use of flash glucose monitoring.

Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3-4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p < 0.05), while the TIR increased in the FGM group [(49.39 ± 17.54)% vs (42.44 ± 15.49)%] (p = 0.012). At 48 weeks, the differences were more pronounced (p < 0.01). There were no observed changes in the number of episodes of DKA by the end of the study [(0.25 ± 0.50) vs (0.28 ± 0.51), p = 0.75]. Intermittent use of FGM by T1DM patients can improve their HbA1c and glycaemic control without increasing the hypoglycaemic exposure in insulin-treated individuals with type 1 diabetes in an developing country.

α­lipoic acid can greatly alleviate the toxic effect of AGES on SH­SY5Y cells.

The aim of the study was to explore the influence of α­lipoic acid (α­LA) on the cytotoxicity of advanced glycation end­products (AGEs) against SH­SY5Y cells. AGE­bovine serum albumin (BSA) was incubated in vitro using SH­SY5Y cells as a target model, and the control group was set. Cells were exposed to AGE­BSA, and α­LA was selectively added to the cells. Cell growth and death was determined by the MTT assay, which measures cellular metabolic rate, lactate dehydrogenase (LDH) leakage rate and cellular axonal length. Immunocytochemistry was employed to detect the expression of ß­amyloid (Aß) protein in cells, and mRNA expression of amyloid precursor protein (APP) and the receptor for AGE (RAGE) were assayed by PT­PCR. The metabolism of MTT was clearly increased, the rate of LDH leakage was significantly decreased, and axonal length was significantly increased in cells treated with α­LA (0.1 g/l) as compared to untreated cells. Furthermore, the expression levels of Aß protein were also decreased. In addition, α­LA (0.1 g/l) markedly inhibited the expression of RAGE mRNA, and did not influence APP mRNA expression as compared the control group. α­LA (0.1 g/l) was effective at dampening the cytotoxicity of AGE­BSA, a preliminary observation that confirms the ability of α­LA to significantly alleviate the cytotoxicity of AGEs against SH­SY5Y cells.

Hemoglobin A1c for diagnosis of postpartum abnormal glucose tolerance among women with gestational diabetes mellitus: diagnostic meta-analysis.

OBJECTIVE: To evaluate the accuracy of glycosylated hemoglobin A1c (HbA1c) for the diagnosis of postpartum abnormal glucose tolerance among women with gestational diabetes mellitus (GDM). METHODS: After a systematic review of related studies, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and other measures about the accuracy of HbA1c in the diagnosis of postpartum abnormal glucose tolerance were pooled using random-effects models. The summary receiver operating characteristic (SROC) curve was used to summarize the overall test performance. RESULTS: Six studies met our inclusion criteria. The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.36 (95% CI 0.23-0.52), 0.85 (95% CI 0.73-0.92), 2.4 (95% CI 1.6-3.6), 0.75 (95% CI 0.63-0.88) and 3 (95% CI 2-5). The area under the summary receiver operating characteristic (SROC) curve was 0.67 with a Q value of 0.63. CONCLUSIONS: Measurement of HbA1c alone is not a sensitive test to detect abnormal glucose tolerance in women with prior GDM.

Effects of pioglitazone on high-fat-diet-induced ventricular remodeling and dysfunction in rats.

OBJECTIVE: To investigate the effect of pioglitazone on high-fat (HF)-diet-induced left ventricular (LV) hypertrophy and dysfunction in rats. METHODS: A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups, namely, control, HF diet, and pioglitazone treatment group. High-fat diet group (HF group) animals were treated with HF diet for 30 weeks, whereas pioglitazone group was treated with HF diet for 30 weeks and pioglitazone in the last 6 weeks of the 30-week treatment. Fasting plasma free fatty acids (FFAs), serum, and myocardial triglyceride were measured. Left ventricular function was assessed by echocardiography. Renin, angiotensin II, and angiotensin types 1 and 2 (AT1/AT2) receptors in the myocardium were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). RESULTS: Systolic blood pressure, plasma FFA, serum, and myocardial triglyceride concentrations in HF group were higher than in control and pioglitazone groups (P < .01). There was no significant difference in LV weight index and LV posterior wall thickness between HF and pioglitazone groups; both were higher than in the control group (P < .01). Left ventricular ejection fraction, fraction of shortening, and cardiac index in HF group were lower than in the control and pioglitazone groups (P < .05). Myocardial expression of angiotensin II and AT1 receptor protein in HF group was higher when compared with the control and pioglitazone groups (P < .01). Myocardial renin and angiotensin II messenger RNA (mRNA) in HF group was also higher when compared with the control and pioglitazone groups, whereas the expression of AT2 mRNA was lower (P < .01). CONCLUSION: Pioglitazone diminished HF-diet-induced LV dysfunction. These effects may be related to a reduction in blood pressure, myocardial triglycerides sedimentary, and suppression of renin-angiotensin system.

Elevated serum levels of advanced glycation end products and their monocyte receptors in patients with type 2 diabetes.

BACKGROUND AND AIMS: Animal experiments showed that interaction between advanced glycation end products (AGE) and their receptors (RAGE) play an important role in the pathogenesis of diabetic complications. Soluble RAGE (sRAGE) can function as a decoy for RAGE ligands. The present study aimed to examine the levels of AGEs, RAGE and sRAGE in patients with type 2 diabetes (T2D). METHODS: RAGE gene expression was determined by real-time PCR in 50 patients with T2D (27 men, mean age 52 ± 7.7 years) and 50 age-matched controls without T2D. Serum AGEs and sRAGEs were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum level of AGEs was increased in patients with T2D (10.35 ± 2.27 µg/mL vs.7.69 ± 0.56 µg/mL, p <0.05). sRAGE was decreased in patients with T2D (573.6 ± 172.5 pg/mL vs. 603.4 ± 120.8 pg/mL p <0.01). RAGE gene expression was higher in T2D than in controls (p <0.01). There was an association between monocyte RAGE and serum levels of AGEs in both T2D patients (r = 0.29, p = 0.03) and controls (r = 0.31, p = 0.02). Serum AGEs correlated with homeostasis model assessment of insulin resistance (HOMA-IR) in both patients with T2D (r = 0.322, p = 0.004) and controls (r = 0.281, p = 0.003). CONCLUSIONS: Serum AGEs and monocyte RAGE expression are increased in patients with T2D, whereas serum sRAGE is decreased. Pharmacological intervention on serum AGEs and sRAGE may be a potential therapy for diabetes.