Pyruvate dehydrogenase phosphatase1 mRNA expression is divergently and dynamically regulated between rat cerebral cortex, hippocampus and thalamus after traumatic brain injury: A potential biomarker of TBI-induced hyper- and hypo-glycaemia and neuronal vulnerability

Cerebral pyruvate depletion and lactate acidosis are common metabolic characteristics of patients with traumatic brain injury (TBI) and are associated with poor prognosis. Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme coupling glycolysis to mitochondrial tricarboxylic acid (TCA) cycle. Brain PDH activity is regulated by its phosphorylation status and other effectors. Phosphorylation of PDH E1α1 subunit by PDH kinase inhibits PDH activity while dephosphorylation of phosphorylated PDHE1α1 by PDH phosphatase (PDP1) restores PDH activity. In situ hybridization showed that PDP1 mRNA is highly expressed in the cerebral cortex, hippocampus and thalamus of rat. Controlled cortical impact (CCI) induced a significant increase in PDP1 mRNA expression in ipsilateral cerebral cortex at 4h (P<0.05) and 24h post CCI (P<0.01) that returned to basal level 72h post CCI. PDP1 mRNA level increased transiently in ipsilateral hippocampal dentate gyrus and CA1-3 subfields 4h post CCI (P<0.01) but decreased significantly 24h and 72h (P<0.01) post CCI, coinciding with a marked increase in neuronal apoptosis in ipsilateral hippocampus 24h post CCI. PDP1 mRNA expression in thalamus and other subcortical regions decreased persistently post CCI. Contralateral CCI and craniotomy showed similar effects on PDP1 mRNA expression as ipsilateral CCI. Because GFAP mRNA expression was induced in brain regions where PDP1 expression was altered, further study should determine the potential relationship between astrocyte activation, PDP1 alteration, and pyruvate metabolism following TBI.     

The immunomodulation of a novel tumor necrosis factor (CgTNF-1) in oyster Crassostrea gigas

Tumor necrosis factor (TNF) is one of the most important cytokines involved in many processes in both vertebrate and invertebrate. In the present study, a new tumor necrosis factor with a typical TNF domain was identified in oyster Crassostrea gigas (designated CgTNF-1). CgTNF-1 shared low sequence identity and similarity with the TNF superfamily members from other vertebrate and invertebrate. After LPS stimulation, the mRNA expression of CgTNF-1 in haemocytes increased significantly and peaked at 12 h (1.39 ± 0.12, P < 0.05) post treatment, and the expression of CgTNF-1 protein in haemolymph also increased obviously during 6–12 h. When the oyster haemocytes were incubated with rCgTNF-1, its apoptosis and phagocytosis rate were both effectively induced and peaked at 12 h post the treatment of rCgTNF-1 with the concentration of 100 ng mL⁻¹ (23.3 ± 3%, P < 0.01), 50 ng mL⁻¹ (5.3 ± 0.6%, P < 0.05) and 10 ng mL⁻¹ (6.7 ± 1.2%, P < 0.05), respectively. After the co-stimulation of LPS and rCgTNF-1, the apoptosis and phagocytosis rate of oyster haemocytes, and the activities of PO and lysozyme in the haemolymph all increased significantly, and reached the peak at 12 h (apoptosis rate 26.7 ± 1.5%, P < 0.01), 12 h (phagocytosis rate 8.3 ± 0.6%, P < 0.01), 6 h (PO 1.11 ± 0.01 U mg prot⁻¹, P < 0.01) and 12 h (lysozyme 168.9 ± 8.3 U mg prot⁻¹, P < 0.05), respectively, which were significantly higher than that in the LPS group. Furthermore, the anti-bacteria activity in the LPS + TNF group was significantly higher than that in the LPS group during 6–12 h. All the results collectively indicated that CgTNF-1 was involved in the oyster immunity and played a crucial role in the modulation of immune response including apoptosis and phagocytosis of haemocytes, and regulation of anti-bacterial activity as well as the activation of immune relevant enzymes.     

Renal expression of proto-oncogene Ets-1 on matrix remodeling in experimental diabetic nephropathy

The molecular mechanisms of glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN) have received scant attention. Ets-1 proto-oncogene plays a role in matrix remodeling by regulating matrix-degrading enzymes. We investigated the possible role of Ets-1 in the pathogenesis of DN. 6-week-old male Sprague-Dawley rats were divided into two experimental groups as follows: control group (n = 30) and a Diabetes mellitus group (n = 40) induced by injection of streptozotozin (STZ). The rats were investigated at 1, 4, 8, 12 and 16 weeks after STZ-treatment. By means of immunohistochemistry, the expression of Ets-1 in glomeruli was significantly increased in STZ-treated rat kidneys from week 1 (P < 0.05) and reached the peak at week 4 (P < 0.05), followed by a downward trend at subsequent time points. Similarly, the expression of Ets-1 in the tubulointerstitium was also markedly increased from week 1 (P < 0.05) and reached a maximum at week 8 (P < 0.05). By double immunostaining, Ets-1-positive cells were frequently found to co-express matrix metalloproteinase-2 (MMP-2) in STZ-treated rat kidneys. Increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) coincided with increased expression of α-smooth muscle actin (α-SMA) in STZ-induced DN. A positive relationship was observed between the expression of Ets-1 in glomeruli or tubulointerstitium and the expression of MMP-2 (P < 0.01; P < 0.01, respectively) in STZ-treated rat kidneys. The ratio of MMP-2 and TIMP-2 in glomeruli or tubulointerstitium was negatively correlated with deposition of type IV collagen (P < 0.01; P < 0.01, respectively). These findings suggest that Ets-1 may play a critical role in fine-tuning matrix remodeling of STZ-induced DN.     

Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training

Objective

This study investigated how consumption of orange juice associated with aerobic training affected serum lipids and physical characteristics of overweight, middle-aged women.

Methods

The experimental group consisted of 13 women who consumed 500 mL/d of orange juice and did 1 h aerobic training 3 times a week for 3 months. The control group consisted of another 13 women who did the same aerobic training program but did not consume orange juice.

Results

At the end of the experiment, the control group lost an average of 15% of fat mass (P < 0.05) and 2.5% of weight (P < 0.05), whereas the experimental group lost 11% of fat mass and 1.2% of weight (P < 0.05). Consumption of orange juice by the experimental group was associated with increased dietary intake of vitamin C and folate by 126% and 61% respectively. Serum LDL-C decreased 15% (P < 0.05) and HDL-C increased 18% (P < 0.05) in the experimental group, but no significant change was observed in the control group. Both groups improved the anaerobic threshold by 20% (P < 0.05), but blood lactate concentration decreased 27% in the experimental group compared to the 17% control group, suggesting that experimental group has less muscle fatigue and better response to training.

Conclusions

The consumption of 500 mL/d of orange juice associated with aerobic training in overweight women decreased cardiovascular disease risk by reducing LDL-C levels and increasing HDL-C levels. This association also decreased blood lactate concentration and increased anaerobic threshold, showing some improvement in the physical performance.     

Daytime modulation of cortical spreading depression according to blood glucose levels

The aim of this study was to investigate the effects of daytime and blood glucose levels on the propagation of cortical spreading depression (SD). Thirty-nine male Wistar rats were used. Animals were housed 5 per cage with a 12-h, light–dark cycle (lights on at 0600 h). Food and water were available ad libitum, and animals were fasted the night before the experiments. Cortical SD was recorded continuously for 3 h using Ag–AgCl agar-Ringer electrodes placed on the parietal cortex. Every 20 min, SD was elicited by 2% KCl stimulation of the frontal cortex for 1 min. After 1 h of SD-recording, blood glucose levels were measured, and animals were injected intravenously either with glucose (40% solution, 1 mL), insulin (0.3 U/100 g of body weight), or mannitol (20% solution, 1 mL). In the middle of the light period, which corresponds to zeitgeber time (ZT)5, 8 animals received glucose, 7 received insulin, and 6 received mannitol. In another experimental set, glucose or insulin was administered at ZT12 (at the end of the light period); 12 rats received glucose, and 6 received insulin. All the animals that received glucose were hyperglycaemic (P < 0.01), and the hyperglycaemia was less pronounced in the ZT12 group (P < 0.05; Student's t-test). Insulin induced acute hypoglycaemia in animals of both groups (ZT5, P < 0.02; ZT12, P < 0.05; Student's t-test). Glucose injection at ZT5 reduced SD, whereas the insulin ZT5 group showed increased SD propagation (ANOVA, P < 0.05 and 0.01, respectively). Neither glucose nor insulin injection changed SD velocity at ZT12. We concluded that blood glucose levels change the velocity of SD propagation and that these effects are influenced by the daytime. Dark periods seemed to produce a resistance to cortical SD propagation.     

Differential alterations of GABA(A) receptor (α1, β2, γ2 subunit) expression and increased seizure susceptibility in rat offspring from morphine-addicted mothers: beneficial effect of dextromethorphan

Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related posttraumatic stress disorder (PTSD). It has also been known that females are more vulnerable than males in developing anxiety disorders after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB₁ and CB₂) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed rats. Young male and female Sprague-Dawley rats were given 40 unpredictable electric tail-shocks for 2 h daily on 3 consecutive days. CB₁ and CB₂ mRNA and protein levels in rat cerebellum and brain stem were determined using quantitative real-time PCR and Western blot, respectively. Two-way ANOVA revealed significant gender and stress effects on cerebellar CB₁ mRNA expression, with females and non-stressed rats exhibiting higher CB₁ mRNA levels than the males (3 fold, p < 0.01) and stressed rats (30%, p < 0.01), respectively. CB₁ and CB₂ mRNA levels in brain stem were also greater in female rats than males (p < 0.01, p < 0.05, respectively). Repeated stress increased the level of phosphorylated CB₁ receptors, the inactivated CB₁, in rat cerebellum (p < 0.01), particularly in female rats as revealed by the significant gender × stress interaction. Thus, repeated severe stress caused greater CB₁ mRNA suppression and CB₁ receptor phosphorylation in female cerebellum that could lead to increased susceptibility to stress-related anxiety disorders including PTSD.     

Self-management support in “real-world” settings: An empowerment-based intervention

Objective

This study examined the impact of a 6-month, empowerment-based diabetes self-management support (DSMS) intervention on clinical outcomes, self-care behaviors, and quality of life (QOL) compared to a 6-month control period.

Methods

This control-intervention cohort study recruited 77 African-American adults with type 2 diabetes. Baseline, 6-month, and 12-month assessments measured A1C, weight, body mass index (BMI), blood pressure, lipids, self-care behaviors, and QOL. During the control period, participants received weekly educational newsletters. During the intervention period, participants attended weekly DSMS groups as frequently as they needed. Sessions were guided by participants’ self-management questions and concerns, and also emphasized experiential learning, coping, problem-solving, and goal-setting.

Results

The control period found significant improvements for diastolic BP (p < 0.05), serum cholesterol (p < 0.001), following a healthy diet (p < 0.01), and monitoring blood glucose (p < 0.01). The intervention period found significant additional improvements for A1C (p < 0.001), weight (p < 0.05), BMI (p < 0.05), and LDL (p < 0.001). Compared to the control period, participation in the intervention led to a significant reduction in A1C (p < 0.01).

Conclusion

Findings suggest that an empowerment-based, DSMS intervention is promising for improving and/or maintaining diabetes-related health, particularly A1C.

Practical implications

Incorporating empowerment principles in DSMS interventions may be useful for supporting patients’ self-management efforts in “real-world” settings.     

Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury

Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n = 6; CCI-Veh, n = 7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n = 7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p < 0.01) and from CCI-SP scores on days 4, 9 and 14 (p < 0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.     

Antineoplastic effect of calycosin on osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations

Recently, increasing studies have documented that tumorigenesis closely relates to apoptotic processes. Thus, inducing apoptosis is an anti-cancer strategy against osteosarcoma. Here we investigated the anti-proliferative effect of calycosin on human osteosarcoma cell (143B) in vitro. The results showed that calycosin dose-dependently inhibited 143B cell proliferation as reflected in tetrazolium salt (MTT) assay (P < 0.01). In addition, calycosin effectively down-regulated cellular mRNA expressions of IκBα, NF-κB p65 and cyclin D1 through RT-PCR assay (P < 0.01). Next, calycosin-mediated inhibitory effect on 143B tumor-bearing nude mice and the underlying mechanism were evaluated and discussed. As a result, calycosin administration significantly blocked solid tumor growth in 143B-harbored nude mice (P < 0.01). Furthermore, intracellular Bcl-2 protein expression was effectively reduced in 143B-harbored tumor tissue through western blotting analysis (P < 0.01), while intratumoral Apaf-1 and cleaved Caspase-3 protein levels were up-regulated, respectively (P < 0.01). Taken together, calycosin possesses the anti-osteosarcoma potential, in which the mechanism involved was associated with activation of apoptotic, thus inducing apoptosis.     

The relationship between visfatin and metabolic syndrome in postmenopausal women

Objective

The biological role and activity of visfatin, an adipokine mainly produced by visceral fat, has not been fully elucidated. The observed relationships between visfatin and metabolisyndrome are inconsistent. The purpose of this study was to illuminate the relationship between visfatin and metabolic syndrome in postmenopausal women.

Methods

The present study included a sample of 110 postmenopausal Korean women. Subjects with cardiovascular disease or uncontrolled diabetes were excluded from the study sample. Body weight, height, blood pressure (BP), and waist and hip circumference were measured, and biochemical tests were performed.

Results

The mean serum visfatin level (mean ± SD) of subjects with metabolic syndrome was 2.74 ± 1.70 ng/ml. This was significantly higher than the mean level of subjects without metabolic syndrome (p < 0.01). As the number of components of metabolic syndrome increased, the concentration of serum visfatin also increased (p < 0.01). Visfatin concentration was positively correlated with age (r = 0.209, p < 0.05), waist circumference (r = 0.261, p < 0.01), systolic BP (r = 0.255, p < 0.01), diastolic BP (r = 0.252, p < 0.01), fasting glucose level (r = 0.278, p < 0.01), fasting insulin level (r = 0.313, p < 0.01), HOMA-IR (r = 0.345, p < 0.01), total cholesterol level (r = 0.213, p < 0.05), triglyceride level (r = 0.368, p < 0.01), WBC count (r = 0.352, p < 0.01), and homocysteine level (r = 0.196, p < 0.05). Using a multiple logistic regression analysis, visfatin was found to be an independent factor associated with metabolic syndrome after an adjustment for confounding variables including age, body mass index (BMI), and HOMA-IR.

Conclusions

Serum visfatin was associated with metabolic syndrome in postmenopausal women. This suggests that visfatin may act as the underlying pathophysiological trigger for metabolic syndrome in postmenopausal women.     

Changes in body fat percentage during body weight stable conditions of increased daily protein intake vs. control

Objective

The objective of this study was to examine if increased protein intake vs. control influences body fat percentage during stable body weight.

Design

Body composition was assessed before and after a 3-month isoenergetic dietary intervention of 2MJ/d supplements exchanged with 2MJ/d of habitual ad libitum energy intake. The parallel design consisted of protein-rich supplements in the protein group (n = 12) and an isoenergetic combination of carbohydrate and fat supplements in the control group (n = 12). Daily protein intake was calculated from a 24 h urinary nitrogen. Body composition was measured by a combination of underwater-weighing technique, deuterium-dilution technique and whole-body dual-energy X-ray absorptiometry (DXA), a method that allows for estimation of 4-body compartments (fat and lean; water, bone and rest).

Results

Subjects were weight stable and did not change their habitual physical activity. Daily protein intake increased in the protein group during the intervention compared to baseline with + 11 ± 14 g (P < 0.05) vs. the control group that did not change their protein intake − 1 ± 15 g. This resulted in a significant difference in protein intake during the intervention of 80 ± 21 g of the protein group vs. 59 ± 11 g of the control group (P < 0.01). Change in body fat percentage showed a significant group × time interaction of decreased body fat percentage of − 1.0 ± 1.1% of the protein group vs. 0.1 ± 0.6% of the control group (P < 0.05). The group × time interaction of change in fat mass was significant (P < 0.05), and change in fat-free mass was a trend (P = 0.05). Fat-free mass of the protein group had increased with + 0.9 ± 0.6 kg (P < 0.01), and fat mass had decreased with − 0.6 ± 0.8 kg (P < 0.05), while the control group had not changed.

Conclusion

During increased daily protein intake vs. control body fat percentage decreased with unchanged physical activity during 3 months of stable body weight.     

Effect of insulin on the relationship of estrous behaviors to estradiol and LH surges in intact ewes

The objective of this study was to determine whether acute stress alters the frequency of spontaneous estrous behaviors and temporal relationships with preovulatory increases in peripheral plasma estradiol and LH. Follicular phases of intact ewes were synchronized with prostaglandin administered at progesterone pessary withdrawal (PW). Twelve ewes served as controls and 12 were acutely stressed (insulin 4 IU/kg given at 30 and 32 h after PW). Ewes being near to ram(s) 21.3 ± 1.9 h after PW was the first precopulatory behavioral sign and rams nosed the perineal region of ewes after a further 9.0 ± 2.0 h (P < 0.01), with ewes being nudged and mounted by rams 6.8 ± 2.3 h later still (P < 0.01). Insulin did not affect the frequency or timing (relative to PW) of each behavioral sign of estrus. However, within each animal, estradiol values were more than 2 pg/ml lower (P < 0.05) for 6 h following insulin, and the onset of the LH surge was delayed in insulin-treated ewes compared to controls (49.5 ± 3.3 versus 38.2 ± 2.6 h; P = 0.01). Consequently, the interval between the onset of being mounted and the LH surge was longer in insulin-treated ewes compared to controls (10.4 ± 3.0 versus 2.3 ± 0.7 h; P < 0.01). Maximum LH values were also 15 ng/ml lower after insulin (P < 0.01). Thus, acute stress did not alter the timing or frequencies of estrous behaviors but it did reduce estradiol concentrations and delayed the onset and magnitude of the LH surge.     

Protein intake induced an increase in exercise stimulated fat oxidation during stable body weight

Background

Protein-rich weight-loss diets spare fat-free mass at the cost of fat mass. The objective was to examine if there is a change in stimulated fat oxidation related to protein intake during stable body weight.

Methods

Subjects' (BMI 22 ± 2 kg/m², age 25 ± 8 years) maximal fat oxidation (Fat_max) was assessed during a graded bicycle test, before and after a 3-month dietary-intervention of 2 MJ/day supplements exchanged with 2 MJ/d of habitual energy intake. The parallel design consisted of protein-rich supplements in the protein group and an isocaloric combination of carbohydrate and fat supplements in the control group. Daily protein intake was determined according to 24-h urine nitrogen. Body composition was measured according to a 4-compartment model by a combination of underwater-weighing technique, deuterium-dilution technique and whole-body dual-energy X-ray absorptiometry (DXA).

Results

Subjects were weight stable and did not change their physical activity. The protein group (n = 12) increased protein intake (11 ± 14 g, P < 0.05) and had significantly higher daily protein intake vs. control (n = 4) (80 ± 21 vs.59 ± 11 g, P < 0.05). Fat_max increased significantly in the protein group (0.08 ± 0.08 g/min, P < 0.01). Fat-free mass increased independent of change in body weight (P < 0.01), and fat mass and fat percentage decreased (P < 0.05). Change in Fat_max was a function of change in protein intake (r = 0.623, P < 0.05), and not of changes in body composition or VO₂max.

Conclusion

Increased stimulated fat oxidation was related to increased protein intake.     

Mechanism of tyrosine phosphorylation of procaspase-9 and Apaf-1 in cytosolic fractions of the cerebral cortex of newborn piglets during hypoxia

Previous studies have shown that cerebral hypoxia results in increased activity of caspase-9 in the cytosolic fraction of the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypoxia results in increased tyrosine phosphorylation of procaspase-9 and apoptotic protease activating factor-1 (Apaf-1) and the hypoxia-induced increased tyrosine phosphorylation of procaspase-9 and Apaf-1 is mediated by nitric oxide. To test this hypothesis, 15 newborn piglets were divided into three groups: normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic treated with nNOS inhibitor I (Hx + nNOS I 0.4 mg/kg, i.v., 30 min prior to hypoxia) [16]. The hypoxic piglets were exposed to an FiO₂ of 0.06 for 1 h. Tissue hypoxia was documented by ATP and phosphocreatine (PCr) levels. Cytosolic fractions were isolated and tyrosine phosphorylated procaspase-9 and Apaf-1 were determined by immunoblotting using specific anti-procaspase-9, anti-Apaf-1 and anti-phosphotyrosine antibodies. ATP levels (μmoles/g brain) were 4.3 ± 0.2 in the Nx and 1.4 ± 0.3 in the Hx and 1.7 ± 0.3 in Hx + nNOS I group (p < 0.05 vs. Nx) groups. PCr levels (μmoles/g brain) were 3.8 ± 0.3 in the Nx and 0.9 ± 0.2 in the Hx and 1.0 ± 0.4 in the Hx + nNOS I (p < 0.05 vs. Nx) group. Density (OD × mm²) of tyrosine phosphorylatd procaspase-9 was 412 ± 8 in the Nx, 1286 ± 12 in the Hx (p < 0.05 vs. Nx) and 421 ± 10 in the Hx + nNOS I (p < 0.05 vs. Hx) group. Density of tyrosine phosphorylated Apaf-1 was 11.72 ± 1.11 in Nx, 24.50 ± 2.33 in Hx (p < 0.05 vs. Nx) and 16.63 ± 1.57 in Hx + nNOS I (p < 0.05 vs. Hx) group. We conclude that hypoxia results in increased tyrosine phosphorylation of procaspase-9 and Apaf-1 proteins in the cytosolic compartment and the hypoxia-induced increased tyrosine phosphorylation of procaspase-9 and Apaf-1 is mediated by nNOS derived nitric oxide. We propose that increased interaction between the tyrosine phosphorylated procaspase-9 and Apaf-1 molecules lead to increased activation of procaspase-9 to caspase-9 in the hypoxic brain that initiates programmed neuronal death.     

Influence of glucose-lowering rate on CKMB and myoglobin serum levels in type-2 diabetes patients with coronary heart disease

Objective

To analyze the level of creatine kinase isoenzyme (CKMB), myoglobin, to explore the influence of different glucose-lowering rate on cardiac enzyme in type 2 diabetes mellitus patients with coronary heart disease (T2DMC), to search for the rational glucose-lowering rate.

Methods

A total number of 293 type 2 diabetic patients who were hospitalized in the First Affiliated Hospital of Harbin Medical University from May 2008 to December 2009 were recruited. Two groups were divided according to the coronary angiography. 142 subjects of type 2 diabetes mellitus (T2DM) and 151 subjects of T2DMC received intensive glucose therapy. After CKMB and myoglobin being measured, variation and correlation factors were evaluated.

Results

In T2DM group, the level of CKMB was significantly lower at follow-up than that before intensive therapy. Then, we got four subgroups according to the glucose-lowering rate. In T2DM group, when the fasting or postprandial glucose-lowering rate was no more than 6 mmol L⁻¹ d⁻¹, the level of CKMB and myoglobin were significantly lower than that before intensive therapy (P < 0.05). When the fasting glucose-lowering rate is faster than 6 mmol L⁻¹ d⁻¹, the level of CKMB is significantly higher after intensive therapy than that before glucose-lowering (P < 0.05). In T2DMC group, when the fasting or postprandial glucose-lowering rate was not more than 4 mmol L⁻¹ d⁻¹, the level of CKMB and myoglobin was significantly lower than that before intensive therapy (P < 0.05, P < 0.01). When the fasting glucose-lowering rate was faster than 4 mmol L⁻¹ d⁻¹, the level of CKMB and myoglobin was significantly higher at follow-up than that before intensive therapy (P < 0.05). Before intensive therapy, high density lipoprotein cholesterol (HDL-C) has a negative linear regression relationship with CKMB (P < 0.01). Low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) and glycosylated hemoglobin A1c (HbA1c) have a positive linear regression relationship with CKMB (P < 0.05). HDL-C has a negative linear regression relationship with myoglobin (P < 0.01). LDL-C and TG have a positive linear regression relationship with myoglobin (P < 0.01).

Conclusions

T2DM patients, no matter with CHD or not, all have a rational fasting glucose-lowering rate; the fasting glucose-lowering rate is more susceptible to myocardial damage anticipation than the postprandial glucose-lowering rate.     

Expression and significance of leptin receptor,p-STAT3 and p-AKT in diffuse large B-cell lymphoma

We investigated the expression and clinical significance of leptin receptor (OBR), p-STAT3 and p-AKT in patients with diffuse large B-cell lymphoma (DLBCL) by immunohistochemical analysis. Immunohistochemistry revealed high expression of OBR, p-STAT3 and p-AKT in 45.0% (36/80), 28.8% (23/80) and 18.8% (15/80) cases of DLBCL, respectively, and minimal staining in 100% (20/20) cases of RLH (P < 0.05). Compared with GCB group, the non-GCB group had higher p-STAT3 expression rate (21/57 vs. 2/23, P < 0.01). The expression of OBR was positively related with that of p-STAT3 and p-AKT in DLBCL patients (P < 0.05). Our data suggest that OBR stimulates the JAK/STAT and PI3K/AKT signaling pathway and induces the phosphorylation of STAT3 and AKT. This may be involved in carcinogenesis and prognosis of DLBCL. The specific inhibitions could interfere in the combination of leptin with OBR and obstruct the JAK/STAT and PI3K/AKT signaling pathways, which could lead to new research and treatment strategies for DLBCL treatment.     

Combined effect of tumor necrosis factor (TNF)-α and heat shock protein (HSP)-70 in reducing apoptotic injury in hypoxia: A cell culture study

Studies have demonstrated neuroprotective effects of either TNF-α or HSP-70 in ischemia/reperfusion injury following exercise. However, the protective mechanisms involving combined effect of the two proteins, particularly in neuronal apoptosis, remain unclear. This study aims to elucidate the beneficial role of TNF-α and HSP-70 in the regulation of apoptotic proteins and ERK signaling in hypoxic injury. Cortical neurons from 20 Sprague–Dawley rat embryos were isolated and cultured in five groups with or without pretreatment with recombinant TNF-α, HSP-70 protein or both prior to hypoxic conditions: (1) control; (2) control/hypoxia; (3) TNF-α/hypoxia; (4) HSP-70/hypoxia and (5) TNF-α/HSP-70/hypoxia. Western blotting was used to detect pro- and anti-apoptotic proteins, including Bax, AIF, Bcl-xL, Bcl-2, and pERK1/2 protein. TNF-α and HSP-70 significantly (p < 0.05) reduced the levels of pro-apoptotic proteins, Bax and AIF. Also, pretreatment of hypoxic brain tissue with TNF-α and HSP-70 significantly (p < 0.05) enhanced the levels of anti-apoptotic protein, Bcl-xL. TNF-α and HSP-70 together increased Bcl-2 levels by 70%. Hypoxia caused a significant (p < 0.05) increase in ERK1/2 phosphorylation levels by 224%. The most effective inhibition of ERK levels was obtained by the combined administration of TNF-α and HSP-70. This study suggested that TNF-α and HSP-70 together enhance the decrease in pro-apoptotic protein levels and the increase in anti-apoptotic protein levels in the event of neuronal hypoxia through ERK1/2 signal transduction.     

Expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and its correlation with angiogenesis in gastric cancer

Objective

To examine the expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and CD34 in gastric adenocarcinoma, and to investigate their relations with clinical pathology-related factors.

Methods

Immunohistochemistry (IHC) was used to analyze the expression of CEACAM1 and CD34, and micro-vessel density (MVD) marked by CD34 was calculated in 208 cases of human gastric adenocarcinoma and in 56 cases of normal human gastric tissues.

Results

There was no expression of CEACAM1 in normal gastric mucosa. However, all of the gastric adenocarcinoma tissues expressed CEACAM1 with cytoplasmic and/or membranous staining. CEACAM1 expression was classified as high and low (137/208 vs. 71/208, 65.9% vs. 34.1%), the CD34-MVD value was significantly different between the two groups (P < 0.05). In addition, expressions of CEACAM1 and CD34 were significantly different from gastric adenocarcinoma to normal gastric tissues, respectively (P < 0.05). High CEACAM1 expression and high MVD value were positively associated with lymph nodes metastasis and TNM stage, but negatively related to pathological grade (P < 0.05). But they were irrelevant with tumor size, patients’ age and gender (P > 0.05).

Conclusions

The up-regulation of CEACAM1 expression may participate in tumorous angiogenesis, especially high expression of CEACAM1 promoted its capability of invasion and metastasis.     

Relationships between serum uric acid,adiponectin and arterial stiffness in postmenopausal women

Objectives

Cardiovascular disease (CVD) is a leading cause of death in postmenopausal women. Elevated serum uric acid levels, hypoadiponectinemia and arterial stiffness are strongly associated with cardiovascular diseases. We investigated the relationships among uric acid, adiponectin and arterial stiffness in postmenopausal women.

Study design

9555 subjects who had the routine health check-ups, 841 postmenopausal women aged 50 years or older who had not had a menstrual period for more than 12 consecutive months were included in this study.

Main outcome measures

BMI, WC, and serum concentrations of uric acid, adiponectin, glucose, lipids (total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol) were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness.

Results

The subjects were stratified into three groups according to uric acid values. PWV values gradually increased and adiponectin level decreased with uric acid tertiles. Serum uric acid levels in postmenopausal women correlated significantly with age, BMI, WC, TG, HDL-C, insulin, HOMA-IR, adiponectin and PWV. Multiple regression analysis showed that WC (β = 0.141, P < 0.01), HOMA (β = 0.137, P < 0.01), adiponectin (β = −0.104, P < 0.01), and PWV (β = 0.129, P < 0.01) were independently correlated with uric acid levels. In multiple logistic regression analysis after adjusting for risk factors, uric acid was a significant contributor to increased PWV.

Conclusions

These findings indicate that serum uric acid is independently associated with adiponectin and arterial stiffness in postmenopausal women.