Effect of needle-free injection on psychological insulin resistance and insulin dosage in patients with type 2 diabetes.

Background and objective: Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control. Results: After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001). Conclusion: NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2400083658.

L4/5 Disc Herniation: Not Unusually Accompanied with L5/S1 Low-Grade Spondylolytic Spondylolisthesis.

OBJECTIVE: Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low-grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low-grade IS patients. METHODS: A total of 268 consecutive patients diagnosed as L5/S1 low-grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non-disc herniation group (L4/5 non-DH). Radiographic parameters were measured, and the ratios of L4-S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent-samples t-test and χ2 -test) and multiple logistic regression analysis were performed to analyze the data. RESULTS: There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non-DH group. In contrast to the L4/5 non-DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p < 0.001), and lower L5 slip percentage (p = 0.022) were significantly associated with the occurrence of L4/5 DH. CONCLUSIONS: L4/5 disc herniation is not unusually accompanied by L5/S1 low-grade IS. Advanced L4/5 disc degeneration, decreased L4/5 disc height, and lower L5 slip percentage might be significantly associated with L4/5 disc herniation.

Not All Osteophytes Are Located on the Right Side of the Vertebrae in Diffuse Idiopathic Skeletal Hyperostosis: A Quantitative Analysis in Relation to the Position of Aorta.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by osteophytes in the anterior vertebrae, and the presence of aorta may have an impact on their formation. However, the anatomical positional relationship between the aorta and osteophytes in patients with DISH remains controversial. This study aimed to evaluate the position of osteophytes in relation to aorta in DISH, and the influence of aortic pulsation on the formation of osteophytes from the perspective of morphology. METHODS: We conducted a retrospective review of 101 patients diagnosed with DISH and symptomatic lumbar spinal stenosis between June 2018 and December 2021. A total of 637 segments with heterotopic ossification in DISH were used for quantitative measurements on CT scans. The Cartesian coordinate system was built up on the axial CT scans to reflect the relative position between aorta and osteophytes. Osteophytes were divided into adjacent aorta group (AD group) and non-adjacent aorta group (N-AD group). In terms of the morphology, osteophytes in the AD group were further divided into convex, flat, and concave types. The relative position between aorta and osteophytes, and the aorta-osteophyte distance and morphology of osteophytes were compared. Univariate analysis of variance was performed for multiple groups, and two independent-samples t-tests were used for two groups. RESULTS: From T5 to L4, aorta gradually descended from left side to middle of vertebrae, and osteophytes gradually shifted from right side of vertebrae (T5-T10) to bilateral sides (T11-L4). Of 637 osteophytes in DISH, 60.1% (383/637) were in AD group, including convex type 0.6% (4/637), flat type 34.7% (221/637), and concave type 24.8% (158/637). The N-AD group accounted for 39.9% (254/637). Flat osteophytes were concentrated in T5-T12, while concave osteophytes in T11-L4. Overall, the aorta-osteophyte distance of concave type was significantly smaller than that of flat type. CONCLUSION: Osteophytes are not always located on the right side of vertebrae, but move with the position of the descending aorta. Furthermore, the morphology of osteophytes varies by vertebral segment in DISH, which is related to aorta descending anteriorly in the spine.

High Circulating FGF-23 and Its Relationship with Severity of Spinal Involvement in Diffuse Idiopathic Skeletal Hyperostosis.

The primary objective of this study was to determine the role of fibroblast growth factor 23 (FGF-23) in the pathogenesis of diffuse idiopathic skeletal hyperostosis (DISH). A total of 61 patients with DISH and 61 age- and sex-matched control patients without DISH were included in this study. The serum FGF-23, creatinine, inorganic phosphate, calcium, albumin, albumin-adjusted calcium and alkaline phosphatase, and C-reactive protein were assessed in both groups. Based on the extent of ossification, DISH group was further divided into T-DISH and L-DISH subgroups. Data were comparatively analyzed between DISH and Non-DISH groups and among T-DISH, L-DISH, and Non-DISH groups, respectively. Besides, the number of ossification segments of all DISH patients was quantified and the correlation between the number of ossification segments and the serum concentration of FGF-23 was analyzed. The results revealed that serum FGF-23 was significantly higher in DISH group than in Non-DISH group, regardless of gender. Interestingly, serum Pi was significantly lower in DISH group than in Non-DISH group. Moreover, a significant difference in serum FGF-23 among T-DISH, L-DISH, and Non-DISH groups was also observed. In contrast to Non-DISH group, both T-DISH and L-DISH subgroups displayed significantly higher serum FGF-23 level. Although the mean value was relatively higher in L-DISH subgroup, no statistically significant difference was found between T-DISH and L-DISH subgroups. In addition, a moderately positive correlation was identified between the number of ossification segments and the serum level of FGF-23. It can be concluded that serum FGF-23 could serve as a positive biomarker for DISH and may play a significant role in ectopic ossification in DISH.

How does diffuse idiopathic skeletal hyperostosis affect the sagittal spinopelvic alignment in lumbar spinal stenosis patients?

OBJECTIVE: To compare the differences of spinopelvic morphology among patients with DISH, patients without DISH and normal elderly and to assess the impact of ossification extent on sagittal alignment. METHODS: Patients with and without DISH aged > 50 years who required surgery because of lumbar spinal stenosis were enrolled in this cohort(DISH and Non-DISH groups). Also, we collected age-matched normal old outpatients as the control group(Normal group). According to ossification extent, DISH group were divided into two subgroups(T-DISH and L-DISH subgroups). Spinopelvic parameters were measured. Distribution differences of Roussouly classification were analyzed between DISH and Non-DISH group, T-DISH and L-DISH subgroup, respectively. Additionally, distribution difference of kyphotic apex vertebrae between T-DISH and L-DISH subgroup was also investigated. RESULTS: A total of 429 patients (300 males and 129 females) were enrolled in our study, with a mean age of 64.1 ± 5.8 years. Compared to the Normal group, DISH and Non-DISH groups both had significantly higher CSVA, PT, OH, SVA, TPA and lower LL, SS, C7 Tilt, SSA, SPA. Compared to Non-DISH group, DISH group, regardless of ossification extent, had significantly higher T1 slope, CSVA, TK and SVA. Besides, T-DISH subgroup showed significant higher LL, PI, SS and SSA than L-DISH subgroup. There were significant differences of Roussouly classification distribution between T-DISH and L-DISH subgroup. In terms of kyphotic apex location, compared to relatively higher locations in T-DISH subgroup, L-DISH subgroup had apical locations predominantly in the lower thoracic. CONCLUSION: Sagittal spinopelvic alignment is influenced by the presence of DISH and the extent of ossification. Patients with L-DISH have not only increased thoracic kyphosis and forward trunk, but also insufficient lumbar lordosis.

Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis.

Circular RNAs (circRNAs) feature prominently in regulating the progression of tumors, including papillary thyroid carcinoma (PTC). This work is designated to delve into the role of circ_0062389 in PTC. Generally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect circ_0062389, miR-1179 and high mobility group box 1 (HMGB1) mRNA expression levels. RNase R assay was used to verify the circular characteristics of circ_0062389. After circ_0062389 was knocked down in PTC cells, CCK-8 assay was adopted to determine cell viability. Wound healing assay was leveraged to probe cell migration. Besides, Western blot assay was executed to examine the expression levels of HMGB1 and epithelial-mesenchymal transformation (EMT)-related markers (E-cadherin and N-cadherin). Dual-luciferase reporter assay was performed to authenticate the targeting relationships between miR-1179 and circ_0062389, as well as miR-1179 and HMGB1. Here, this work proved that circ_0062389 was greatly up-regulated in PTC tissues and cell lines. The high expression of circ_0062389 was related to large tumor size and positive lymphatic metastasis. Knocking down circ_0062389 could inhibit the proliferation, migration and EMT process of PTC cells. Besides, miR-1179 was a downstream molecule of circ_0062389. Furthermore, miR-1179 inhibitors could partially reverse the above effect of knocking down circ_0062389 on PTC cells. It was also confirmed that HMGB1 was a direct target of miR-1179 and mediated the effects of circ_0062389 and miR-1179 in PTC. Altogether, circ_0062389 can adsorb miR-1179, and regulate HMGB1 expression, thus playing a role in PTC.

Long non-coding RNA PITPNA-AS1 regulates UNC5B expression in papillary thyroid cancer via sponging miR-129-5p.

BACKGROUND: Long non-coding RNA (lncRNA) PITPNA antisense RNA 1 (PITPNA-AS1) expression characteristics, function, and mechanism in papillary thyroid cancer are unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for detecting PITPNA-AS1, UNC-5 netrin receptor B (UNC5B) mRNA, and miR-129-5p expressions in papillary thyroid cancer tissues and cell lines. EdU assay, cell counting kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to investigate the biological functions of PITPNA-AS1 in papillary thyroid cancer. Dual-luciferase reporter assay was utilized for determining whether PITPNA-AS1 and miR-129-5p, as well as UNC5B and miR-129-5p could directly bind to each other. Western blot assay was employed for measuring UNC5B protein expression level in papillary thyroid cancer cell lines. RESULTS: PITPNA-AS1 and UNC5B expressions were markedly increased in papillary thyroid cancer tissues and cell lines while miR-129-5p expression was down-regulated. Knockdown of PITPNA-AS1 could significantly inhibit papillary thyroid cancer cell growth and migration and promote cell apoptosis while UNC5B overexpression plasmids or miR-129-5p inhibitors counteracted the knockdown effect of PITPNA-AS1 on papillary thyroid cancer cells. PITPNA-AS1 targeted miR-129-5p to repress its expression and miR-129-5p targeted UNC5B to repress its expression. Silencing PITPNA-AS1 reduced the expression of UNC5B via regulating miR-129-5p expression. CONCLUSIONS: PITPNA-AS1 facilitated papillary thyroid cancer cell proliferation and migration, and suppressed apoptosis through miR-129-5p/UNC5B axis.

Hotspot Analysis of Traditional Drugs in Diabetes Treatment Literature.

OBJECTIVE: To summarize current hotspots and predict the potential trends in traditional drugs of diabetes treatment for further research. METHODS: Publications on the application of traditional drugs in diabetes treatment were searched from PubMed without language limits. Highly frequent MeSH terms were identified through Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Biclustering analysis results were visualized utilizing the gCLUTO software. Finally, a strategic diagram was generated. RESULTS: Totally 2,386 relevant publications were obtained from PubMed on November 9th, 2018, and 69 highly frequent MeSH terms were identified. Biclustering analysis revealed that these highly frequent MeSH terms were classified into 7 clusters. After calculating the density and centrality of each cluster, strategy diagram was presented. Cluster 0 "Chinese medicine monomers such as antioxidant and hypoglycemic effects" was considered as the most potential research hotspot. CONCLUSIONS: In this study, we found 7 topics related to the application of traditional drugs in diabetes treatment. The molecular mechanisms of Chinese medicine monomers in diabetes could become a potential hotspot with high centricity and low density.

Systematic investigation of the relationships of trimethylamine N-oxide and L-carnitine with obesity in both humans and rodents.

Previous studies suggested the potential associations of trimethylamine N-oxide (TMAO) and its metabolic precursor l-carnitine with obesity. However, existing evidence is limited and inconsistent. In the present study, we perform a cross-sectional analysis of the associations of serum levels of TMAO and l-carnitine with obesity measures, including BMI, body fat distribution and body composition in 1081 participants from the general Newfoundland population. The dietary effects of TMAO and l-carnitine in preventing high fat diet-induced obesity in both male and female mice were also evaluated. We found significant associations between higher serum l-carnitine levels and obesity (higher BMI, body fat mass and VT%) in women, but not in men after controlling multiple confounding factors. Serum TMAO levels were positively associated with age, but not obesity in both men and women. Dietary TMAO had no influence on fat accumulation in high fat diet-fed mice. However, l-carnitine supplementation prevented high fat diet-fed induced obesity in both male and female mice by up-regulating lipolysis and down-regulating lipogenesis in white adipose tissues. The present study provides further evidence for the relationships between TMAO, l-carnitine and obesity.

Portopulmonary hypertension caused by portal hypertension that is complicated by central diabetes insipidus.

We discuss the pathophysiology, diagnosis, differential diagnosis, and therapy of a case with central diabetes insipidus, idiopathic portal hypertension, and portopulmonary hypertension. This report reviews how vasopressin affects those diseases.

Design and validation of a novel hydraulic hybrid vehicle with wheel motors.

With strong demands of energy-saving and environment-friendly vehicles, hydraulic hybrid powertrain is a suitable solution for urban transportation. This article proposes a novel hydraulic hybrid vehicle with wheel motors to improve vehicle power performance and fuel economy. A forward-looking simulation model of the vehicle is built. System parameters are determined according to the power performance demands. A smaller engine is chosen, the peak power of which is reduced by 11.96%. The simulation model is calibrated and verified by experimental tests on the designed test bench. Parameterized simulation results indicate that the acceleration time 0-100 km/h of the designed vehicle is decreased by 36.3% from 19.63 to 12.5 s compared with the conventional vehicle. The maximum vehicle speed is 140 km/h, and the maximum gradeability is 29%. When the engine works in economy mode, fuel consumption is decreased by 35.59% from 15 to 9.66 L per 100 km on the Urban Dynamometer Driving Schedule cycle compared with the conventional vehicle.

Low serum choline and high serum betaine levels are associated with favorable components of metabolic syndrome in Newfoundland population.

BACKGROUND: We investigated the relationships between serum choline and betaine levels with metabolic syndrome-related indices in the general population of Newfoundland. METHODS: 1081 adults were selected from the CODING study. Serum choline and betaine levels were measured. Major confounding factors were controlled in all analyses. RESULTS: Partial correlation and linear regression analysis showed that serum choline levels were positively associated with systolic blood pressure (r: 0.124), serum TG levels (r: 0.132) and negatively correlated with serum glucose levels (r: -0.121) in males (p < 0.01 for all). In females, serum choline levels were positively correlated with serum TG, TC and HDL levels (r: 0.104 to 0.148, p < 0.05 for all). Serum betaine levels were negatively associated with serum TG, TC, LDL and insulin levels, and with atherogenic index and HOMA-IR index in males (r: -0.081 to -0.179, p < 0.05 for all). In females, serum betaine levels were negatively associated with serum TG, hsCRP and insulin levels, and with HOMA-IR index (r: -0.092 to -0.213, p < 0.05 for all). Moreover, subjects with serum choline levels in the highest tertile showed highest serum TG levels and systolic blood pressure in males, and highest serum lipids levels in females. Subjects with the highest serum betaine levels had the lowest serum lipids levels, atherogenic index, IR severity in males, and the lowest serum TG and hsCRP levels, and IR severity in females. CONCLUSION: Low serum choline and high serum betaine levels are associated with favorable components of metabolic syndrome in general adults.

Unfavorable Associations Between Serum Trimethylamine N-Oxide and L-Carnitine Levels With Components of Metabolic Syndrome in the Newfoundland Population.

Background: We aimed to study the relationships between serum Trimethylamine N-oxide (TMAO) and L-carnitine levels with metabolic syndrome profiles, including obesity, blood pressure, serum lipids, serum glucose and insulin resistance (IR)-related index in humans. Methods: Cross-sectional study was performed in 1,081 subjects from the CODING study in Newfoundland. Serum TMAO and L-carnitine levels were quantified by LC-MS/MS. Metabolic markers were measured in all subjects using fasting blood samples. Partial correlation and linear regression analysis were employed after systematically controlling the major confounding factors, such as age, gender, calorie intake and physical activity level. Results: Serum L-carnitine level was positively correlated with serum triglyceride (TG), serum insulin, IR in males with normal fasting glucose (p < 0.05 for all) and positively correlated with only serum TG (p < 0.05) in those with hyperglycemia. In females, significant positive correlations were identified between serum L-carnitine level with obesity, serum total cholesterol, glucose, insulin, and IR in those with normal fasting glucose level (p < 0.05 for all), while none was found in those with hyperglycemia. Serum TMAO level was only identified to be positively correlated with serum insulin level and IR in hyperglycemic males (p < 0.05 for all). Conclusions: Serum L-carnitine level was significantly associated with an unfavorable metabolic syndrome (MS) profile mainly in subjects with normal serum glucose level, while serum TMAO level was associated with an unfavorable MS profile in subjects with hyperglycemia. The gender difference warrants further investigations.

Thyrotropin Regulates eNOS Expression in the Endothelium by PGRN Through Akt Pathway.

To investigate the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in the aorta of subclinical hypothyroidism (SCH) rat model. The mechanisms underlying thyrotropin (TSH) affecting eNOS and PGRN expression in human umbilical vein endothelial cells (HUVECs) cultured in vitro were investigated. In the current study, SCH rat models were established by the administration of L-T4 injection after thyroidectomy in Wistar rats, as opposed to that in the normal and clinical hypothyroidism (CH) groups. The concentrations of NO (pmol/µL) in the SCH and CH groups were significantly lower than that in the normal group (40.8 ± 7.6 and 32.9 ± 10.8 vs. 51.2 ± 12.1, P < 0.05). However, the expression level of eNOS is increased significantly (P < 0.05) in both SCH and CH groups; a similar result was observed for the PGRN protein. In cultured HUVECs, TSH can also up-regulate the expression of eNOS; however, it is accompanied by a reduced concentration of NO and increased level of superoxide anion, thereby indicating uncoupled eNOS. As eNOS is increased, we found that Akt in HUVECs were upregulated by TSH, as well as PGRN expression. While inhibiting the expression of PGRN in HUVECs using siRNA, the expression of eNOS, as well as Akt were also inhibited. In conclusion, SCH can induce vascular endothelial dysfunction in rats, and PGRN participated in the process of TSH-induced expression of Akt/eNOS in the endothelium.

Higher serum choline and betaine levels are associated with better body composition in male but not female population.

BACKGROUND: Animal studies proved that choline and betaine have beneficial effect on reducing body fat. However, evidence in humans is scarce. We aim to investigate the association between serum choline and betaine levels with body composition in general population. METHODS: This is an observational cross-sectional study performed in 1081 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study. Serum choline and betaine levels were measured based on liquid chromatography coupled with tandem mass spectrometry technology. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. RESULTS: Significantly inverse correlations were found between serum betaine levels and all obesity measurements in males (r ranged from -0.12 to -0.23, and p<0.01 for all) but not in females. Serum choline was negatively associated with total percent body fat (%BF), percent trunk fat (%TF), weight, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (r ranged from -0.11 to -0.19, and p<0.05 for all) in males and positively associated with weight, BMI and WC (r ranged from 0.09 to 0.10, and p<0.05 for all) in females. The negative associations between serum choline and betaine levels with obesity in males were more profound in those not on any medication than those taking medications. Moreover, obese males had the lowest serum choline and betaine levels, followed by overweight males, and normal weight males having the highest serum choline and betaine levels, especially in those not taking medications (p<0.05). Likewise, subjects with the highest serum levels of both had the lowest obesity indexes, especially those not taking medications. CONCLUSIONS: Higher serum choline and betaine levels were associated with a more favorable body composition (lower body fat and higher lean body mass) in males and the favorable association was more pronounced in non-medication users.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes.

Obesity-related insulin resistance is associated with chronic systemic low-grade inflammation, and toll-like receptor 4 (TLR4) regulates inflammation. We investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin and TLR4 signaling in adipocytes. Inflammation was induced in adipocytes by lipopolysaccharide (LPS). An antibody against the 67 kDa laminin receptor (67LR, to which EGCG exclusively binds) was used to examine the effect of EGCG on TLR4 signaling, and a TLR4/MD-2 antibody was used to inhibit TLR4 activity and to determine the insulin sensitivity of differentiated 3T3-L1 adipocytes. We found that EGCG dose-dependently inhibited LPS stimulation of adipocyte inflammation by reducing inflammatory mediator and cytokine levels (IKKß, p-NF-κB, TNF-α, and IL-6). Pretreatment with the 67LR antibody prevented EGCG inhibition of inflammatory cytokines, decreased glucose transporter isoform 4 (GLUT4) expression, and inhibited insulin-stimulated glucose uptake. TLR4 inhibition attenuated inflammatory cytokine levels and increased glucose uptake by reversing GLUT4 levels. These data suggest that EGCG suppresses TLR4 signaling in LPS-stimulated adipocytes via 67LR and attenuates insulin-stimulated glucose uptake associated with decreased GLUT4 expression.

Relationship between [corrected] spatial memory in diabetic rats and protein kinase Cγ, caveolin-1 in the hippocampus and neuroprotective effect of catalpol.

BACKGROUND: The mechanisms underlying diabetic encephalopathy are largely unknown, and no effective treatments are available. Catalpol has received much attention due to its numerous biological effects, especially in neuroprotective studies. The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms. METHODS: A rat model of diabetes was established by streptozotocin injection, followed by intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris water maze was used to test the spatial learning performance. Nissl staining was performed to evaluate the morphological changes in the hippocampus. Expression of protein kinase Cγ (PKCγ) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting. Activities of anti-oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits. RESULTS: Significant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated with markedly increased oxidative stress in the brain. Catalpol treatment significantly attenuated cognitive deficits, neuronal damage, and oxidative stress in the brain of diabetic rats. Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats. CONCLUSIONS: Spatial memory in diabetic rats is associated with the expression of PKCγ and Cav-1. Catalpol treatment markedly attenuated oxidative stress, reversed the alteration of PKCγ, Cav-1 and spatial memory deficits.

Effects of selenoprotein S on oxidative injury in human endothelial cells.

BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.

[Relationship of amyloid-ß with vascular endothelial cell damage induced by diabetic serum].

OBJECTIVE: To explore the relationship of the impairment of human umbilical vein endothelial cell (HUVEC) with amyloid-ß. METHODS: HUVECs were cultured in the serum of patients with type 2 diabetes mellitus (DM) or serum of healthy control (HC), while fetal bovine serum (FBS) was used as a negative control. The proliferative activity of HUVEC were assessed by thiazolyl blue tetrazolium bromide (MTT) after 72 h. The supernatant concentrations of superoxide dismutase (SOD), maleic dialdehyde (MDA), nitric oxide (NO), amyloid-ß40 (Aß40) and Aß42 were measured after 0.5, 3 and 72 h respectively. RESULTS: Glycosylated hemoglobin values, fasting plasma glucose and fasting plasma Aß40 concentrations of diabetic patients were higher than those of healthy counterparts (P < 0.01). Proliferative activity of HUVECs in group DM were significantly lower than that of group HC. Both group and the time of intervention had crossover effects on the levels of MDA, SOD, NO and Aß40 ((163 ± 64), (207 ± 69), (286 ± 75) ng/L in group DM; (146 ± 76), (154 ± 75), (161 ± 72) ng/L in group HC after 0.5, 3 and 72 h, P < 0.05) and Aß42 ((48 ± 46), (54 ± 43), (79 ± 44) ng/L in group DM; (41 ± 12), (44 ± 16), (48 ± 12) ng/L in group HC after 0.5, 3 and 72 h, P < 0.05). With the elongating time of intervention, the levels of SOD and NO decreased significantly in group DM and reached the lowest after 72 h while increased significantly in groups HC and FBS and peaked after 72 h. The concentrations of MDA, Aß40 and Aß42 increased significantly in all three groups while the fastest and marked increments were found in group DM (P < 0.01). Pearson correlation analysis showed that SOD was negatively correlated with Aß40 (r = -0.482, P = 0.02) and Aß42 (r = -0.422, P = 0.02) while MDA positively with Aß40 (r = 0.418, P < 0.05) and Aß42 (r = 0.833, P < 0.05) after 72 h. CONCLUSION: Oxidative stress of vascular endothelial cells may be correlated with Aß40 and Aß42 in diabetes.

ELONGATED UPPERMOST INTERNODE encodes a cytochrome P450 monooxygenase that epoxidizes gibberellins in a novel deactivation reaction in rice.

The recessive tall rice (Oryza sativa) mutant elongated uppermost internode (eui) is morphologically normal until its final internode elongates drastically at the heading stage. The stage-specific developmental effect of the eui mutation has been used in the breeding of hybrid rice to improve the performance of heading in male sterile cultivars. We found that the eui mutant accumulated exceptionally large amounts of biologically active gibberellins (GAs) in the uppermost internode. Map-based cloning revealed that the Eui gene encodes a previously uncharacterized cytochrome P450 monooxygenase, CYP714D1. Using heterologous expression in yeast, we found that EUI catalyzed 16alpha,17-epoxidation of non-13-hydroxylated GAs. Consistent with the tall and dwarfed phenotypes of the eui mutant and Eui-overexpressing transgenic plants, respectively, 16alpha,17-epoxidation reduced the biological activity of GA(4) in rice, demonstrating that EUI functions as a GA-deactivating enzyme. Expression of Eui appeared tightly regulated during plant development, in agreement with the stage-specific eui phenotypes. These results indicate the existence of an unrecognized pathway for GA deactivation by EUI during the growth of wild-type internodes. The identification of Eui as a GA catabolism gene provides additional evidence that the GA metabolism pathway is a useful target for increasing the agronomic value of crops.