22251514
Sonographic evaluation of para- and perirenal fat thickness is an independent predictor of early kidney damage in obese patients
PurposeTo determine whether para- and perirenal fat ultrasonographic thickness (PFUT) is related to increased urinary albumin excretion and whether PFUT is an independent indicator of early kidney damage in obese subjects.MethodSixty-seven nonhypertensive, nondiabetic obese patients and 34 age- and sex-matched normal healthy volunteers were involved in this study. Clinical characteristics, blood biochemistry, PFUT, and urinary albumin/creatinine ratio (ACR) of the subjects were measured. The intraoperator and interoperator coefficient of variation was 5.6 and 3.2 %, respectively.ResultsACR and PFUT were significantly higher in obese patients than those of normal healthy volunteers. PFUT was higher in obese patients with microalbuminuria than those with normoalbuminuria. Correlation analysis showed PFUT had a positive correlation with body mass index (BMI, r = 0.677, P < 0.01), waist circumference (WC, r = 0.686, P < 0.01), plasma free fatty acids (FFAs, r = 0.589, P < 0.01), and ACR (r = 0.610, P < 0.01). ACR had a positive correlation with BMI (r = 0.444, P < 0.01), WC (r = 0.440, P < 0.01), and plasma FFAs (r = 0.496, P < 0.01). Multivariate regression analyses showed that ACR could be predicted by PFUT.ConclusionsPFUT may be an independent predictor of early kidney damage in nonhypertensive, nondiabetic obese patients, and PFUT could be a useful tool for the assessment of visceral fat and early kidney damage in obese patients.
902426
The effect of telomerase activity on vascular smooth muscle cell proliferation in type 2 diabetes in vivo and in vitro.
Serious complications as a result of type 2 diabetes mellitus (T2DM) are becoming a major health concern. In the present study, it was hypothesized that telomerase activity is upregulated in vascular smooth muscle cells (VSMCs) during proliferation in T2DM and that the application of telomerase inhibitors impedes the proliferation of VSMCs in vitro. Male Wistar rats were randomly allocated into the normal control (NC) or diabetic (DM) group. Diabetes was induced by high‑fat feeding and a low dose of streptozotocin (STZ; 30 mg/kg). Primary VSMC cultures were exposed to normal (5.5 mM) or high (25 mM) glucose and insulin (100 nM) in the presence and absence of various concentrations of antisense oligoribonucleotides (ASODNs) for varying lengths of time. Telomerase activity and the proliferation of VSMCs were measured. Results showed that there was a significant increase in the levels of fasting glucose, insulin, triglycerides (TG) and free fatty acids (FFAs) in the diabetic group. Telomerase activity and the proliferation of VSMCs were significantly higher in the diabetic group in vivo and in the high glucose and insulin (HGI)-treated group in vitro (P<0.01). ASODNs significantly inhibited the proliferation of VSMCs in a concentration- and time‑dependent manner (P<0.01). In conclusion, hyperglycemia and hyperinsulinemia stimulate telomerase activity and the proliferation of VSMCs, while the inhibition of telomerase activity reduces the proliferation of VSMCs, indicating that telomerase may be involved in the pathological process of diabetic vascular disease.
9163230
Effect of Aspirin on the Expression of Hepatocyte NF-κB and Serum TNF-α in Streptozotocin-Induced Type 2 Diabetic Rats
Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-β (NF-κB) activation and serum tumor necrosis factor-α (TNF-α). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-α were determined. The expression of NF-κB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-κB expression and serum TNF-α level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-κB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-α (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-κB activation and TNF-α level in streptozotocin-induced type 2 diabetic rats.
37087642
Effect of high free fatty acids on the anti-contractile response of perivascular adipose tissue in rat aorta.
To determine whether high free fatty acids (FFA) could affect the anti-contractile properties of perivascular adipose tissue (PVAT) in rat aortas. Wistar rats were divided into normal, obesity and fenofibrate groups and fed a normal, high-fat, and high-fat plus fenofibrate diet, respectively. Thoracic aortas with or without PVAT (PVAT+ and PVAT-) were prepared with either intact endothelium (E+) or with endothelium removed (E-). Aortas pre-treated with either 500μmol/L of palmitic acid (PA) or physiological salt solution (PSS), as a control, were used for in vitro study. Concentration-dependent responses of aortas to norepinephrine were measured. The anti-contractile effects of PVAT were attenuated in both obese rats with high FFA levels and in the PA group in the presence of endothelium, but not in the absence of endothelium. The attenuation of the anti-contractile effect was restored by reducing FFA levels in the fenofibrate group (P<0.05). Incubation of aortas (PVAT+ E+) with nitric oxide (NO) synthase inhibitor and tumor necrosis factor-alpha (TNF-α) in the normal group caused attenuation of the anti-contractile effect of PVAT (P<0.05). Incubation of aortas (PVAT+ E+) in the obese and PA groups with a NO donor, anti-TNF-α antibodies or free radical scavengers partially restored the anti-contractile effect of PVAT (P<0.05). Under both acute and chronic conditions, high FFA levels could attenuate the anti-contractile properties of PVAT by an endothelium-dependent rather than an endothelium-independent mechanism, in which inflammation and oxidative stress may play important roles.
19235042
Room temperature ionic liquid-mediated molecularly imprinted polymer monolith for the selective recognition of quinolones in pork samples.
A novel molecularly imprinted polymer monolith was prepared by the room temperature ionic liquid-mediated in situ molecular imprinting technique, using norfloxacin (NOR) as the template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker. The optimal synthesis conditions and recognition properties of NOR-imprinted monolithic column were investigated. The results indicated that the imprinted monoliths exhibited good ability of selective recognition against the template and its structural analog. Using the fabricated material as solid-phase extraction sorbent, a sample pre-treatment procedure of molecularly imprinted solid-phase extraction coupling with HPLC was developed for determination of trace quinolone residues in animal tissues samples. The recoveries ranging from 78.16 to 93.50% for eight quinolones antibiotics such as marbofloxacin, NOR, ciprofloxacin, danofloxacin, difloxacin, oxolinic acid, flumequine and enrofloxacin were obtained.
8373412
Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis.
Uncoupling protein 3 (UCP3) is a member of the mitochondrial transporter superfamily that is expressed primarily in skeletal muscle. UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and treatment with glucocorticoids (GCs). The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known. We examined UCP3 gene and protein expression in skeletal muscles from rats after cecal ligation and puncture and from sham-operated control rats. Sepsis resulted in a two- to threefold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased 2.4- to 3.6-fold when incubated muscles from normal rats were treated with dexamethasone (DEX) and/or free fatty acids (FFA) ex vivo. In addition, UCP3 mRNA and protein levels were significantly increased in normal rat muscles in vivo with treatment of either DEX or FFA. The results suggest that sepsis upregulates the gene and protein expression of UCP3 in skeletal muscle, which may at least in part be mediated by GCs and FFA.
241983
Interruption of nuclear localization of ATBF1 during the histopathologic progression of head and neck squamous cell carcinoma.
BACKGROUND
The AT-motif binding factor 1 (ATBF1) gene is frequently altered at the genetic level in several types of cancer, but its protein expression and subcellular localization have not been well studied in human cancers, including head and neck squamous cell carcinomas (HNSCCs).


METHODS
ATBF1 expression and localization were examined in 5 cell lines and 197 clinical specimens of HNSCC, and correlated with pathologic and clinical characteristics.


RESULTS
ATBF1 was predominantly localized in the nucleus of hyperplastic squamous epithelium. Whereas nuclear ATBF1 dramatically decreased in invasive tumors (p = .0012), cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors (p < .0001), and the increase correlated with poor survival. Reduced nuclear ATBF1 level was also detected in HNSCC cell lines.


CONCLUSIONS
Nuclear localization of ATBF1 is frequently interrupted in HNSCC, and the interruption is significantly associated with the progression of HNSCC. The cytoplasmic ATBF1 level could be useful for predicting patient survival.
867040
Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials
BackgroundSubgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.MethodsWe will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.DiscussionA clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.
2135194
A functionally required unfoldome from the plant kingdom: intrinsically disordered N-terminal domains of GRAS proteins are involved in molecular recognition during plant development
The intrinsic disorder is highly abundant in eukaryotic genomes. In the animal kingdom, numerous intrinsically disordered proteins (IDPs) have been characterized, especially in cell signalling and transcription regulation. An intrinsically disordered region often folds in different structures allowing an IDP to recognize and bind different partners at various binding interfaces. In contrast, there have only been a few reports of IDPs from the plant kingdom. Plant-specific GRAS proteins play critical and diverse roles in plant development and signalling and often act as integrators of signals from multiple plant growth regulatory inputs. Using computational and bioinformatics tools, we demonstrate here that the GRAS proteins are intrinsically disordered, thus forming the first functionally required unfoldome in the plant kingdom. Furthermore, the N-terminal domains of GRAS proteins are predicted to contain numerous Molecular Recognition Features (MoRFs), short interaction-prone segments that are located within extended disorder regions and are able to recognize their interacting partners and to undergo disorder-to-order transitions upon binding to these specific partners. Overlapping with the relatively conserved motifs in the N-terminal domains of GRAS proteins, these predicted MoRFs represent the potential protein–protein binding sites and may be involved in molecular recognition during plant development. This study enables us to propose a conceptual framework that guides future experimental approaches to understand structure–function relationships of the entire GRAS family.