Caffeamide 36-13 Regulates the Antidiabetic and Hypolipidemic Signs of High-Fat-Fed Mice on Glucose Transporter 4, AMPK Phosphorylation, and Regulated Hepatic Glucose Production

This study was to investigate the antidiabetic and antihyperlipidemic effects of (E)-3-[3, 4-dihydroxyphenyl-1-(piperidin-1-yl)prop-2-en-1-one] (36-13) (TS), one of caffeic acid amide derivatives, on high-fat (HF-) fed mice. The C57BL/6J mice were randomly divided into the control (CON) group and the experimental group, which was firstly fed a HF diet for 8 weeks. Then, the HF group was subdivided into four groups and was given TS orally (including two doses) or rosiglitazone (Rosi) or vehicle for 4 weeks. Blood, skeletal muscle, and tissues were examined by measuring glycaemia and dyslipidemia-associated events. TS effectively prevented HF diet-induced increases in the levels of blood glucose, triglyceride, insulin, leptin, and free fatty acid (FFA) and weights of visceral fa; moreover, adipocytes in the visceral depots showed a reduction in size. TS treatment significantly increased the protein contents of glucose transporter 4 (GLUT4) in skeletal muscle; TS also significantly enhanced Akt phosphorylation in liver, whereas it reduced the expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Moreover, TS enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) both in skeletal muscle and liver tissue. Therefore, it is possible that the activation of AMPK by TS resulted in enhanced glucose uptake in skeletal muscle, contrasting with diminished gluconeogenesis in liver. TS exhibits hypolipidemic effect by decreasing the expressions of fatty acid synthase (FAS). Thus, antidiabetic properties of TS occurred as a result of decreased hepatic glucose production by PEPCK and G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic state by TS in HF-fed mice occurred by regulation of GLUT4, G6Pase, and FAS and phosphorylation of AMPK

Antcin K, a Triterpenoid Compound from Antrodia camphorata

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body of Antrodia camphorata, in vitro and further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptor α (PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia

A systematic approach to detecting transcription factors in response to environmental stresses

Abstract Background Eukaryotic cells have developed mechanisms to respond to external environmental or physiological changes (stresses). In order to increase the activities of stress-protection functions in response to an environmental change, the internal cell mechanisms need to induce certain specific gene expression patterns and pathways by changing the expression levels of specific transcription factors (TFs). The conventional methods to find these specific TFs and their interactivities are slow and laborious. In this study, a novel efficient method is proposed to detect the TFs and their interactivities that regulate yeast genes that respond to any specific environment change. Results For each gene expressed in a specific environmental condition, a dynamic regulatory model is constructed in which the coefficients of the model represent the transcriptional activities and interactivities of the corresponding TFs. The proposed method requires only microarray data and information of all TFs that bind to the gene but it has superior resolution than the current methods. Our method not only can find stress-specific TFs but also can predict their regulatory strengths and interactivities. Moreover, TFs can be ranked, so that we can identify the major TFs to a stress. Similarly, it can rank the interactions between TFs and identify the major cooperative TF pairs. In addition, the cross-talks and interactivities among different stress-induced pathways are specified by the proposed scheme to gain much insight into protective mechanisms of yeast under different environmental stresses. Conclusion In this study, we find significant stress-specific and cell cycle-controlled TFs via constructing a transcriptional dynamic model to regulate the expression profiles of genes under different environmental conditions through microarray data. We have applied this TF activity and interactivity detection method to many stress conditions, including hyper- and hypo- osmotic shock, heat shock, hydrogen peroxide and cell cycle, because the available expression time profiles for these conditions are long enough. Especially, we find significant TFs and cooperative TFs responding to environmental changes. Our method may also be applicable to other stresses if the gene expression profiles have been examined for a sufficiently long time.</p

Experiences with a simple laparoscopic gastric tube construction

BACKGROUND: Minimally invasive esophagectomy (MIE) is a complex operation, and the detailed optimal surgical procedure has not been well described. Our aim was to evaluate use of a simple method of laparoscopic gastric tube construction as minimally invasive surgery for patients with esophageal cancer. METHODS: We performed a retrospective review of 26 consecutive patients who underwent MIE for esophageal cancer in the Koo Foundation Sun Yat-Sen Cancer Center between September 2009 and August 2011. Perioperative data and postoperative complications were statistically analyzed. RESULTS: The patient group consisted of 22 men and 4 women. MIE was performed successfully in all patients. The mean operative time was 430.4 ± 60.6 minutes, and the mean estimated operative blood loss was 135.0 ± 97.8 mL. There were no cases of conversion to open surgery during the procedure. The postoperative complication rate was 53.8%, and there was no surgical mortality. CONCLUSIONS: We recommend this novel method of total laparoscopic staplized formation of gastric tube to facilitate gastric pull-up

Rapid detection of epidermal growth factor receptor mutations with multiplex PCR and primer extension in lung cancer

Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor cells. Almost all of these mutations are located within exons 18-21. The -216 single nucleotide polymorphism in the promoter region is associated with increased EGFR production. We present a method for detecting these common mutations in 81 cases of NSCLC. The protocol is based on the multiplex amplification of promoter region and exons 18-21 of the EGFR genes in a single tube, followed by primer extension of the PCR products using various sizes of primers to detect base changes at -216 promoter region and codons 719, 746-750, 790, 858 of the EGFR gene. We compared the results with that from direct sequencing for detecting EGFR mutations in 81 cases of NSCLC. The two methods identified the same 26 mutations, but our method is superior to direct sequencing in terms of the amount of work and time required. We presented a simple and fast method to detect mutations of EGFR genes in NSCLC

Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA

Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D(3)-trifluoroethanol and in the absence and presence of SDS and D(38)-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations

The role of autologous bone graft in surgical treatment of hypertrophic nonunion of midshaft clavicle fractures

AbstractBackgroundThis study was conducted to evaluate the results of treating hypertrophic nonunion of mid-shaft clavicle fracture with a limited contact dynamic compression plate (LC-DCP) without autologous cancellous bone graft.MethodsFrom 1995 to 2008, 51 cases of hypertrophic nonunion of mid-shaft clavicle fracture were managed with open reduction and internal fixation by LC-DCP without bone graft involvement. Of these 51 cases, 30 had nonunion after failure of initial surgical treatment (Group 1), and 21 had nonunion after failure of conservative treatment (Group 2). Preoperative and postoperative case management were the same for both groups, with the average follow-up period being 20.4 months (range 18–36). Our study evaluated the radiographic results and functional outcomes of these cases according to the quick disability of arm, shoulder, and hand score.ResultsAll 51 cases resulted in uneventful unions. There was no statistically significant difference between the two groups regarding patient demography, cause of injury, preoperative and postoperative functional scores, length of operation, union time, and duration of hospitalization (p>0.05).ConclusionLC-DCP fixation is an effective method for treating hypertrophic nonunion of mid-shaft clavicle fracture. Local bone graft is sufficient to achieve necessary union, and autologous bone graft from other sites of the body appears unnecessary

Operative Treatment of Intra-articular Distal Radius Fractures Using the Small AO External Fixation Device

BackgroundA retrospective group study was done to evaluate the effect of the small AO external fixator in the management of acute intra-articular fractures of the distal radius.MethodsBetween January 1995 and December 1996, 70 consecutive patients with articular fractures of the distal radius were treated by closed reduction and external fixation with small AO external fixators. The mean age at the time of surgery was 58.9 years (range, 14–87 years). There were 58 Colles' Barton's fractures and 12 Smith's Barton's fractures. The follow-up period was 104 months (range, 92–118 months).ResultsAll fractures united in a mean of 5.8 weeks (range, 4–10 weeks). At the final follow-up, the average range of motion was 56.3 ± 11.6° in flexion, 58.6 ± 10.7° in extension, 21.5 ± 4.2° in ulnar deviation, 9.1 ± 2.9° in radial deviation, 71.5 ± 8.5° in pronation, and 67.3 ± 9.2° in supination. Compared with the normal side, the average grip force was 87 ± 6%. The overall clinical and functional outcomes, according to the scoring system of Gartland and Werley, showed that 22 patients (31.4%) had excellent results, 36 (51.4%) had good results, 9 (12.9%) had fair results, and 3 (4.3%) had poor results.ConclusionClosed reduction and external fixation with the small AO external fixator is useful and effective in the management of displaced comminuted articular fractures of the distal radius