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Mitochondria show the special role in cellular bioenergy and many essential physiological activities. Previous researches have suggested that variations of mitochondrial DNA copy number contribute to development of different types of carcinomas. However, the relationship of mtDNA copy number in peripheral blood leukocytes (PBLs) with the risk of head and neck squamous cell carcinoma (HNSCC) is still inconclusive. We investigated the association of mtDNA with HNSCC risk through a case–control study including 570 HNSCC cases and 597 cancer‐free controls. mtDNA copy number in PBLs was measured by real‐time qPCR. Logistic regression was performed to estimate the association between the mtDNA copy number in PBLs and HNSCC risk. A U‐shaped relation between the mtDNA copy number and HNSCC risk was found. Compared with those in the second quartile group, the adjusted odds ratios (ORs) and 95% confidence interval (CI) for those in the first and the forth quartile groups were 1.95 (1.37–2.76) and 2.16 (1.53–3.04), respectively. Using restricted cubic spline analysis, we confirmed such a significant U‐shaped relation. Furthermore, the U‐shaped association remained significant in different subgroups stratified by age, gender, tobacco smoking, and alcohol consumption. Both extremely low and high mtDNA copy numbers had significant associations with the increased HNSCC risk.

Background Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. Methods P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data. Results Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rβ were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rβ expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively. Conclusion High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1145-1154, 2017.

Formate/bicarbonate system has several desirable properties such as noncorrosive and nonirritating nature, as well as facile handling, which make it an attractive candidate for a safe, reversible hydrogen storage material. Herein, Pd nanoparticles supported on mesoporous graphitic carbon nitride (mpg-C3N4) for formate-based reversible hydrogen storage is reported. The as-developed Pd/mpg-C3N4 material was shown to be a superior catalyst for the hydrogenation of high concentrations of bicarbonate to formate under mild conditions. The effects of reaction temperature, H2 pressure, and bicarbonate concentration on the hydrogenation of bicarbonate to formate were investigated. The catalytic performance remained steady with high activity up to six hydrogenation cycles. The interaction between mpg-C3N4 and Pd nanoparticles and the concerted effects of the nitrogen species located at mpg-C3N4 and bicarbonate played a synergetic role in the enhancement of the performance of the catalyst for hydrogenation. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2410–2418, 2016

Objectives Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. Methods Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. Results We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. Conclusion In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.

Insulin resistance is a common metabolic complication of obesity and an important risk factor for the development of type 2 diabetes, the metabolic syndrome, and coronary heart disease (1, 2). It has been proposed that an increase in circulating branched-chain amino acids (BCAA), valine, leucine, and isoleucine, is involved in the pathogenesis of insulin resistance, because increased plasma BCAA concentrations are often observed in obese and insulin resistant states (3, 4), and weight loss leads to decreased plasma BCAA concentrations and improved insulin action (5, 6). However, the underlying mechanism(s) responsible for the relationship between BCAA metabolism and insulin resistance is not known. Monomethyl branched chain fatty acids (mmBCFA) could provide a link between BCAA metabolism and metabolic dysfunction. In most peripheral tissues, BCAA are deaminated by mitochondrial branched chain aminotransferase (BCAT2 or BCATm) to generate branched-chain α-ketoacids (7), which are then decarboxylated by the branched-chain α-ketoacid dehydrogenase complex (8). The resulting short-chain branched acyl moieties can be exported out of mitochondria (9) and undergo conventional de novo fatty acid biosynthesis, catalyzed by fatty acid synthase (FAS), to produce mmBCFA (10). Alternatively, the fatty acyl chain could be extended within mitochondria by using the mitochondrial fatty acid synthesis (FAS II) system (11) (Supplementary Figure S1). The predominant branching in mmBCFA is near the terminal end of the carbon chain with an isopropyl or isobutyl group denoted as iso- or anteiso-BCFA, respectively. mmBCFA are present in a large range of organisms from bacteria to mammals, indicating conserved metabolic pathways for their synthesis and function. The enzymes involved in BCAA metabolism are key regulators of both the degradation of BCAA and the synthesis of mmBCFA. Skeletal muscle and adipose tissue are the primary sites for BCAA degradation (12), whereas BCAA catabolism in the liver is minimal because of low levels of BCATm (7). A study conducted in a rodent model demonstrated that adipose tissue BCAA metabolism can modulate circulating BCAA concentrations (13), presumably because adipose tissue is a major site for plasma BCAA uptake and conversion to lipids (14). Whole tissue assessments of BCAA catabolic activities and kinetics also suggest that adipose tissue could play an important role in regulating whole body BCAA homeostasis in people (15, 16). Adipose tissue gene expression of enzymes involved in BCAA catabolism is lower in obese and insulin resistant mice and people than in their lean counterparts (17, 18). Therefore, it is possible that increased catabolism of BCAA and conversion to mmBCFA in adipose tissue could improve insulin sensitivity by clearing BCAA from plasma. The purpose of the present study was to evaluate the possibility that adipose tissue mmBCFA metabolism is associated with whole-body (primarily skeletal muscle) insulin sensitivity in obese subjects. Accordingly, we conducted: i) a cross-sectional study to assess the relationship between adipose tissue mmBCFA content and insulin sensitivity in lean and obese subjects, and ii) a longitudinal study to assess the effects of marked weight loss on adipose tissue mmBCFA metabolism and insulin sensitivity.

Objective To investigate the efficiency of perforator pedicled propeller flaps for soft tissue coverage of lower leg and foot defects. Methods Twenty patients (12 male, 8 females; mean age 28 years, range, 5–75) with soft tissue defects of the lower leg and foot were retrospectively reviewed. Their defects had been repaired with perforator pedicled propeller flaps from September 2011 to October 2013 and included five cases of injuries caused by spokes, four of infection with postoperative skin necrosis, two of dorsal skin defects caused by heavy objects and nine caused by car accidents. The areas of soft tissue defect were from 2 cm × 8 cm to 10 cm × 20 cm. Fifteen cases had terminal branch of the peroneal artery perforator flaps and five posterior tibia artery perforator flaps, flap size ranging from 5 cm × 11 cm to 12 cm × 28 cm. Color Doppler ultrasound was used to locate all perforator vessels, the calibers of which ranged from 0.8 mm to 1.0 mm. Results The intraoperative coincidence rate of the color Doppler ultrasound was 96.7%. The donor sites were sutured directly in 12 cases and skin grafted in 8. One case had a venous crisis within 24 h that was treated by removal some sutures and drainage. All cases were followed up for 1–18 months; all flaps survived well and pedicles had a satisfactory appearance. The patients were extremely satisfied with the results for repair. Conclusion Perforator pedicled propeller flaps have the advantages over other pedicle flap of being simple, safe, and effective and not involving vascular anastomosis.

Micro-RNAs regulate gene expression by directly binding to the target mRNAs. The goal of the study was to examine the expression profiling of miRNAs in human failing hearts and identify the key miRNAs that regulate molecular signalling networks and thus contribute to this pathological process. The levels of miRNAs and expressed genes were analysed in myocardial biopsy samples from patients with end-stage heart failure (n = 14) and those from normal heart samples (n = 8). Four networks were built including the Gene regulatory network, Signal-Network, miRNA-GO-Network and miRNA-Gene-Network. According to the fold change in the network and probability values in the microarray cohort, RT-PCR was performed to measure the expression of five of the 72 differentially regulated miRNAs. miR-340 achieved statistically significant. miR-340 was identified for the first time in cardiac pathophysiological condition. We overexpressed miR-340 in cultured neonatal rat cardiomyocytes to identify whether miR-340 plays a determining role in the progression of heart failure. ANP, BNP and caspase-3 were significantly elevated in the miR-340 transfected cells compared with controls (P < 0.05). The cross-sectional area of overexpressing miR-340 cardiomyocytes (1952.22 ± 106.59) was greater (P < 0.0001) than controls (1059.99 ± 45.59) documented by Laser Confocal Microscopy. The changes of cellular structure and the volume were statistical significance. Our study provided a comprehensive miRNA expression profiling in the end-stage heart failure and identified miR-340 as a key miRNA contributing to the occurrence and progression of heart failure. Our discoveries provide novel therapeutic targets for patients with heart failure.

J Oral Pathol Med (2012) 41: 621–629 Background: Although autophagy is universally involved in tumorigenesis and tumor progression, the roles of autophagy and autophagy-regulating genes in salivary gland adenoid cystic carcinoma (ACC) remain unknown. In this study, we investigated the expression of the autophagy-regulating genes Beclin-1, death-associated protein kinase-1, ultraviolet radiation resistance–associated gene, and phosphatase and tensin homolog in salivary gland ACC samples. Methods: Immunohistochemistry and real-time polymerase chain reaction were used to analyze the expression of these genes in 89 ACC samples and normal salivary gland tissue samples. The relationship of their expression with clinicopathological features was analyzed. Results: The data showed significantly lower expression of these genes in the tumor samples than in normal salivary gland tissue samples. Furthermore, Beclin-1 expression was significantly correlated with histological pattern of ACC (P

Oral Diseases (2011) 18, 67–73 Objective: Abnormal myelopoiesis especially the expansion of myeloid-derived suppressor cells (MDSCs) is increasingly recognized as an important reason for the escape of tumor from immune surveillance. This study aims to investigate the role of this specific population of cells in oral cancer progression. Materials and Methods: 4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining. The distribution of MDSCs in the spleen and peripheral blood and T cell subsets in the spleen was analyzed by flow cytometry. The expression of MDSCs in the tongue tissues was investigated by immunohistochemical staining, and the expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by real-time PCR. Results: We found that during tumor progression, significantly increased frequency of MDSCs was observed in the spleens and peripheral blood of 4NQO-treated mice, and the frequency of MDSCs in the spleens was positively correlated with systemic CD3+CD8+ T cells. Moreover, 4NQO-treated mice showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor site. Conclusions: Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.