[The role of adenine nucleotide and its metabolites in regulating the homeostasis of glucose and lipid metabolism].

Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.

Ultra-fast pulse propagation in nonlinear graphene/silicon ridge waveguide.

We report the femtosecond laser propagation in a hybrid graphene/silicon ridge waveguide with demonstration of the ultra-large Kerr coefficient of graphene. We also fabricated a slot-like graphene/silicon ridge waveguide which can enhance its effective Kerr coefficient 1.5 times compared with the graphene/silicon ridge waveguide. Both transverse-electric-like (TE-like) mode and transverse-magnetic-like (TM-like) mode are experimentally measured and numerically analyzed. The results show nonlinearity dependence on mode polarization not in graphene/silicon ridge waveguide but in slot-like graphene/silicon ridge waveguide. Great spectral broadening was observed due to self-phase modulation (SPM) after propagation in the hybrid waveguide with length of 2 mm. Power dependence property of the slot-like hybrid waveguide is also measured and numerically analyzed. The results also confirm the effective Kerr coefficient estimation of the hybrid structures. Spectral blue shift of the output pulse was observed in the slot-like graphene/silicon ridge waveguide. One possible explanation is that the blue shift was caused by the ultra-fast free carrier effect with the optical absorption of the doped graphene. This interesting effect can be used for soliton compression in femtosecond region. We also discussed the broadband anomalous dispersion of the Kerr coefficient of graphene.

(1)H NMR based metabolomics approach to study the toxic effects of dichlorvos on goldfish (Carassius auratus).

Dichlorvos (DDVP), one of the most widely used organophosphorus pesticides (OPs), has caused serious pollution in environment. In this study, (1)H nuclear magnetic resonance (NMR) based metabolomics approach combined with histopathological and immunohistochemical examination, and biochemical assays were used to investigate toxicities of DDVP on goldfish (Carassius auratus). After 10 days' exposure of DDVP at three dosages of 5.18, 2.59 and 1.73 mg/L, goldfish tissues (gill, brain, liver and kidney) and serum were collected. Histopathology revealed severe impairment of gills, livers and kidneys, and immunohistochemistry disclosed glial fibrillary acidic protein (GFAP) positive reactive astrocytes in brains. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles disclosed that DDVP influenced many metabolites (glutamate, aspartate, acetylcholine, 4-aminobutyrate, glutathione, AMP and lactate in brain; glutathione, glucose, histamine in liver; BCAAs, AMP, aspartate, glutamate, riboflavin in kidney) dose-dependently, involved with imbalance of neurotransmitters, oxidative stress, and disorders of energy and amino acid metabolism. Several self-protection mechanisms concerning glutamate degradation and glutathione (GSH) redox system were found in DDVP intoxicated goldfish.

Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09.

Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp. ZX09, and it is composed of only glucose monomers. The unique chemical composition and excellent physicochemical properties make Salecan a promising material for applications in coagulation, lubrication, protection against acute liver injury, and alleviating constipation. In this study, we cloned the Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without antibiotic selection, there was negligible loss of the plasmid in the host Agrobacterium sp. ZX09 after one passage of cultivation. The expression of Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by 30%. The other physiological changes included its elevated respiration rate and cellular invertase activity.

Tumoral cytotoxic and antioxidative phenylpropanoid glycosides in Smilax riparia A. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax riparia A. DC., known as "Niu-Wei-Cai" in China, is distributed through the south and middle of China. The roots and rhizomes of Smilax riparia have been used not only as traditional Chinese medicines (TCMs) for the treatment of bronchitis, lumbago of renal asthenia, traumatic injury, asthenia edema, and cancer but also as edible wild herbs in some areas of China. AIM OF THE STUDY: To identify the phytochemicals in the roots and rhizomes of Smilax riparia and to investigate their antioxidant activities and cytotoxicities toward several tumor cell lines. MATERIALS AND METHODS: Four fractions and five phenylpropanoid glycosides were obtained from roots and rhizomes of Smilax riparia under bioassay-guided screenings. The structures of five compounds were elucidated by spectroscopic methods and compared with published data. We evaluated their antioxidant activities and their cytotoxicities on five cancer cell lines: human promyelocytic leukemia (HL-60), human hepatocellular carcinoma (SMMC-7721), human lung cancer (A-549), human breast cancer (MCF-7), and human colon cancer (SW480). RESULTS: Of the five glycosides, one new compound (3, smilaside P) was isolated from an EtOAc fraction. Compound 1 was cytotoxic toward HL-60, SMMC-7721, A-549, MCF-7, and SW480 (IC50 2.70, 3.80, 11.91, 3.79, and 3.93 µM, respectively). Moreover, compounds 1-3 showed moderate scavenging activities against the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 339.58, 330.66, 314.49 µM, respectively). CONCLUSIONS: Five phenylpropanoid glycosides were reported for the first time from this TCM. Each was studied, as observed here for the first time, in the cytotoxic experiments toward HL-60, SMMC-7721, and SW480 cell lines. Compound 1, bearing three feruloyl groups and three acetyl groups, had the greatest cytotoxicity toward the five tumor cell lines. Compounds 1-3 showed moderate antioxidant activities. All results reflect that compounds 1-3 are cytotoxic for a wide variety of cancer cell lines of differing tissue origins and that the cytotoxicities of these compounds may be related to their antioxidant activities.

Adenosine induces G2/M cell-cycle arrest by inhibiting cell mitosis progression.

Cellular adenosine accumulates under stress conditions. Few papers on adenosine are concerned with its function in the cell cycle. The cell cycle is the essential mechanism by which all living things reproduce and the target machinery when cells encounter stresses, so it is necessary to examine the relationship between adenosine and the cell cycle. In the present study, adenosine was found to induce G-2/M cell-cycle arrest. Furthermore, adenosine was found to modulate the expression of some important proteins in the cell cycle, such as cyclin B and p21, and to inhibit the transition of metaphase to anaphase in mitosis.

Oral delivery of tumor-targeting Salmonella exhibits promising therapeutic efficacy and low toxicity.

Tumor-targeting bacteria have been developed as powerful anticancer agents. Salmonella typhimurium VNP20009, a representative tumor-targeting strain, has been systemically administered as a single-agent therapy at doses of 1 x 10(6) to 3 x 10(6) colony-forming unit (cfu)/mouse, or in combination with other antitumor agents at doses of 1 x 10(4) to 2 x 10(5) cfu/mouse. Recently, we reported that oral delivery of VNP20009 at the dose of 1 x 10(9) cfu/mouse induced significant anticancer effects comparable to that induced by systemic administration of this strain at 1 x 10(4) cfu/mouse. To further address the efficacy and safety of oral administration of bacteria, here we performed a systemically comparative analysis of anticancer efficacy and toxicity of VNP20009 administered: (i) orally at a dose of 1 x 10(9) cfu/mouse (VNP9-oral); (ii) intraperitoneally at a dose of 1 x 10(4) cfu/mouse (VNP4-i.p.); or (iii) intraperitoneally at a dose of 1 x 10(6) cfu/mouse in tumor-free and tumor-bearing murine models. The results showed that VNP9-oral, similar to VNP4-i.p., induced significant tumor growth inhibition whereas VNP6-i.p. induced better anticancer effect in the B16F10 melanoma model. Among three treatments, VNP9-oral induced the mildest and reversible toxicity whereas VNP6-i.p. resulted in the most serious and irreversible toxicities when compared to other two treatments. Moreover, the combination of VNP9-oral with a low dose of chemotherapeutics produced comparable antitumor effects but displayed significantly reduced toxicity when compared to VNP6-i.p. The findings demonstrated that oral administration, as a novel avenue in the application of bacteria, is highly safe and effective. Moreover, the present preclinical study should facilitate the optimization of bacterial therapies with improved anticancer efficacy and reduced adverse effects in future clinical trials.

Downregulation of survival signalling pathways and increased apoptosis in the transition of pressure overload-induced cardiac hypertrophy to heart failure.

1. Transition from compensated left ventricular (LV) hypertrophy to decompensated heart failure was characterized using a pressure-overload induced model to elucidate the temporal relationship between cardiomyocyte apoptosis and survival signalling in this transition. 2. Mice were subjected to transverse aortic constriction (TAC) or sham operation for 1-16 weeks and were studied by echocardiography, catheterization and histology. Relevant gene expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, Akt and glycogen synthase kinase (GSK)-3beta were determined. 3. Transverse aortic constriction resulted in myocyte hypertrophy and fibrosis from Week 4 and a progressive increase in left ventricular (LV) dimensions and wall thicknesses with maintained contractile function by Week 12. However, a sharp decline in contractile function and elevated LV end-diastolic pressure from 12 to 16 weeks were observed after TAC, indicating functional decompensation. 4. Following TAC, mRNA levels of atrial natriuretic peptide, B-type natriuretic peptide, beta-myosin heavy chain (MHC) and transforming growth factor-beta1 were increased time dependently, whereas mRNA expression of alpha-MHC, sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Bcl-2 were decreased. The ratio of Bcl-2/Bax was decreased and this was consistent with progressively increased myocyte apoptosis demonstrated by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling staining. Phosphorylation of ERK1/2 was increased by Week 4, but decreased thereafter. Levels of phosphorylated Akt declined from Week 8, whereas GSK3beta phosphorylation increased from 1 to 8 weeks, then decreased from Week 12 after TAC. 5. In conclusion, TAC resulted in early concentric and late eccentric hypertrophy with eventual development of LV dysfunction. This transition was temporally associated with a progressive increase in cell size, fibrosis and myocyte apoptosis. Downregulation of ERK1/2, Akt and GSK3beta and enhanced cardiomyocyte apoptosis are implicated as important mechanisms in the transition from compensated hypertrophy to heart failure.

[Ischemic postconditioning protects hypertrophic myocardium by ERK1/2 signaling pathway: experiment with mice].

OBJECTIVE: To investigate the effects of ischemic postconditioning (IPost) in protecting hypertrophic myocardium subjected to ischemic-reperfusion (I/R) and to study the role of extracellular regulated protein kinase (ERK1/2) in mediating such protection. METHODS: Transverse aortic constriction (TAC) operation was performed on 12-week-old C57/BL mice to establish left ventricular hypertrophy models. Sixty-four isolated TAC mouse hearts were mounted onto the Langendorff perfusion system and randomly divided into 4 equal group: (1) I/R group undergoing stable perfusion for 30 min, ischemia for 30 min, and re-perfusion for 120 min (an I/R cycle) to cause hypertrophic myocardium I/R injury, (2) IPost group undergoing ischemia for 10s and reperfusion for 10s, totally 3 cycles (60s) before reperfusion for 120 min, (3) I/R+ PD98059 (an ERK1/2 inhibitor) group undergoing perfusion of Krebs-Henseleit (KH) buffer with PD98059 10(-5)mol/L for 15 min and perfusion of KH buffer without PD98059 at the beginning of re-perfusion, and (4) IPost + PD98059 group undergoing 3 cycles of IPost and perfusion of KH buffer with PD98059 10(-5)mol/L for 15 min at the beginning of re-perfusion. Hemodynamic examination was conducted 120 min after re-perfusion to measure the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal uprising velocity of left ventricle pressure (dp/dt(max)), and minimal uprising velocity of left ventricle pressure (dp/dt(min)). After the I/R procedure the myocardium of the left ventricle was isolated to detect the infarction size (IS). Western blotting was used to detect the protein expression of extracellular signal-regulated kinase (ERK) 1/2, phosphorylated ERK1/2, Bcl-2, Bax, and mitochondrial and cytosolic cytochrome (Cyt). C. TUNEL was used to detect the apoptotic rate. RESULTS: The LVSP and dp/dt(max) levels of the IPost group were (85 +/- 4) mm Hg and (3811 +/- 230) mm Hg/s, both significantly higher than those of the I/R group [(68 +/- 5) mm Hg and (2830 +/- 230) mm Hg/s respectively, both P < 0.05]. Compared with the I/R group, the protein levels of phosphorylated ERK1/2, Bcl-2, mitochondrial CytC of the IPost group were all significantly higher, the protein levels of Bax and cytosolic CytC, and apoptosis index were significantly lower (all P < 0.05), and the IS was smaller (P < 0.05). I/R + PD98059 showed no effects on the above-mentioned parameters. However, the results of the IPost + PD98059 group showed that in the first 15 min of reperfusion addition of PD98059 reversed all changes observed in the IPost group and eliminated the IPost protection by increasing IS to a level similar to that in the I/R group. CONCLUSION: IPost has protective effect in hypertrophic myocardium with I/R injury in vitro. ERK1/2 signaling pathway is involved in the protection of IPost by regulating the myocyte apoptosis.

[Effects of ischemia postconditioning on ischemia-reperfusion injury and reperfusion injury salvage kinase signal transduction pathways in isolated mouse hearts].

OBJECTIVE: To explore the effects of ischemia postconditioning (IPC) on ischemia-reperfusion (I/R) injury and associated reperfusion injury salvage kinase (RISK) signal transduction pathways changes in isolated mouse hearts. METHODS: Langendorff perfused C57/BL mouse hearts were divided to 6 groups: (1) control: 30 min global ischemia and 2 h reperfusion (I/R); (2) IPC with 3 episodes, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (3) IPC with 6 episodes, IPC with six episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (4) delayed IPC, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and at one minute after reperfusion; (5) IPC + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min); (6) I/R + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min). The effects of IPC on hemodynamics, coronary artery flow, creatine kinase (CK) and lactate dehydrogenase (LDH) release, myocardial SOD, MDA, phospho-protein kinase (P-ERK1/2) and phospho-protein kinase B (P-Akt) as well as myocardial infarction size were measured. RESULTS: IPC with 3 episodes and IPC with 6 episodes significantly and equally improved myocardial function, increased myocardial SOD, reduced CK and LDH release and myocardial infarction size compared with IR group (all P < 0.01) while these parameters were similar between I/R hearts and delayed IPC hearts. IPC significantly increased myocardial ERK1/2 phosphorylation, PD98059 inhibited the phosphorylation of ERK1/2 and abolished the cardioprotective effects induced by IPC. CONCLUSIONS: IPC obviously attenuated I/R injury in isolated mouse hearts, the cardioprotection of IPC was not enhanced because of increasing of IPC episodes and disappeared in delayed IPC. The cardioprotective effects of IPC were mediated through ERK1/2-MAPK signal transduction pathway.

Percutaneous transcatheter closure of patent ductus arteriosus with an amplatzer duct occluder using retrograde guidewire-established femoral arteriovenous loop.

1. The traditional antegrade wire-guided percutaneous transcatheter approach is not ideal in closing some types of patent ductus arteriosus (PDA) with abnormal morphology. The aim of the present study was to evaluate the efficacy of a retrograde wire-guided transcatheter approach for closure of some types of PDA using the Amplatzer duct occluder (ADO). 2. Nineteen patients with abnormal PDA morphology, including a smaller ostium of the side of the pulmonary artery compared with the side of the descending aorta, severe calcification or tortuosity, were included in the present study. In these patients, after the antegrade approach failed to cross a wire from the pulmonary artery via the PDA to the descending aorta, a retrograde guidewire was passed through the PDA in the opposite direction, from the descending aorta to the pulmonary artery, to establish a femoral arteriovenous loop that assisted the deployment of the ADO in all 19 patients. The size of the PDA, as determined by angiography, was 3.1 +/- 1.1 mm and the diameter of the ADO selected was 6.5 +/- 1.5 mm. 3. In 16 cases, systolic murmur disappeared after the procedure. Systolic murmur (less than Grade II) and angiographic residual shunt remained in three cases immediately after the procedure, but disappeared 1 month later. Mean pulmonary arterial pressure decreased from 33 +/- 8 to 22 +/- 4 mmHg in all 19 patients (P < 0.01). There were no complications during or after the procedure. 4. The retrograde wire-guided technique offers an alternative approach to facilitate closure of a PDA that cannot be achieved by traditional antegrade wire-guided methods due to morphological abnormalities in the PDA.

[The effect of Chinese medicine yiqihuoxuetang on T-lymphocyte subpopulation in peripheral blood of infertile men with antisperm antibodies].

OBJECTIVES: To study whether Chinese Medicine Yiqihuoxuetang(YQHXT) could inhibit antisperm antibodies in infertile men, and to explore the therapeutical mechanism of YQHXT. METHODS: Thirty infertile men with antisperm antibodies took YQHXT continuously for 60 days. Indirect immuno-fluorescence technique (IFT) was used to detect the levels of CD3, CD4, CD8 and CD4/CD8 ratio before and after treatment. RESULTS: CD4 value and CD4/CD8 ratio after treatment were significantly lower than before treatment (P < 0.05); CD8 value became significantly higher(P < 0.05). CONCLUSIONS: The results indicated that YQHXT could inhibit antisperm antibodies by keeping the balance of T-lymphocyte subpopulation in immunoinfertile men.