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Find video protocols related to scientific articles indexed in Pubmed.
Total Synthesis of 6-Deoxypladienolide D and Assessment of Splicing Inhibitory Activity in a Mutant SF3B1 Cancer Cell Line.
Org. Lett.
PUBLISHED: 10-26-2014
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A total synthesis of the natural product 6-deoxypladienolide D (1) has been achieved. Two noteworthy attributes of the synthesis are (1) a late-stage allylic oxidation which proceeds with full chemo-, regio-, and diastereoselectivity and (2) the development of a scalable and cost-effective synthetic route to support drug discovery efforts. 6-Deoxypladienolide D (1) demonstrates potent growth inhibition in a mutant SF3B1 cancer cell line, high binding affinity to the SF3b complex, and inhibition of pre-mRNA splicing.
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[Metabolic pathway and metabolites of total diterpene acid isolated from Pseudolarix kaempferi].
Yao Xue Xue Bao
PUBLISHED: 10-18-2014
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The preliminary metabolic profile of total diterpene acid (TDA) isolated from Pseudolarix kaempferi was investigated by using in vivo and in vitro tests. Pseudolaric acid C2 (PC2) was identified as the predominant metabolite in plasma, urine, bile and feces after both oral and intravenous administrations to rats using HPLC-UV and HPLC-ESI/MS(n), and demethoxydeacetoxypseudolaric acid B (DDPB), a metabolite proposed to be the glucoside of PC2 (PC2G), as well as pseudolaric acid C (PC), pseudolaric acid A (PA), pseudolaric acid A O-beta-D glucopyranoside (PAG), pseudolaric acid B O-beta-D glucopyranoside (PBG) and deacetylpseudolaric acid A (DPA) originated from TDA could also be detected. It was demonstrated by tests that the metabolism of TDA is independent of intestinal microflora, and neither of pepsin and trypsin is in charge of metabolism of TDA, TDA is also stable in both pH environments of gastric tract and intestinal tract. The metabolites of TDA in whole blood in vitro incubation were found to be PC2, DDPB and PC2G, which demonstrated that the metabolic reaction of TDA in vivo is mainly occurred in blood and contributed to be the hydrolysis of plasma esterase to ester bond, as well as the glucosylation reaction. These results clarified the metabolic pathway of TDA for the first time, which is of great significance to the in vivo active form and acting mechanism research of P. kaempferi.
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Regulation of histone acetyltransferase TIP60 function by histone deacetylase 3.
J. Biol. Chem.
PUBLISHED: 10-11-2014
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The key member of the MYST acetyltransferases family, TIP60 (Tat-interactive protein, 60KD) tightly modulates a wide array of cellular processes, including chromatin remodeling, gene transcription, apoptosis, DNA repair and cell cycle arrest. The function of TIP60 can be regulated by SIRT1 through deacetylation. Here, we found that TIP60 can also be functionally regulated by HDAC3. We identified six lysine residuals as its autoacetylation sites. Mutagenesis of these lysines to arginines completely abolishes the autoacetylation of TIP60. Overexpression of HDAC3 increases TIP60 ubiquitination levels. However, unlike SIRT1, HDAC3 increased the half-life of TIP60. Further study found that HDAC3 co-localized with TIP60 both in the nucleus and the cytoplasm which could be the reason that HDAC3 can stabilize the TIP60. The deacetylation of TIP60 by both SIRT1 and HDAC3 reduces apoptosis induced by DNA damage. Knockdown of HDAC3 in cells increased TIP60 acetylation levels and increased apoptosis after DNA damage. Together, our findings provide a better understanding of TIP60 regulation mechanisms which is significant basis for further studies on its cellular functions.
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Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives.
J Asian Nat Prod Res
PUBLISHED: 10-08-2014
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In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification.
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[Comparison of paravertebral soft tissue tension changes in patients with chronic lower back pain treated by sliver needle and traditional Chinese medicine fumigation].
Zhongguo Gu Shang
PUBLISHED: 09-23-2014
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To evaluate clinical significance of waist soft tissue tension detection in treating chronic nonspecific low back pain.
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The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.
BMJ Open
PUBLISHED: 09-19-2014
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The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer.
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Clinical applications of the indirect immunofluorescence assay for detection of anti-cell membrane-associated DNA antibodies in Juvenile Systemic Lupus Erythematosus.
Pediatr. Res.
PUBLISHED: 08-15-2014
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BackgroundJuvenile-onset systemic lupus erythematosus (JSLE) has a higher mortality risk compared to adult-onset SLE. We compared the diagnostic value of anti-cmDNA antibodies with that of anti-nucleosome antibodies (AnuA), anti-Sm antibodies and anti-dsDNA antibodies and human B lymphocyte Raji cells with that of human promyelocytic leukemia HL60 cells as substrates in an indirect immunofluorescence assay to detect anti-cmDNA antibodies in JSLE patients.MethodsWe recruited 92 JSLE patients and 71 patients with other rheumatic diseases. Anti-cmDNA antibodies and ANA were detected in patient sera using indirect immunofluorescence assays. Anti-dsDNA antibodies were detected by combining ELISA and indirect immunofluorescence. Anti-Sm antibodies were detected by double immunodiffusion assay and immunoblotting, while anti-nucleosome antibodies (AnuA) were detected by ELISA.ResultsJSLE group had a significantly higher percentage of patients positive for anti-cmDNA compared to patients with other rheumatoid diseases. Using one antibody for diagnosis, anti-cm DNA antibodies has highest accuracy as 84.0%, using 2 antibodies, the combination of anti-cm DNA and anti-dsDNA antibodies has 90.8 % accuracy. Raji cells used as substrate demonstrated a stronger intensity of fluorescent patterns compared to HL60 cells.ConclusionThe high sensitivity, specificity and accuracy of detection of anti-cmDNA antibodies make it a valuable diagnostic tool for JSLE.Pediatric Research (2014); doi:10.1038/pr.2014.182.
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Association of the interleukin-22 genetic polymorphisms with ulcerative colitis.
Diagn Pathol
PUBLISHED: 08-08-2014
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Interleukin-22 (IL-22) is a member of the IL-10 family of anti-inflammatory cytokines that mediates epithelial immunity. IL-22 expression was found to be increased in patients with ulcerative colitis (UC). Whether genetic polymorphisms of IL-22 also influence UC risk is still unknown. The purpose of this study was to investigate the association between the IL-22 gene polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) and the risk of UC in Chinese Han patients.
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Development and application of an AllGlo probe-based qPCR assay for detecting knockdown resistance (kdr) mutations in Anopheles sinensis.
Malar. J.
PUBLISHED: 07-16-2014
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Anopheles sinensis is one of the most important malaria vectors in China and other Southeast Asian countries. High levels of resistance have been reported in this species due to the long-term use of insecticides, especially pyrethroids, for public health and agricultural purposes. Knockdown resistance (kdr) caused by a single base pair mutation in the gene encoding the sodium channel is strongly associated with pyrethroid insecticide resistance in many Anopheles mosquitoes. There are few methods currently available for detecting kdr mutations in An. sinensis.
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Inhibition of TNF-? in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats.
Toxicol. Appl. Pharmacol.
PUBLISHED: 07-12-2014
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We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-?) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-?B (NF-?B) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-? blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (?-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-?B p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-? in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-?B p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy.
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Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-09-2014
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In mammalian cells, tumor suppressor p53 plays critical roles in the regulation of glucose metabolism, including glycolysis and oxidative phosphorylation, but whether and how p53 also regulates gluconeogenesis is less clear. Here, we report that p53 efficiently down-regulates the expression of phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), which encode rate-limiting enzymes in gluconeogenesis. Cell-based assays demonstrate the p53-dependent nuclear exclusion of forkhead box protein O1 (FoxO1), a key transcription factor that mediates activation of PCK1 and G6PC, with consequent alleviation of FoxO1-dependent gluconeogenesis. Further mechanistic studies show that p53 directly activates expression of the NAD(+)-dependent histone deacetylase sirtuin 6 (SIRT6), whose interaction with FoxO1 leads to FoxO1 deacetylation and export to the cytoplasm. In support of these observations, p53-mediated FoxO1 nuclear exclusion, down-regulation of PCK1 and G6PC expression, and regulation of glucose levels were confirmed in C57BL/J6 mice and in liver-specific Sirt6 conditional knockout mice. Our results provide insights into mechanisms of metabolism-related p53 functions that may be relevant to tumor suppression.
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Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and ?-amino butyric acid in hypertensive rats.
Exp. Biol. Med. (Maywood)
PUBLISHED: 05-28-2014
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Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25?pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or ?-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats.
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[Experimental observation of toxic effect of Bacillus thuringiensis var. israelensis against Aedes, Culex and Anopheles larvae].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 05-08-2014
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To evaluate the toxic effect of Bacillus thuringiensis var. israelensis (Bti) wettable powder against Aedes, Culex and Anopheles larvae.
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Terahertz pulsed spectroscopy of paraffin-embedded brain glioma.
J Biomed Opt
PUBLISHED: 04-11-2014
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The refractive indices, absorption coefficients, and complex dielectric constants of paraffin-embedded brain glioma and normal brain tissues have been measured by a terahertz time-domain spectroscopy (THz-TDS) system in the 0.2- to 2.0-THz range. The spectral differences between gliomas and normal brain tissues were obtained. Compared with normal brain tissue, our results indicate that paraffin-embedded brain gliomas have a higher refractive index, absorption coefficient, and dielectric constant. Based on these results, the best THz frequencies for different methods of paraffin-embedded brain glioma imaging, such as intensity imaging, coherent imaging with continuum THz sources, and THz pulsed imaging with short-pulsed THz sources, are analyzed.
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Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.
Neuroscience
PUBLISHED: 04-08-2014
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Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases.
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Transneuronal tracing of central autonomic regions involved in cardiac sympathetic afferent reflex in rats.
J. Neurol. Sci.
PUBLISHED: 03-25-2014
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Stimulation of cardiac afferents (CA) increased sympathetic outflow and blood pressure. The goal of the current study is to determine the central autonomic nuclei involved in the regulation of cardiac sympathetic afferent reflex (CSAR) which has been proved in previously functional studies. Neuroanatomical method and pseudorabies virus (PRV) transynaptic retrograde trace technique will be performed to investigate the relationship between kidney and heart and the temporal order of the most PRV-labeled neurons in the central nervous system. Recombinant PRV expressing enhanced green fluorescence protein (EGFP) was injected into the left kidney of rats as a specific trans-synaptic retrograde tracer in neurons. After 2, 3, 4, 5, 6, 7, 8 or 9 days, brain, spinal cord and heart were collected for immunofluorescence staining. The temporal order of PRV labeled neurons was found in the ipsilateral intermediolateral nucleus (IML) of T8-T12 spinal segments on day 3; bilateral rostroventrolateral medulla (RVLM), paraventricular nucleus (PVN) and nucleus of the solitary tract (NTS) on day 4; and left and right ventricular walls and ventricular septum of the heart on day 9. In rats with renal denervation, no PRV-infected neurons or cardiomyocytes were found after PRV injection. In conclusion, PRV trans-synaptic retrograde trace confirms that CA, NTS, PVN, RVLM, IML and renal nerves do exist to be involved in the regulation of CSAR and there is a close relationship between heart and kidney. CA is mainly located in the left ventricular wall, right ventricular wall and ventricular septum.
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Salusin-? in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats.
J. Hypertens.
PUBLISHED: 03-14-2014
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Rostral ventrolateral medulla (RVLM) plays crucial roles in central cardiovascular regulation. Salusin-? is a multifunctional bioactive peptide and is expressed in the brain and various peripheral tissues. The present study was designed to identify the expression of salusin-? in the RVLM, and to determine its roles and mechanisms in regulating sympathetic outflow and blood pressure in hypertension.
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Ratiometric near-infrared chemosensor for trivalent chromium ion based on tricarboyanine in living cells.
Anal. Chim. Acta
PUBLISHED: 03-13-2014
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A tricarboyanine derivative (IRPP) is applied as a ratiometric near-infrared chemosensor for detecting trivalent chromium ions (Cr(3+)) in living cells. Upon the addition of Cr(3+) to a solution of IRPP, large-scale shifts in the emission spectrum (from 755 nm to 561 nm) are observed. In the newly developed sensing system, these well-resolved emission peaks yield a sensing system that covers a linear range from 1.0×10(-7) to 1.0×10(-5) M with a detection limit of 2.5×10(-8) M. The experimental results show the response behavior of IRPP towards Cr(3+) is pH independent under neutral conditions (6.0-7.5). Most importantly, the fast response time (less than 3 min) and selectivity for Cr(3+) over other common metal ions provide a strong argument for the use of this sensor in real world applications. As a proof of concept, the proposed chemosensor has been used to detect and quantify Cr(3+) in river water samples and to image Cr(3+) in living cells with encouraging results.
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Synthesis and biological evaluation of novel trichodermin derivatives as antifungal agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-10-2014
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To discover more potential antifungal agents, 17 novel trichodermin derivatives were designed and synthesized by modification of 3 and 4a. The structures of all the synthesized compounds were confirmed by (1)H NMR, ESI-MS and HRMS. Their antifungal activities against Ustilaginoidea oryzae and Pyricularia oryzae were evaluated. Most of the target compounds showed potent inhibitory activity, in which 4g showed superior inhibitory effects than 4a and commercial fungicide prochloraz. Furthermore, 4h demonstrated comparable inhibitory activity to 4a. Moreover, 4i and 4l exhibited excellent inhibitory activity for Pyricularia oryzae. Additionally, compound 9 was found to be more active against all tested fungal strains than 3, with EC50 values of 0.47 and 3.71 mg L(-1), respectively.
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[Assessment of RBC transfusion volume and its effect on postoperative pulmonary complications in on-pump CABG patients].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 03-07-2014
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This study was purposed to investigate the effect of the transfused RBC amount on pulmonary complications after on-pump CABG surgery, and to explore the influencing factors on RBC transfusion volume. 292 adult patients receiving on-pump CABG surgery were divided into non-RBC transfusion group (n = 71), 1-4 U RBC transfusion group (n = 144) and >4 U RBC transfusion group (n = 77). Adjusted multivariable regression analysis was performed to examine the correlation between transfused RBC amount and the odds of pulmonary complications, and multivariable linear regression was used to analyze the influencing factors on RBC transfusion volume. The results showed that compared the three groups, there was the significant difference in postoperative pulmonary complications (1.4% vs 14.6% vs 24.7%, P < 0.001). A stronger and graded correlation was found between transfused RBC amount and pulmonary complications in on-pump CABG patients, the adjusted odds were increased to 1.251 (95% CI: 1.120-1.398, P < 0.001), and influencing factors on RBC transfusion volume were as follows: age (B:0.102; 95% CI: 0.046-0.157, P < 0.001), sex (B:1.825; 95% CI: 0.692-2.957, P = 0.002), preoperative Hct (B:-36.044; 95% CI:-47.724--25.163, P < 0.001), CPB time (B: 0.031; 95% CI:0.013-0.050, P = 0.001) and acute myocardiac infarction (B:2.769; 95% CI: 1.295-4.243, P < 0.001). It is concluded that the transfused RBC amount is related with postoperative pulmonary complications, and the influencing factors on RBC transfusion volume include preoperative Hct, age, acute myocardiac infarction, sex and CPB time.
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Inhaled Budesonide Prevents Acute Mountain Sickness in Young Chinese Men.
J Emerg Med
PUBLISHED: 03-03-2014
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Oral glucocorticoids can prevent acute mountain sickness (AMS). Whether inhaled budesonide (BUD) can prevent AMS remains unknown.
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Disruption of zebrafish (Danio rerio) sexual development after full life-cycle exposure to environmental levels of triadimefon.
Environ. Toxicol. Pharmacol.
PUBLISHED: 02-18-2014
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In this study, zebrafish was exposed to environmental levels of triadimefon (0.125, 0.25, 0.5 ?g/mL) from 24 h post fertilization to 120 days post fertilization. Several endpoints that related to reproductive function were evaluated. It was found that the body length, body weight and vitellogenin transcription were significantly reduced for fish exposed to triadimefon. Histological examination showed that the sex ratio of fish skewed to male and female exposed to 0.5 ?g/mL triadimefon had immature ovary. The breeding success, as determined from data on egg production and spawning, was reduced in fish exposed to 0.25 ?g/mL triadimefon. In the offspring, the reduced egg fertility, hatching rate and survival were observed in eggs exposed to 0.5 ?g/mL triadimefon. These findings indicated that triadimefon had the potential to adversely affect the sexual development and breeding success through the multiple endocrine actions.
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Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry.
J Sep Sci
PUBLISHED: 02-14-2014
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This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 ?g/kg. The precision for determining the quinolones was <19.39%. The proposed method was successfully developed for the determination of quinolones in real cosmetic samples.
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Inhaled budesonide and oral dexamethasone prevent acute mountain sickness.
Am. J. Med.
PUBLISHED: 02-13-2014
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This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure.
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Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension.
Toxicol. Appl. Pharmacol.
PUBLISHED: 02-06-2014
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To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension.
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Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension.
Toxicol. Appl. Pharmacol.
PUBLISHED: 02-02-2014
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The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10?g/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.
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Control strategies for effective robot assisted gait rehabilitation: The state of art and future prospects.
Med Eng Phys
PUBLISHED: 01-31-2014
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A large number of gait rehabilitation robots, together with a variety of control strategies, have been developed and evaluated during the last decade. Initially, control strategies applied to rehabilitation robots were adapted from those applied to traditional industrial robots. However, these strategies cannot optimise effectiveness of gait rehabilitation. As a result, researchers have been investigating control strategies tailored for the needs of rehabilitation. Among these control strategies, assisted-as-needed (AAN) control is one of the most popular research topics in this field. AAN training strategies have gained the theoretical and practical evidence based backup from motor learning principles and clinical studies. Various approaches to AAN training have been proposed and investigated by research groups all around the world. This article presents a review on control algorithms of gait rehabilitation robots to summarise related knowledge and investigate potential trends of development. There are existing review papers on control strategies of rehabilitation robots. The review by Marchal-Crespo and Reinkensmeyer (2009) had a broad cover of control strategies of all kinds of rehabilitation robots. Hussain et al. (2011) had specifically focused on treadmill gait training robots and covered a limited number of control implementations on them. This review article encompasses more detailed information on control strategies for robot assisted gait rehabilitation, but is not limited to treadmill based training. It also investigates the potential to further develop assist-as-needed gait training based on assessments of patients' ability. In this paper, control strategies are generally divided into the trajectory tracking control and AAN control. The review covers these two basic categories, as well as other control algorithm and technologies derived from them, such as biofeedback control. Assessments on human gait ability are also included to investigate how to further develop implementations based on assist-as-needed concept. For the consideration of effectiveness, clinical studies on robotic gait rehabilitation are reviewed and analysed from the viewpoint of control algorithm.
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New oleanane-type triterpenoid saponins isolated from the seeds of Celosia argentea.
J Asian Nat Prod Res
PUBLISHED: 01-25-2014
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Three new oleanane-type triterpenoid saponins named celosins H, I, and J were isolated from the seeds of Celosia argentea L. Their structures were characterized as 3-O-?-D-xylopyranosyl-(1 ? 3)-?-D-glucuronopyranosyl-polygalagenin 28-O-?-D-glucopyranosyl ester, 3-O-?-D-glucuronopyranosyl-medicagenic acid 28-O-?-D-xylcopyranosyl-(1 ? 4)-?-L-rhamnopyranosyl-(1 ? 2)-?-D-fucopyranosyl ester, and 3-O-?-D-glucuronopyranosyl-medicagenic acid 28-O-?-L-arabinopyranosyl-(1 ? 3)-[?-D-xylcopyranosyl-(1 ? 4)]-?-L-rhamnopyranosyl-(1 ? 2)-?-D-fucopyranosyl ester by NMR, MS, and chemical evidences, respectively. In our opinion, celosins H-J could be used as chemical markers for the quality control of C. argentea seeds.
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Reconstruction of Wide-apart Double Defect Using a Branch-based Chimeric Anterolateral Thigh Flap.
Plast Reconstr Surg Glob Open
PUBLISHED: 01-01-2014
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Wide-apart double defect in head and neck region is rare and difficult to reconstruct at one time. Double free flaps are normally used for this scenario and often tedious and technically complicated. This study presented a technique using branch-based anterolateral thigh free flap to simultaneously reconstruct the 2 defects separated wide apart. The concept, indications, surgical technique, and anatomical variations are discussed. Branch-based anterolateral thigh flap is a safe technique and the dissection will be easy when the oblique branch is present.
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Targeting histone deacetylases for cancer therapy: from molecular mechanisms to clinical implications.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, studies over the past decades have demonstrated that epigenetic regulation also participates in the development of cancer. The fundamental patterns of epigenetic components, such as DNA methylation and histone modifications, are frequently altered in tumor cells. Acetylation is one of the best characterized modifications of histones, which is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are a group of enzymes which catalyze the removal of the acetyl groups of both histones and non-histone proteins. HDACs are involved in modulating most key cellular processes, including transcriptional regulation, apoptosis, DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors are being investigated to act as cancer chemotherapeutics. The primary purpose of this paper is to summarize recent studies of the links between HDACs and cancer, and further discuss the underlying mechanisms of anti-tumor activities of HDAC inhibitors and clinical implications.
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Notch-1 and Ki-67 receptor as predictors for the recurrence and prognosis of Kimura's disease.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Kimura's disease (KD) is a rare chronic disease with unknown origin. It remains controversial in KD's diagnosis, treatment, transformation and need further research. The aim of this study is to investigate the clinicopathologic features of KD and the relationship between the expression of Notch-1, Ki-67 receptor and the recurrence of KD. The hematoxylin and eosin sections and clinical data of 40 patients diagnosed with KD were examined retrospectively. Specimens were available in these 40 cases. Notch-1 and Ki-67 expression were examined using IHC (immunohistochemistry staining) analysis. Of 40 cases of KD (average age, 38.4 years; median age, 36.0 years), 34 cases (85.0%) were clinically seen to involve swelling of the head and neck region. Notch-1 and Ki-67 have a high expression in recurrent patients. High expression of Notch-1 receptor and Ki-67 tended to be found in patients who relapsed. This is the first study to discuss the correlation among Notch-1, Ki-67 and recurrent KD. These results suggest both of the markers may act as promising predictors for the recurrence and prognosis of KD. However, Notch-1 immunoexpression had no statistically significant association with the Ki-67 proliferation index.
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Exercise training attenuates hypertension and cardiac hypertrophy by modulating neurotransmitters and cytokines in hypothalamic paraventricular nucleus.
PLoS ONE
PUBLISHED: 01-01-2014
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Regular exercise as an effective non-pharmacological antihypertensive therapy is beneficial for prevention and control of hypertension, but the central mechanisms are unclear. In this study, we hypothesized that chronic exercise training (ExT) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and restoring the neurotransmitters balance in the hypothalamic paraventricular nucleus (PVN) in young spontaneously hypertensive rats (SHR). In addition, we also investigated the involvement of nuclear factor-?B (NF-?B) p65 and NAD(P)H oxidase in exercise-induced effects.
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[Molluscicidal effect of plastic film mulch covering method].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 12-24-2013
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To evaluate the molluscicidal effect of the plastic film mulch covering method.
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Histological study of chordoma origin from fetal notochordal cell rests.
Spine
PUBLISHED: 12-04-2013
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The histological comparative study was performed on chordoma and notochordal cell rests (NCRs).
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Intermedin in Paraventricular Nucleus Attenuates Sympathetic Activity and Blood Pressure via Nitric Oxide in Hypertensive Rats.
Hypertension
PUBLISHED: 11-11-2013
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Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N(?)-propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride. AM22-52 increased renal sympathetic nerve activity and mean arterial pressure in 2K1C rats but not in sham-operated rats, whereas calcitonin/calcitonin gene-related peptide receptor antagonist calcitonin/calcitonin gene-related peptide 8-37 had no significant effect. CRLR and RAMP3 mRNA, as well as CRLR, RAMP2, and RAMP3 protein expressions, in the PVN were increased in 2K1C rats. Microinjection of IMD into the PVN increased the NO metabolites (NOx) level in the PVN in 2K1C rats, which was prevented by AM22-52. Chronic PVN infusion of IMD reduced, but AM22-52 increased, blood pressure in conscious 2K1C rats. These results indicate that IMD in the PVN inhibits sympathetic activity and attenuates hypertension in 2K1C rats, which are mediated by adrenomedullin receptors (CRLR/RAMP2 or CRLR/RAMP3) and its downstream NO.
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[A randomized controlled trial of intensity-modulated radiation therapy plus docetaxel and cisplatin versus simple intensity-modulated radiation therapy in II(-III( stage esophageal carcinoma].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 09-25-2013
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To compare the efficacy and toxicity of intensity- modulated radiation therapy plus chemotherapy(IMRT-TP) with simple intensity-modulated radiation therapy(IMRT) in the treatment of locally advanced esophageal carcinoma.
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[Research progress on malaria vector control].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
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Vector control plays a crucial role in the stages of malaria control and elimination. Currently, it mainly relies on the chemical control methods for adult mosquitoes in malaria endemic areas, however, it is undergoing the serious threat by insecticide resistance. In recent years, the transgenic technologies of malaria vectors have made a great progress in the laboratory. This paper reviews the challenges of the traditional methods and the rapid developed genetic modified technology in the application of vector control.
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[Deltamethrin resistance, metabolic detoxification enzyme and kdr mutation in Anopheles sinensis in region along Huaihe River in Anhui Province].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
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To understand the deltamethrin resistance level, GTS and P450 metabolic detoxification enzyme activities, and mutations in the para-type sodium channel gene that confers knockdown resistance (kdr) in Anopheles sinensis mosquitoes from malaria endemic areas along the Huaihe River in Anhui Province, China.
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Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-27-2013
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The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5?g/h) or vehicle for 4weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1? and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy.
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Systematic identification of Class I HDAC substrates.
Brief. Bioinformatics
PUBLISHED: 08-23-2013
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Lysine acetylation is a common post-translational modification of histone and non-histone proteins. This process has an important function in regulating transcriptional activities and other biological processes. Although several computer programs have been developed to predict protein acetylation sites, deacetylases responsible for known or predicted acetylation sites remain unknown. In this research, Class I histone deacetylases (HDACs) substrates were manually obtained, and sequence features of deacetylation sites were analyzed. We found that three members of Class I HDACs (HDAC1, HDAC2 and HDAC3) shared similar sequence features. Therefore, a method was proposed to identify the substrates of Class I HDACs. We evaluated the efficiency of the prediction based on P-value distribution analysis and leave-one-out test. To validate the result of the prediction, we overexpressed Class I HDACs in cells and detected the acetylation levels of potential substrates. In the experiment, five of the seven predicted proteins were deacetylated by Class I HDACs. These results suggested that our method could effectively predict protein deacetylation sites. The work has been integrated to the website ASEB, which was freely available at http://cmbi.bjmu.edu.cn/huac.
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[Influence on AM fungi infection rate and medicine quality of Pinellia ternata in condition of three soil impact factors].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-16-2013
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To explore the influence on AM fungi infection rate and medicine quality of Pinellia ternate in the condition of three soil impact factors.
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[Study on TaqMan-MGB real-time fluorescence quantitative PCR to detect gene mutation of kdr from Anopheles sinensis].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 07-31-2013
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To establish a Real-time Fluorescence Quantitative PCR to detect the kdr gene mutation in Anopheles sinensis.
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[Laryngeal reconstruction by complex hyoid bone flap after frontal partial laryngectomy].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 07-27-2013
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The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome.
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[Analysis of risk factors for spontaneous rupture of hepatocellular carcinoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 07-25-2013
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To assess the risk factors for spontaneous rupture of hepatocellular carcinoma (SRHC).
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Interaction Between AT1 Receptor and NF-?B in Hypothalamic Paraventricular Nucleus Contributes to Oxidative Stress and Sympathoexcitation by Modulating Neurotransmitters in Heart Failure.
Cardiovasc. Toxicol.
PUBLISHED: 07-24-2013
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Angiotensin II type 1 receptor (AT1-R) and nuclear factor-kappaB (NF-?B) in the paraventricular nucleus (PVN) play important roles in heart failure (HF); however, the central mechanisms by which AT1-R and NF-?B contribute to sympathoexcitation in HF are yet unclear. In this study, we determined whether interaction between AT1-R and NF-?B in the PVN modulates neurotransmitters and contributes to NAD(P)H oxidase-dependent oxidative stress and sympathoexcitation in HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary artery ligation or sham surgery (SHAM). Subsequently, animals were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS, 10 ?g/h), an AT1-R antagonist; or pyrrolidine dithiocarbamate (PDTC, 5 ?g/h), a NF-?B inhibitor via osmotic minipump. Myocardial infarction (MI) rats had higher levels of glutamate (Glu), norepinephrine (NE) and NF-?B p65 activity, lower levels of gamma-aminobutyric acid (GABA), and more positive neurons for phosphorylated IKK? and gp91(phox) (a subunit of NAD(P)H oxidase) in the PVN when compared to SHAM rats. MI rats also had higher levels of renal sympathetic nerve activity (RSNA) and plasma proinflammatory cytokines (PICs), NE and epinephrine. PVN infusions of LOS or PDTC attenuated the decreases in GABA and the increases in gp91(phox), NF-?B activity, Glu and NE, in the PVN of HF rats. PVN infusions of LOS or PDTC also attenuated the increases in RSNA and plasma PICs, NE and epinephrine in MI rats. These findings suggest that interaction between AT1 receptor and NF-?B in the PVN contributes to oxidative stress and sympathoexcitation by modulating neurotransmitters in heart failure.
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Comparison of efficacy for postoperative chemotherapy and concurrent radiochemotherapy in patients with IIIA-pN2 non-small cell lung cancer: An early closed randomized controlled trial.
Radiother Oncol
PUBLISHED: 06-10-2013
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The efficacy of postoperative concurrent radiochemotherapy (POCRT) on IIIA-pN2 non-small cell lung cancer (NSCLC) is still unclear. The aim of this randomized controlled trial was to compare POCRT with postoperative chemotherapy (POCT) alone in terms of survival and relapse patterns.
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Sentinel lymph node biopsy versus elective neck dissection in patients with cT1-2N0 oral tongue squamous cell carcinoma.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 06-09-2013
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This study aimed to compare the value of sentinel lymph node biopsy (SLNB) with that of elective neck dissection (END) for the prediction of cervical lymph node metastasis in patients with clinically diagnosed T1-2N0 (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC), and it aimed to examine the prognostic value of individualized treatment in sentinel lymph node (SLN)-negative patients.
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Simultaneous determination of eleven flavonoid glycosides in ginkgo biloba leaves collected in different seasons by UPLC PDA method.
Yao Xue Xue Bao
PUBLISHED: 04-23-2013
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A new UPLC method was developed for the simultaneous determination of eleven characteristic flavonoid glycosides in Ginkgo biloba leaves. The natural occurrence of flavonoid glycosides in Ginkgo biloba leaves within one vegetative season was investigated for the first time. The analysis was performed on an Agilent ZORBAX Eclipse Plus C18 column (50 mm x 4.6 mm, 1.8 microm), the mobile phase A was acetonitrile, the mobile phase B was 0.4% phosphate aqueous solution in a gradient elution at a flow rate of 0.6 mL x min(-1), the detection was carried out at 360 nm. The result showed that eleven flavonoid glycosides had good linearity with good average recovery, separately. The method was proved to be accurate, rapid and good reproducible for the quality evaluation of Ginkgo biloba leaves, and provide an easy and rapid means for the quantitative analysis of flavonoid glycosides and their content fluctuation with seasons.
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[Application of simplified intensity modulated radiation therapy in gastric cancer after operation].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 03-29-2013
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To elucidate the application and the dosimetry characteristic of the simplified intensity modulated radiation therapy(sIMRT) for gastric cancer after operation, and to compare the dose distribution with intensity modulated radiation therapy(IMRT) and three-dimension conformal radiation therapy(3D-CRT).
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A colormetric and fluorescent chemosensor for adenosine-5-triphosphate based on rhodamine derivative.
Anal. Chim. Acta
PUBLISHED: 03-22-2013
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A rhodamine spirolactam derivative (1) was developed as a colormetric and fluorescent chemosensor for adenosine-5-triphosphate (ATP) via hydrogen bonds interaction. As far as we know, this is the first case to explore ATP-induced ring-opening of spirolactam in rhodamine derivatives. It exhibited a highly sensitive "turn-on" fluorescent response toward ATP with a 47-fold fluorescence intensity enhancement under 20 equiv. of ATP added. The chemosensor can be applied to the quantification of ATP with a linear range covering from 1.0×10(-7) to 2.0×10(-4) M and a detection limit of 2.5×10(-8) M. The experiment results show that the response behavior of 1 toward ATP is pH independent in medium condition (pH 6.0-8.0). Most importantly, the novel chemosensor has well solved the problem of serious interferences from other nucleoside polyphosphates such as ADP and AMP generally met by previously reported typical fluorescent chemosensors for ATP. Moreover, the response of the chemosensor toward ATP is fast (response time less than 3 min). In addition, the chemosensor can be used for the fluorescence assay for protein kinase activity with satisfactory results. The chemosensor for ATP based on hydrogen bonds interaction provided a novel strategy for the design of colormetric and ratiometric fluorescent probes for other target anions with high sensitivity and selectivity.
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Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-18-2013
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Suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, catalyzes histone 3 lysine 9 trimethylation and is involved in heterochromatin organization and genome stability. However, the mechanism for regulation of the enzymatic activity of SUV39H1 in cancer cells is not yet well known. In this study, we identified SET domain-containing protein 7 (SET7/9), a protein methyltransferase, as a unique regulator of SUV39H1 activity. In response to treatment with adriamycin, a DNA damage inducer, SET7/9 interacted with SUV39H1 in vivo, and a GST pull-down assay confirmed that the chromodomain-containing region of SUV39H1 bound to SET7/9. Western blot using antibodies specific for antimethylated SUV39H1 and mass spectrometry demonstrated that SUV39H1 was specifically methylated at lysines 105 and 123 by SET7/9. Although the half-life and localization of methylated SUV39H1 were not noticeably changed, the methyltransferase activity of SUV39H1 was dramatically down-regulated when SUV39H1 was methylated by SET7/9. Consequently, H3K9 trimethylation in the heterochromatin decreased significantly, which, in turn, led to a significant increase in the expression of satellite 2 (Sat2) and ?-satellite (?-Sat), indicators of heterochromatin relaxation. Furthermore, a micrococcal nuclease sensitivity assay and an immunofluorescence assay demonstrated that methylation of SUV39H1 facilitated genome instability and ultimately inhibited cell proliferation. Together, our data reveal a unique interplay between SET7/9 and SUV39H1--two histone methyltransferases--that results in heterochromatin relaxation and genome instability in response to DNA damage in cancer cells.
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Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.
Pest Manag. Sci.
PUBLISHED: 02-21-2013
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In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramats bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures.
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The axis of MAPK1/3-XBP1u-FOXO1 controls autophagic dynamics in cancer cells.
Autophagy
PUBLISHED: 02-20-2013
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Earlier studies have shown that macroautophagy is not a constitutively activated process, however, the mechanism of activation is not fully understood. Here, we report that autophagy is a dynamic process in cancer cells in response to glucose starvation. In addition, we determined that FOXO1 turnover is involved in the regulation of this dynamic process. X-box binding protein 1u (XBP1u) plays a critical role in FOXO1 degradation by recruiting FOXO1 to the 20S proteasome. Moreover, the phosphorylation of XBP1u by mitogen-activated protein kinases 1 and 3 (MAPK1/3, also known as ERK2/1) on serine residues 61 and 176 was found to be essential for the enhancement of the interaction between XBP1u and FOXO1. Thus, our findings support the hypothesis that the turnover of FOXO1 induced by MAPK1/3 and XBP1u is a critical factor regulating the autophagic process.
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Salusin-? in paraventricular nucleus increases blood pressure and sympathetic outflow via vasopressin in hypertensive rats.
Cardiovasc. Res.
PUBLISHED: 02-11-2013
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Salusin-? is a bioactive peptide with peripheral hypotensive, mitogenic and pro-atherosclerotic effects. The present study was designed to determine the roles of salusin-? in the paraventricular nucleus (PVN) and its relationship with arginine vasopressin (AVP) in hypertension and sympathetic activation.
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Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release.
Kidney Int.
PUBLISHED: 01-30-2013
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Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro phosphate-induced calcification model of vascular smooth muscle cells (VSMCs) and in an in vivo model of chronic renal failure, autophagy was inhibited by the superoxide dismutase mimic MnTMPyP, superoxide dismutase-2 overexpression, and by knockdown of the sodium-dependent phosphate cotransporter Pit1. Although phosphate-induced VSMC apoptosis was reduced by an inhibitor of autophagy (3-methyladenine) and knockdown of autophagy protein 5, calcium deposition in VSMCs was increased during inhibition of autophagy, even with the apoptosis inhibitor Z-VAD-FMK. An inducer of autophagy, valproic acid, decreased calcification. Furthermore, 3-methyladenine significantly promoted phosphate-induced matrix vesicle release with increased alkaline phosphatase activity. Thus, autophagy may be an endogenous protective mechanism counteracting phosphate-induced vascular calcification by reducing matrix vesicle release. Therapeutic agents influencing the autophagic response may be of benefit to treat aging or disease-related vascular calcification and osteoporosis.
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Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells.
Cancer Lett.
PUBLISHED: 01-29-2013
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Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.
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Structure, bioactivity and implications for environmental remediation of complexes comprising the fungicide hexaconazole bound to copper.
Pest Manag. Sci.
PUBLISHED: 01-26-2013
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BACKGROUND: In agricultural areas excessive amounts of toxic heavy metals are a growing threat to the environment and human health. Measures should be taken to minimise the risk of adverse health effects. Hence, we investigated the possibilities of hexaconazole (a commercial fungicidal) as a dual-function ligand that has heavy metal ions chelating and fungicidal activities. RESULTS: Metal chelation and fungicidal activities were studied by UV, elemental analysis, IR, thermogravimetric study and biological assays. Results showed that hexaconazole had selective binding capability with Cu(2+) over other ions such as Zn(2+) , Cd(2+) , Mn(2+) , Fe(2+) and Co(2+) . Soil leaching experiments showed that soil type had a limited effect on heavy-metal adsorption by hexaconazole; with decreasing pH, a notable rise of leaching effect was observed, which reached 22%. In addition, this complex exhibit better fungicidal activity against Blumeria graminis than the same dose of hexaconazole. CONCLUSION: This study demonstrates that hexaconazole had notable capabilities to chelate heavy metals as well as excellent fungicidal activity as a metal chelator. Given the mutual influence between pesticides and heavy metals in adsorption-desorption processes, these phenomena must be taken into account if they are to be applied rationally. © 2013 Society of Chemical Industry.
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Risk factors for high-altitude headache upon acute high-altitude exposure at 3700 m in young Chinese men: a cohort study.
J Headache Pain
PUBLISHED: 01-23-2013
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This prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure.
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Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.
PLoS ONE
PUBLISHED: 01-22-2013
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Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2) mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII) on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1) receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS) scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.
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Anxiety correlates with somatic symptoms and sleep status at high altitudes.
Physiol. Behav.
PUBLISHED: 01-15-2013
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High altitude exposure results in many physical and psychological discomforts, with anxiety and sleep disturbances being the most common ones. This cross-sectional study was performed to explore the relationship between anxiety, somatic symptoms, and sleep status at high altitude. A sample of 426 young males between 18 and 24 years old ascended from low-level land to 3600 m, where they acclimated for 40 days, before ascending to 4400 m. Questionnaires including the Louise Lake Score (LLS, for diagnosis of acute mountain sickness [AMS]), the Self-rating Anxiety Scale (SAS), the Epworth Sleepiness Scale (ESS), and the Athens Insomnia Scale (AIS) were administered immediately before departure from 3600 m (40th day) and the day after arrival at 4400 m (20 days after the first data collection). Physiological parameters were also measured. We observed that 49 of 426 and 51 of 329 people were diagnosed with anxiety according to SAS at 3600 and 4400 m, respectively. Physical symptoms were more severe in subjects with anxiety, and the severity of anxiety was significantly positively correlated to the severity of insomnia and increased heart rate (HR). Overall, these data indicate that after 40 days acclimatization in 3600 m, anxious persons have more severe somatic symptoms. When ascending to higher altitudes, these individuals are more likely to develop AMS, show more severe symptoms, and are prone to insomnia and more serious daytime sleepiness. Insomnia and elevated HR are indicators of anxiety severity.
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Reconstruction of through-and-through cheek defects with folded free anterolateral thigh flaps.
J. Oral Maxillofac. Surg.
PUBLISHED: 01-05-2013
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The purpose of this study was to assess the clinical application and therapeutic efficacy of through-and-through cheek defects reconstructed with folded anterolateral thigh (ALT) flaps.
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Survival impact of cervical metastasis in squamous cell carcinoma of hard palate.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 01-04-2013
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Evaluate the impact of cervical metastasis on the survival of patients with squamous cell carcinoma (SCC) of the hard palate.
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A randomized controlled study of single-agent cisplatin and radiotherapy versus docetaxel/cisplatin and radiotherapy in high-risk early-stage cervical cancer after radical surgery.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-03-2013
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This study explored whether docetaxel/cisplatin and radiotherapy (TP-R) increases overall survival (OS) and recurrence-free survival (RFS) compared to single-agent cisplatin and radiotherapy (C-R) in patients with high-risk early-stage cervical cancer post surgery.
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Superoxide anions in paraventricular nucleus modulate adipose afferent reflex and sympathetic activity in rats.
PLoS ONE
PUBLISHED: 01-01-2013
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Adipose afferent reflex (AAR) is a sympatho-excitatory reflex induced by chemical stimulation of white adipose tissue (WAT). Ionotropic glutamate receptors including NMDA receptors (NMDAR) and non-NMDA receptors (non-NMDAR) in paraventricular nucleus (PVN) mediate the AAR. Enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate the role and mechanism of superoxide anions in PVN in modulating the AAR.
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The Regulation of the Autophagic Network and Its Implications for Human Disease.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2013
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Autophagy has attracted a lot of attention in recent years. More and more proteins and signaling pathways have been discovered that somehow feed into the autophagy regulatory pathways. Regulation of autophagy is complex and condition-specific, and in several diseases, autophagic fluxes are changed. Here, we review the most well-established concepts in this field as well as the reported signaling pathways or components which steer the autophagy machinery. Furthermore, we will highlight how autophagic fluxes are changed in various diseases either as cause for or as response to deal with an altered cellular homeostasis and how modulation of autophagy might be used as potential therapy for such diseases.
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Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat.
PLoS ONE
PUBLISHED: 01-01-2013
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Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats.
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XBP-1u suppresses autophagy by promoting the degradation of FoxO1 in cancer cells.
Cell Res.
PUBLISHED: 01-01-2013
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Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation. However, autophagy is not persistently activated, which is poorly understood at a mechanistic level. Here, we report that turnover of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation. X-box-binding protein-1u (XBP-1u) has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome. In addition, the phosphorylation of XBP-1u by extracellular regulated protein kinases1/2 (ERK1/2) on Ser61 and Ser176 was found to be critical for the increased interaction between XBP-1u and FoxO1 upon glutamine starvation. Furthermore, knockdown of XBP-1u caused the sustained level of FoxO1 and the persistent activation of autophagy, leading to a significant decrease in cell viability. Finally, the inverse correlation between XBP-1u and FoxO1 expression agrees well with the expression profiles observed in many human cancer tissues. Thus, our findings link the dynamic process of autophagy to XBP-1u-induced FoxO1 degradation.
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[Surveillance of schistosomiasis in Caohui Village, Yangxin County, 2005-2010].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 12-16-2011
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The surveillance of schistosomiasis in a national schistosomiasis surveillance site, Caohui Village, Yangxin County, 2005 - 2010 showed that the infection rates of residents and livestock decreased from 4.56% and 28.33% to 1.19% and 1.67%, respectively. However, the endemic situation was still of instability. Therefore, we should strengthen the comprehensive control measures including the control of infectious sources in the light of local conditions to control the schistosomiasis endemic situation.
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[Survey on malaria vectors in Jiangsu Province, 2005-2009].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 12-15-2011
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To understand the species, density and seasonal variation of malaria vectors in Jiangsu Province, so as to provide scientific evidence for malaria control.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.