Dan Lv

Vascular Endothelial Growth Factor +936C/T and +405G/C Polymorphisms and Cancer Risk: a Meta-analysis

BACKGROUND AND AIMSnA number of investigators have studied the possible association between vascular endothelial growth factor (VEGF) polymorphisms and cancer risk, but the results have been conflicting. To examine the risk of cancer associated with the +936C/T and +405G/C polymorphisms of VEGF, all available studies were considered in the present meta-analysis.nnnMETHODSnWe performed a computerized search of PubMed and Embase database for relevant studies. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.nnnRESULTSnOverall, the 936C allele showed no significant effect on cancer risk compared with the 936T allele in all subjects (OR = 0.77, 95% CI = 0.53-1.14; random model). Similarly, no significant effect of 405G allele compared with 405C on cancer risk was found (OR = 1.08, 95% CI = 0.94-1.24; random model). It indicated that the VEGF +936C/T and +405G/C polymorphisms might not be risk factors for cancer, but the 936C allele was associated with a decreased risk of oral cancer (OR = 0.72, 95% CIxa0= 0.53-0.97; fixed model).nnnCONCLUSIONSnThe evidence from our meta-analysis supports that there was an association between 936C allele and decreased oral cancer risk, although no evidence of association between VEGF +936C/T or +405G/C polymorphism and cancer was observed in all examined patients. Further studies based on larger, stratified population are required to explore the role of VEGF polymorphisms on cancer risk.

Polymorphism of vascular endothelial growth factor -2578C/A with cancer risk: evidence from 11263 subjects

Published data on the association between vascular endothelial growth factor (VEGF) –2578C/A polymorphism and cancer risk is inconclusive. To derive a more precise estimation of association between VEGF –2578C/A polymorphism and the risk of cancer, we performed a meta-analysis of 5415 cancer cases and 5848 controls from 16 published case–control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Our meta-analysis indicated that VEGF –2578C/A polymorphism was associated with the risk of colorectal cancer under homozygote comparison (ORxa0=xa00.70, 95% CIxa0=xa00.53–0.92), dominant model (ORxa0=xa00.72, 95% CIxa0=xa00.57–0.92), and recessive model (ORxa0=xa00.82, 95% CIxa0=xa00.67–1.01), although no evidence of association between VEGF –2578C/A polymorphism and cancer risk was observed as we compared in the pooled analyses (homozygote comparison: ORxa0=xa00.97, 95% CIxa0=xa00.81–1.16). More studies are needed to detect VEGF –2578C/A polymorphism and its association with cancer in different ethnic populations incorporated with environmental exposures in the susceptibility of different kinds of cancer.

Macrolide therapy in cryptogenic organizing pneumonia: A case report and literature review

Cryptogenic organizing pneumonia (COP) is a pulmonary disorder associated with nonspecific clinical presentations. The macrolide class of antimicrobial agents is widely used to treat infectious and inflammatory respiratory diseases in humans. The present study reports a case of COP that was effectively treated with azithromycin in combination with glucocorticoid. A literature review of similar cases is also presented. It was found that all COP patients in the literature received macrolide treatment, including six cases with unknown clinical outcomes. For the remaining 29 patients, 20 patients initially received the macrolide as a single therapy and 4/5 of them (16 cases) were cured with a treatment time of 3–14 months, while 1/5 (4 cases) showed no improvement after treatment for 1 month and were switched to a glucocorticoid or combination treatment with a glucocorticoid, after which the disease was finally well-controlled. Side-effects of macrolide were rare. Based on this analysis, it is recommended that macrolides can be used as a first-line therapy in patients with mild COP. For patients with recurrent COP, it is suggested that macrolides should be used as an adjunctive therapy with other treatments, such as a glucocorticoid.

Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea: a HuGE review and meta-analysis

BackgroundSeveral epidemiological studies have been conducted to examine the association between leptin and leptin receptor (LEPR) gene polymorphisms and risk of obstructive sleep apnea (OSA). However, the results remain conflicting rather than conclusive.ObjectiveThe aim of this study was to investigate associations of leptin and LEPR polymorphisms and risk of OSA.MethodsWe carried out a search in MEDLINE, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95xa0% confidence intervals (CIs) were calculated to assess the strength of the association.ResultsOverall, no statistically significant association of OSA risk and polymorphisms of Gln233Arg, Lys109Arg, Lys656Asn, 19A/G, Pro1019Arg, and 2548G/A was found. However, in the stratified analysis by ethnicity, Gln233Arg polymorphism was associated with a significantly decreased risk of OSA in European (homozygote comparison: ORu2009=u20090.35, 95xa0% CIu2009=u20090.14–0.85, Pu2009=u20090.02), but not for Asian population.ConclusionsOur study suggested that leptin and LEPR polymorphisms had no association with OSA risk in all examined patients, whereas there was an association between Gln233Arg polymorphism and OSA risk in Europeans.

Vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release and membrane GluA1 activation is involved in the rapid antidepressant-like effects of scopolamine in mice

ABSTRACT Emerging data have identified certain drugs such as scopolamine as rapidly acting antidepressants for major depressive disorder (MDD) that increase glutamate release and induce neurotrophic factors through &agr;‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) activation in rodent models. However, little research has addressed the direct mechanisms of scopolamine on AMPAR activation or vesicular glutamate transporter 1 (VGLUT1)‐mediated glutamate release in the prefrontal cortex (PFC) of mice. Herein, using a chronic unpredictable stress (CUS) paradigm, acute treatment with scopolamine rapidly reversed stress‐induced depression‐like behaviors in mice. Our results showed that CUS‐induced depression‐like behaviors, accompanied by a decrease in membrane AMPAR subunit 1 (GluA1), phosphorylated GluA1 Ser845 (pGluA1 Ser845), brain‐derived neurotrophic factor (BDNF) and VGF (non‐acronymic) and an increase in bicaudal C homolog 1 gene (BICC1) in the PFC of mice, and these biochemical and behavioral abnormalities were ameliorated by acute scopolamine treatments. However, pharmacological block of AMPAR by NBQX infusion into the PFC significantly abolished these effects of scopolamine. In addition, knock down of VGLUT1 by lentiviral‐mediated RNA interference in the PFC of mice was sufficient to induce depression‐like phenotype, to decrease extracellular glutamate accumulation and to cause similar molecular changes with CUS in mice. Remarkably, VGLUT1 knockdown alleviated the rapid antidepressant‐like actions of scopolamine and the effects of scopolamine on membrane GluA1‐mediated BDNF, VGF and BICC1 changes. Altogether, our findings suggest that VGLUT1‐mediated glutamate release and membrane GluA1 activation may play a critical role in the rapid‐acting antidepressant‐like effects of scopolamine in mice. HighlightsAcute treatment with scopolamine prevents depression‐like behaviors in mice.Membrane GluA1‐mediated down‐stream molecular changes involve in these effects.Knock‐down of VGLUT1 in the PFC attenuates scopolamines effects on behaviors of mice.

The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice

Abstract Background Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-type voltage-dependent calcium channels in the action of scopolamine. Methods Herein, we investigated the mechanisms underlying behavioral responses to various doses of scopolamine in mice to clarify the involvement of L-type voltage-dependent calcium channels in its modes of action. Open field test, novel object recognition test, and forced swimming test were performed on mice administered varied doses of scopolamine (0.025, 0.05, 0.1, 1, and 3 mg/kg, i.p.) alone or combined with L-type voltage-dependent calcium channel blocker verapamil (5 mg/kg, i.p.). Then, the changes in brain-derived neurotrophic factor and neuropeptide VGF (nonacronymic) levels in the hippocampus and prefrontal cortex of these mice were analyzed. Results Low doses of scopolamine (0.025 and 0.05 mg/kg) produced significant antidepressant-like effects in the forced swimming test, while higher doses (1 and 3 mg/kg) resulted in significant memory deficits and depressive-like behaviors. Moreover, the behavioral changes in responses to various doses may be related to the upregulation (0.025 and 0.05 mg/kg) and downregulation (1 and 3 mg/kg) of brain-derived neurotrophic factor and VGF in the hippocampus and prefrontal cortex in mice. We further found that the rapid-acting antidepressant-like effects and the upregulation on brain-derived neurotrophic factor and VGF produced by a low dose of scopolamine (0.025 mg/kg) were completely blocked by verapamil. Conclusions These results indicate that L-type voltage-dependent calcium channels are likely involved in the behavioral changes in response to various doses of scopolamine through the regulation of brain-derived neurotrophic factor and VGF levels.

Correction to: Dabigatran-Induced Massive Spontaneous Hemothorax

Page 3, Tablexa02, ‘Renal function indexes at different dates after admission’: The cell entry in column 2, detailing the patient’s urea concentration (μmol/L) on Day 1,

Mechanisms underlying the rapid-acting antidepressant-like effects of neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62

ABSTRACT Previous studies have revealed that neuropeptide VGF (non‐acronymic) C‐terminal peptide TLQP‐62 rapidly activates brain‐derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/&agr;‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor/mammalian target of rapamycin (mTOR) signaling and produces antidepressant‐like actions in rodents. In addition, acute TLQP‐62 infusion also markedly changes the AMPA receptor GluA1 subunit phosphorylation at Ser 845 (pGluA1 Ser845) in the PFC of mice, indicating that the GluA1 may contributes to the rapid antidepressant‐like effects of TLQP‐62. However, how to regulate the TrkB‐mediated signaling and GluA1 changes in the prefrontal cortex (PFC) by TLQP‐62 remains unclear. Herein, acute administration of TLQP‐62 into PFC produced rapid‐acting antidepressant‐like effects in mice. Additionally, we confirmed that TLQP‐62 ameliorated the depression‐like behaviors induced by chronic social defeat stress (CSDS) in mice. Further investigation demonstrated that this effect of TLQP‐62 was mediated by activation of TrkB and mTOR, which proceeded to decrease bicaudal C homolog 1 gene (BICC1) and increase synaptic protein expression, including GluA1 subunit and pGluA1 Ser845. Notably, we further found that beneficial effects of TLQP‐62 on depression‐like behaviors and TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC of mice were significantly abolished by TrkB antagonist ANA‐12. In conclusion, our findings indicate that TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC may involve in the rapid‐acting antidepressant‐like actions of TLQP‐62 in mice. HIGHLIGHTSAcute administration of TLQP‐62 into PFC produced rapid‐acting antidepressant‐like effects in mice.Microinfusion of TLQP‐62 in to PFC of mice ameliorates the depression‐like behaviors.TLQP‐62 alleviates depression‐like behaviors may via regulating TrkB/mTOR/BICC1 signaling and GluA1 phosphorylation.

GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13.

Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluA1 in the rapid antidepressant-like actions of ketamine in mice

Previous studies have suggested that rapid reductions in depression-like behaviors are observed in response to sub-anesthetic-doses of ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist. Neuropeptide VGF (non-acronymic) is a critical effector of depression-like behaviors and is thought to be involved in the antidepressant actions of ketamine that have been demonstrated. However, the mechanism underlying the involvement of VGF in the anti-depressant action of ketamine remains unclear. We found that single dose ketamine treatment reversed CSDS-induced depression-like behaviors and decrease of VGF in the PFC of mice. To investigate the involvement of VGF in the antidepressant-like effects of ketamine, a lentivirus vector for VGF was constructed to knockdown the expression of VGF in the prefrontal cortex (PFC) of mice. The biochemical and behavioral effects of this VGF knockdown were examined, using the open field, forced swim, and sucrose preference tests. Our results show that knockdown of VGF increased the immobility time and decreased the sucrose preference in mice. These effects were not improved by ketamine administration. In addition, we found that knockdown of VGF significantly decreased the expression of phosphorylation of tropomyosin receptor kinase B (TrkB), mammalian target of rapamycin (mTOR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 Ser845 and increased the expression of bicaudal C homolog 1 (BICC1) in the mouse PFC, and blocked the regulation of TrkB/mTOR/BICC1 signaling and GluA1 phosphorylation by ketamine. Our results indicate that the rapid onset antidepressant-like actions of ketamine require VGF to regulate TrkB/mTOR/BICC1 signaling and AMPA receptor GluA1 phosphorylation.