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1.
Eur J Pediatr ; 181(12): 4011-4017, 2022 Dec.
Article En | MEDLINE | ID: mdl-36114833

During the coronavirus disease 2019 (COVID-19) epidemic, many reports have indicated that children shed the virus longer than adults in stool, and that most of the children had mild or even asymptomatic infections, which increased the potential risk for feces to be a source of contamination and may play an important role in the spread of the virus. In this review, we collected relevant literature to summarize the duration of fecal viral shedding in children with COVID-19. We found that in about 60% of the cases, the fecal shedding time was between 28 and 42 days, which was much longer than that of adults. We further explored the possible reason for prolonged shedding and its the potential impact. The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the significant difference in expression of angiotensin-converting enzyme 2 (ACE2) in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children.   Conclusion: Children with COVID-19 show prolonged fecal shedding compared to adults. Several mechanisms may be involved in the longer fecal viral shedding. Viral shedding in the stool could be contributing to a possible route of transmission. Therefore, we think that further preventive measures in children should be taken to reduce the spread of the disease. What is Known: • Children with COVID-19 are more likely to have asymptomatic infections and to experience mild symptoms. • Some patients continue to shed the virus in feces, despite respiratory samples testing negative. What is New: • Children with COVID-19 carried a longer-term fecal viral shedding than adults. • The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the difference in expression of ACE2 in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children.


COVID-19 , Child , Adult , Humans , Virus Shedding , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , Asymptomatic Infections , RNA, Viral , Feces
2.
Neuropharmacology ; 178: 108230, 2020 11 01.
Article En | MEDLINE | ID: mdl-32693005

Anxiety disorders are the most prevalent group of mental disorders globally, leading to considerable losses in health, functioning and increase of medical costs. Till now, the search for novel pharmacological treatments is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. In central nervous system, the mitochondrially located translocator protein (18 kDa, TSPO) serves as the rate-limiting step for neurosteroidogenesis and influences GABAergic transmission. Since 5-HT is one of the most comprehensively studied neurotransmitter systems in the anxiety field, in the present study, we want to investigate whether 5-HT system is involved in the anxiolytic-like effects of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. Our data showed that YL-IPA08 could potentiate the 5-HTP-induced head-twitch response, and the anxiolytic-like effect of YL-IPA08 was abolished by pCPA or 5,7-DHT pretreatment in mice. Furthermore, we found that YL-IPA08 increased the extracellular levels of 5-HT in the rat ventral hippocampus in freely moving rat using the rapid and validated HPLC coupled with microdialysis. In addition, 5-HT level was positively correlated with the level of allopregnanolone. The above results suggest that 5-HT neurotransmission may play a critical role in the anxiolytic-like effects of YL-IPA08.


Anxiety/metabolism , Drug Delivery Systems/methods , Imidazoles/administration & dosage , Imidazoles/metabolism , Pyridines/administration & dosage , Pyridines/metabolism , Receptors, GABA/metabolism , Serotonin/metabolism , Synaptic Transmission/physiology , Animals , Anxiety/drug therapy , Anxiety/psychology , Hippocampus/drug effects , Hippocampus/metabolism , Ligands , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Microdialysis/methods , Rats , Rats, Sprague-Dawley , Synaptic Transmission/drug effects
3.
Metab Brain Dis ; 34(5): 1375-1384, 2019 10.
Article En | MEDLINE | ID: mdl-31236807

Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.


Antidepressive Agents/therapeutic use , Behavior, Animal/drug effects , Depression/drug therapy , Eating/drug effects , Piperidines/therapeutic use , Pyridones/therapeutic use , Animals , Antidepressive Agents/pharmacology , Depression/metabolism , Disease Models, Animal , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Male , Piperidines/pharmacology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Pyridones/pharmacology , Rats , Rats, Wistar , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Stress, Psychological/metabolism , Time Factors
4.
J Cell Mol Med ; 23(8): 5403-5414, 2019 08.
Article En | MEDLINE | ID: mdl-31148354

Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri-implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1-specific antisense morpholigos (Cyp26a1-MO) knockdown mice model and pCR3.1-Cyp26a1 vaccine mice model, we found that the number of uterine CD45+ CD11c+ MHCIIlo-hi F4/80- dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86hi ) was obviously lower and the percentage of immature DCs (CD86lo ) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow-derived DCs under Cyp26a1-MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.


Dendritic Cells/metabolism , Retinoic Acid 4-Hydroxylase/metabolism , Uterus/metabolism , Animals , Biomarkers/metabolism , CD11c Antigen/metabolism , Cell Differentiation/physiology , Embryo Implantation/physiology , Female , Male , Mice , Mice, Inbred BALB C , Pregnancy
5.
Bioorg Chem ; 81: 681-688, 2018 12.
Article En | MEDLINE | ID: mdl-30265992

A new series of nonquaternary conjugates for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. It was found that substituted salicylaldehydes conjugated to aminobenzamide through piperidine would produce efficient reactivators for sarin, VX and tabun inhibited hAChE, such as L6M1R3, L6M1R5 to L6M1R7, L4M1R3 and L4M1R5 to L4M1R7. The in vitro reactivation experiment for pesticides inhibited hAChE of these new synthesized oximes were conducted for the first time. Despite they were less efficient than obidoxime, some of them were highlighted as equal or more efficient reactivators in comparison to 2-PAM. It was found that introduction of peripheral site ligands could increase oximes' binding affinity for inhibited hAChE in most cases, which resulted in greater reactivation ability.


Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/toxicity , Drug Design , Enzyme Activators/chemistry , Enzyme Activators/pharmacology , Nerve Agents/toxicity , Pesticides/toxicity , Enzyme Activators/chemical synthesis , Humans , Molecular Docking Simulation , Sarin/toxicity
6.
Bioorg Med Chem ; 25(16): 4497-4505, 2017 08 15.
Article En | MEDLINE | ID: mdl-28684009

A new family of nonquaternary reactivators for nerve agent-inhibited human acetylcholinesterase (hAChE) were designed, synthesized and tested in this paper. It was found that salicylaldoximes were able to quickly cleave the P-S bond of organophosphate and avoid the reinhibition phenomenon in the reactivation process, but they lacked reactivating ability due to poor affinity for AChE. Based on a dual site binding strategy, different peripheral site ligands of AChE were introduced to achieve extra affinity. The in vitro reactivation experiments demonstrated that some of the yielding conjugates exhibited similar or even superior ability to reactivate sarin-, VX- or tabun-inhibited hAChE in comparison with the mono- and bis-pyridinium aldoximes currently used. Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators.


Acetylcholinesterase/metabolism , Cholinesterase Reactivators/pharmacology , Oximes/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Reactivators/chemical synthesis , Cholinesterase Reactivators/chemistry , Dose-Response Relationship, Drug , Humans , Ligands , Molecular Structure , Oximes/chemical synthesis , Oximes/chemistry , Structure-Activity Relationship
7.
Neuropharmacology ; 113(Pt A): 567-575, 2017 02.
Article En | MEDLINE | ID: mdl-27845056

The present study aimed to examine the molecular and cellular mechanisms underlying the antidepressant-like effect of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. We firstly used the chronic unpredictable stress (CUS) procedure of rats, a well validated stress-related animal model of depression, to further determine the antidepressant-like of YL-IPA08. And we found that YL-IPA08 caused significant suppression of inhibiting of locomotor activity, reducing the sucrose preference and increasing the latency to eat induced by CUS. In addition, YL-IPA08 treatment increased the levels of progesterone and allopregnanolone in the hippocampus and prefrontal cortex of post- CUS rats. Furthermore, long-term YL-IPA08 administration reversed dendritic shrinkage, down-regulation of neurotrophic signaling pathway within the hippocampus, as well as HPA dysfunctions simultaneously observed in the CUS rats. Collectively, the evidence presented above supports the notion that binding to TSPO and the subsequent synthesis of neurosteroid, maintenance of hippocampal morphologic and functional plasticity, and preventing HPA axis dysfunction, may account for the profound molecular and cellular mechanism underlying the antidepressant-like effect of YL-IPA08.


Antidepressive Agents/metabolism , Depression/metabolism , Imidazoles/metabolism , Imidazoles/therapeutic use , Pyridines/metabolism , Pyridines/therapeutic use , Receptors, GABA/metabolism , Stress, Psychological/metabolism , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Chronic Disease , Depression/drug therapy , Dose-Response Relationship, Drug , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Imidazoles/pharmacology , Male , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/metabolism , Pyridines/pharmacology , Rats , Rats, Wistar , Stress, Psychological/drug therapy , Treatment Outcome
8.
Br J Pharmacol ; 174(9): 769-780, 2017 05.
Article En | MEDLINE | ID: mdl-27882537

BACKGROUND AND PURPOSE: Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT1A receptor agonist properties, exerts a significant antidepressant effect in various animal models. The aim of present research was to further investigate the pharmacology of YL-0919. EXPERIMENTAL APPROACH: We first investigated the target profile of YL-0919 using [35 S]-GTPγS binding and microdialysis. To determine whether the 5-HT or noradrenergic systems are involved in the antidepressant-like effect of YL-0919, the 5-hydroxytryptophan (5-HTP)-induced head-twitch test and antagonism with a high dose of apomorphine were performed. Using the learned helplessness paradigm, the novelty suppressed feeding test, the Vogel-type conflict and elevated plus-maze test, we further verified the antidepressant-like and anxiolytic-like effects of YL-0919. The effects of YL-0919 on hippocampal long-term potentiation (LTP) and sexual behaviour were also evaluated. KEY RESULTS: Data from the present study demonstrated that YL-0919 displays partial 5-HT1A receptor agonist properties, producing a greater impact on extracellular 5-HT levels than a conventional SSRI (fluoxetine), as well as significant antidepressant and anxiolytic effects. Furthermore, YL-0919 treatment rapidly influenced the synaptic plasticity (enhancing LTP) of rats. Finally, at doses close to those producing antidepressant-like effects, YL-0919 did not result in a marked inhibition of sexual function. CONCLUSIONS AND IMPLICATIONS: These data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects.


Antidepressive Agents/metabolism , Drug Partial Agonism , Piperidines/metabolism , Pyridones/metabolism , Receptor, Serotonin, 5-HT1A/metabolism , Selective Serotonin Reuptake Inhibitors/metabolism , Serotonin 5-HT1 Receptor Agonists/metabolism , Animals , Anti-Anxiety Agents/metabolism , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Avoidance Learning/drug effects , Avoidance Learning/physiology , Dose-Response Relationship, Drug , Female , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Mice, Inbred ICR , Microdialysis/methods , Piperidines/pharmacology , Pyridones/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Serotonin 5-HT1 Receptor Agonists/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Sexual Behavior, Animal/drug effects , Sexual Behavior, Animal/physiology
9.
J Asthma ; 54(4): 335-340, 2017 May.
Article En | MEDLINE | ID: mdl-27715343

OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/ß-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/ß-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. METHODS: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3ß and ß-catenin was detected by Western Blot. RESULTS: Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/ß-catenin signaling pathway in DCs and asthmatic mouse lungs. CONCLUSIONS: Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/ß-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.


Anti-Inflammatory Agents/pharmacology , Asthma/drug therapy , Curcumin/pharmacology , Pneumonia/drug therapy , Wnt Proteins/drug effects , beta Catenin/drug effects , Animals , Asthma/immunology , B7-2 Antigen/biosynthesis , Biomarkers , Bronchoalveolar Lavage Fluid/cytology , CD11c Antigen/biosynthesis , CD40 Antigens/biosynthesis , Cytokines/drug effects , Dendritic Cells/drug effects , Dexamethasone/pharmacology , Disease Models, Animal , Eosinophils/drug effects , Female , Inflammation Mediators/metabolism , Mice , Mice, Inbred C57BL , Pneumonia/immunology , Signal Transduction , Wnt Proteins/immunology , beta Catenin/metabolism
10.
Toxicol Lett ; 246: 1-6, 2016 Mar 30.
Article En | MEDLINE | ID: mdl-26809136

Soman is a highly toxic nerve agent with strong inhibition of acetylcholinesterase (AChE), but of the few reactivators showing antidotal efficiency for soman-inhibited AChE presently are all permanently charged cationic oximes with poor penetration of the blood-brain barrier. To overcome this problem, uncharged reactivators have been designed and synthesized, but few of them were efficient for treating soman poisoning. Herein, we used a dual site biding strategy to develop more efficient uncharged reactivators. The ortho-hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. The in vitro experiment demonstrated that some of the resulting conjugates have robust activity against soman-inhibited AChE, and oxime 8b was highlighted as the most efficient one. Although not good as HI-6 in vitro, these new compounds hold promise for development of more efficient centrally acting reactivators for soman poisoning due to their novel nonquaternary structures, which are predicted to be able to cross the blood-brain barrier.


Cholinesterase Inhibitors/poisoning , Cholinesterase Reactivators/pharmacology , Soman/poisoning , Blood-Brain Barrier , Cholinesterase Reactivators/chemical synthesis , Humans , Oximes/pharmacokinetics , Oximes/pharmacology , Pyridinium Compounds/pharmacokinetics , Pyridinium Compounds/pharmacology
11.
Sci Rep ; 5: 11332, 2015 Jul 10.
Article En | MEDLINE | ID: mdl-26161529

Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices.


Cyclic Nucleotide Phosphodiesterases, Type 4/genetics , Depression/etiology , Memory Disorders/etiology , Prefrontal Cortex/metabolism , Animals , Body Weight/drug effects , Corticosterone/blood , Cyclic AMP/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/chemistry , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Dendrites/drug effects , Dendrites/physiology , Depression/drug therapy , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Male , Maze Learning/drug effects , Memory Disorders/drug therapy , Mice , Mice, Inbred BALB C , Phosphodiesterase 4 Inhibitors/pharmacology , Phosphodiesterase 4 Inhibitors/therapeutic use , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rolipram/pharmacology , Rolipram/therapeutic use , Signal Transduction/drug effects , Stress, Physiological
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(3): 843-7, 2015 Jun.
Article Zh | MEDLINE | ID: mdl-26117047

OBJECTIVE: This study was aimed to explore the new mechanism of α-Galactosyleramide (α-GalCer), a synthetic glycolipid, and a well-known activator of natural killer T cells (NKT) for improving acute graft-versus-host disease(aGVHD). METHODS: Murine allogeneic bone marrow transplantation (allo-BMT) model was established. Recipient mice were injected intraperitoneally with α-GalCer immediately after allo-BMT, whereas mice from the vehicle groups received the diluent (DMSO) only. The severity degree of aGVHD was estimated by survival, aGVHD clinical score and pathology. The mechanism of aGVHD reduced by α-GalCer was explored by detecting T cells migration in vivo and in vitro. RESULTS: Mice in α-GalCer group survived longer than in control group, and their clinical and pathological status of aGVHD were lighter. α-GalCer reduced aGVHD by altering donors T cell migration. CONCLUSION: After allo-BMT α-GalCer reduces aGVHD by altering donor T cells migration.


Cell Movement , Graft vs Host Disease , Acute Disease , Animals , Bone Marrow Transplantation , Mice , Natural Killer T-Cells , Tissue Donors , Transplantation, Homologous
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 431-4, 2015 Apr.
Article Zh | MEDLINE | ID: mdl-25948199

OBJECTIVE: To explore the correlation between the level of serum 25-hydroxyvi-tamin D3 and the development and prognosis of NHL in order to provide the theoretical basic for the diagnosis, treatment and prognosis of NHL. METHODS: The serum 25-hydroxyvitamin D's level of 84 NHL patients and 60 healthy persons was detected by using enzyme-linked immunsorbent assay. RESULTS: The level of serum 25-hydroxyvitamin D3 in NHL group was significantly lower than that in normal control group and the difference between NHL patients and normal controls was statistically significant. The stage and cell source of NHL patients showed little effect on the level of 25-hydroxyvitamin D3. There were significant differences of the level of 25-hydroxyvitamin D3 in different group and sites of origin as well as in presence or absence of bone marrow infiltration. CONCLUSIONS: The level of 25-hydroxyvitamin D3 can be considered as tumor burden index of NHL and can be used to evaluate the prognosis of NHL.


Lymphoma, Non-Hodgkin , Calcifediol , Humans , Prognosis
14.
Int J Clin Exp Pathol ; 8(10): 13739-46, 2015.
Article En | MEDLINE | ID: mdl-26722602

Asthma is a complex inflammatory disease involving the critical actions of several important cytokines. Epidemiological data show that obesity could increase the risk of asthma, and insulin resistance, or metabolic syndrome are an important risk factor for obesity asthma. Some studies identified that upstream of the transcription start site within the TNF-α gene promoter region-308 polymorphism was associated insulin resistance or metabolic disorders, while this site was closely related to asthma. But no research was performed to evaluate the influence of TNF-α-308G/A polymorphism on metabolic syndrome in asthmatic patients. Here, we recruited 248 asthmatic patients, who were separated into asthma with Mets/asthma without Mets groups and 226 matched healthy controls from Hebei Province to evaluate the influence of TNF-α-308G/A polymorphism on metabolic syndrome in asthmatic patients. Single nucleotide polymorphism of TNF-α-308 locus was genotyped using PCR-RFLP. Some biochemical variables were also determined. Our result showed that the genotypic and allelic frequency of rs1800629 did not show significant difference between asthmatic patients and normal controls. However, the frequency of A allele was significantly higher in asthma group with Mets (22.36%) than in controls (15.71%) (P = 0.02; OR = 0.647; 95% CI = 0.447-0.936). After analyzing the relationship between biochemical features of patients and genotype of TNF-α-308G/A, we found levels of LDL cholesterol, TNF-α and insulin, and HOMA-IR were significantly higher in the asthmatic patients carrying the GA and AA genotypes than in the carriers of GG genotype of rs1800629 (P = 0.029, P = 0.022, P = 0.043, respectively). Thus, our data suggested that TNF-α-308G/A variation was related to metabolic phenotype in asthma patients. Furthermore, we first identified TNF-α-308 A allele was the risk factor for asthmatic patients with Mets in Hebei population, China.


Asthma/genetics , Metabolic Syndrome/genetics , Polymorphism, Single Nucleotide/genetics , Tumor Necrosis Factor-alpha/genetics , Adult , Alleles , Asthma/complications , China , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Insulin/metabolism , Male , Metabolic Syndrome/complications , Middle Aged , Obesity , Point Mutation , Risk Factors , Tumor Necrosis Factor-alpha/blood
15.
Bioorg Med Chem Lett ; 24(24): 5743-5748, 2014 Dec 15.
Article En | MEDLINE | ID: mdl-25453812

Herein, we described a new class of uncharged non-pyridinium reactivators for nerve agent-inhibited acetylcholinesterase (AChE). Based on a dual site binding strategy, we conjugated the imidazolium aldoxime to different peripheral site ligands (PSLs) of AChE through alkyl chains. Compared with the known quaternary pyridinium reactivators, two of the resulting conjugates (7g and 7h) were highlighted to be the first efficient non-pyridinium oxime conjugates exhibiting similar or superior ability to reactivate sarin-, VX- and tabun-inhibited AChE. Moreover, they were more broad-spectrum reactivators.


Acetylcholinesterase/metabolism , Chemical Warfare Agents/chemistry , Cholinesterase Reactivators/chemistry , Oximes/chemistry , Acetylcholinesterase/chemistry , Binding Sites , Cholinesterase Reactivators/chemical synthesis , Cholinesterase Reactivators/metabolism , Humans , Imidazoles/chemistry , Kinetics , Ligands , Molecular Docking Simulation , Oximes/chemical synthesis , Oximes/metabolism , Protein Binding , Protein Structure, Tertiary
16.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2233-8, 2014 Jun.
Article Zh | MEDLINE | ID: mdl-25244751

In order to establish the stable andreliable ISSR-PCR System of Lysimachia christinae, L16 (4(5)) orthogonal design, which based on 7 levels of single factor experiment, were used in this study. The variance analysis was carried out by SPSS 19.0, and 5 main factors affecting the reaction system were optimized in 4 levels. The best annealing temperature was selected by the optimized reaction system. And the stability and reliability of this system was tested by 23 samples from different origins. The results showed that the five factors (DNA template, primer, dNTP, Mg2+ and Taq enzyme) were the most impacts on the amplified results of ISSR-PCR of L. christinae. The order of the influence was: primer > Taq enzyme > DNA template > Mg2+ > dNTP. The optimal system, which was determined by multiple comparison on different levels of each factor, was total volume of 25 microL, including DNA template 60 ng, primer 0.3 micromol x L(-1), dNTP 0.2 mmol x L(-1), Mg2+ 1.8 mmol x L(-1), Taq enzyme 1.25 U. The optimal system was stable and reliable tested by 23 samples from different origins. This study lays the foundation for genetic diversity analysis, fine varieties selection and molecular identification of L. christinae, and provides reference for optimization on ISSR-PCR system of other speciesin future.


Microsatellite Repeats , Polymerase Chain Reaction/methods , Primulaceae/classification , Primulaceae/genetics , DNA Primers/genetics , DNA, Plant/genetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/classification , Quality Control
17.
Int J Neuropsychopharmacol ; 17(10): 1659-69, 2014 Oct.
Article En | MEDLINE | ID: mdl-24763106

Recently, the translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR) and both the starting point and an important rate-limiting step in neurosteroidogenesis, has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD) because it affects the production of neurosteroids, reinforcing the hypothesis that selective TSPO ligands could potentially be used as anti-PTSD drugs. As expected, we showed that chronic treatment with YL-IPA08 [N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl)-7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, caused significant suppression of enhanced anxiety and contextual fear induced in the inescapable electric foot-shock-induced mouse model of PTSD and the time-dependent sensitization (TDS) procedure. These effects were completely blocked by the TSPO antagonist PK11195. Furthermore, YL-IPA08 could increase the level of allopregnanolone in the prefrontal cortex and serum of post-TDS rats, and these effects were antagonized by PK11195. In summary, the findings from the current study showed that YL-IPA08, a potent and selective TSPO ligand, had a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.


Anti-Anxiety Agents/therapeutic use , Stress Disorders, Post-Traumatic/drug therapy , Analysis of Variance , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Electroshock/adverse effects , Freezing Reaction, Cataleptic/drug effects , Imidazoles/pharmacology , Imidazoles/therapeutic use , Isoquinolines/pharmacology , Isoquinolines/therapeutic use , Male , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Pyridines/pharmacology , Pyridines/therapeutic use , Rats , Rats, Sprague-Dawley , Receptors, GABA/metabolism , Sertraline/pharmacology , Sertraline/therapeutic use , Stress Disorders, Post-Traumatic/etiology
18.
Brain Res ; 1565: 37-47, 2014 May 27.
Article En | MEDLINE | ID: mdl-24735651

Madecassoside, a triterpenoid derivative isolated from Centella asiatica, exhibits anti-inflammatory and antioxidant activities. We investigated its neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24mg/kg, i.v.) was administered 1h after the start of reperfusion, and neurological deficit score and infarct volume were evaluated 24h later. Neuronal apoptosis was assessed by performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, and pathological brain damage was estimated by performing hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide dismutase activity, reduced glutathione levels, and nitric oxide levels were also determined. mRNA and protein expression of pro-inflammatory cytokines (Interleukin-1ß/6, and tumor necrosis factor-α) were measured by real-time RT-PCR and ELISA, respectively; NF-κB p65 expression was determined by western blotting. Madecassoside significantly reduced brain infarct area, resolved neurological deficit, and ameliorated neuronal apoptosis. It also significantly reduced the levels of malondialdehyde and nitric oxide, and augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover, the levels of pro-inflammatory cytokines and NF-κB p65 significantly reduced after madecassoside treatment. These results indicate that madecassoside is neuroprotective and may be useful in reducing the damage caused by stroke.


Brain Ischemia/drug therapy , Neuroprotective Agents/therapeutic use , Reperfusion Injury/drug therapy , Triterpenes/therapeutic use , Animals , Apoptosis/drug effects , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Male , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(6): 1409-12, 2013 Dec.
Article Zh | MEDLINE | ID: mdl-24370021

This study was aimed to summarize the clinical and pathological features of patients with acute leukemia combined with intracranial hemorrhage. The clinical and pathological data of 41 adult patients diagnosed as acute leukemia in our hospital from 1953 to 1990 year were analyzed retrospectively. The results showed that there were 35 cases of AML, 6 cases of ALL; 9 cases in clinical hematologic remission, 32 cases in non-remission, 3 cases of AL with hypertension, 2 cases of AL with diabetes, 4 cases of AL with sepsis, 19 cases with WBC ≥ 100×10(9)/L; the pathologic examination showed 4 cases of AL accompanied with disseminated intravascular coagulation, 10 cases with prothrombin time INR ≥ 1.5, 26 cases with multifocal intracranial hemorrhage, 7 cases with single intracranial hemorrhage, 8 cases with diffused spotting intracranial hemorrhage; the examination also showed that 84 hemorrhage foci were found in 41 cases of AL, among them 46 foci located under cerebral cortex, 23 foci in cerebellum, 6 in basal ganglia, 5 foci in pons, 2 foci in thalamus, 2 foci in spinal cord. It is concluded that the intracranial hemorrhage is a major cause resulting in death of AL patients which should be think highly, and the diagnosis and treatment should be conducted through comprehensive analysis.


Intracranial Hemorrhages/pathology , Leukemia/pathology , Acute Disease , Adolescent , Adult , Female , Humans , Intracranial Hemorrhages/complications , Leukemia/complications , Male , Middle Aged , Retrospective Studies , Young Adult
20.
Article En | MEDLINE | ID: mdl-23935686

Acupuncture as an oriental natural healing therapy with prolonged history has been extensively utilized in the management of great numbers of disorders. Deqi, a renowned acupuncture needling sensation, is profoundly regarded as the predictor and also the prerequisite of a preferable acupuncture treatment efficacy. Till now, there is still no consistency being reached towards the mechanism of acupuncture Deqi as a result of the discrepancy for publicly acknowledged evidence. Recent visualized research on Deqi using modern technologies has demonstrated possible central mechanism towards it. However, there is a conspicuous paradox underway in the research of cerebral response to acupuncture Deqi. This paper provided a view of up-to-date studies using visualized tools to characterize the brain response to acupuncture Deqi, such as functional magnetic resonance imaging (fMRI) and positron emission tomography/computed tomography (PET/CT). The paradox was extruded to highlight certain reasons from a TCM view. It is hypothesized that acupoints located at different dermal sites, state of participant, and needling manipulation can all contribute to the current paradox. Hence, further studies on acupuncture Deqi should pay more attention to the strategy of experiment design with generalized measurement, valid sham control methods, and more to subjects in diseased condition.

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