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1.
Rev Cardiovasc Med ; 24(1): 31, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39076862

RESUMEN

Background: To assess the effectiveness of the nurse-led individualised self-care model on myocardial infarction (MI) patients with diabetes. Methods: A total of 120 MI patients were enrolled from May 2020 to December 2021. The intervention group received the nurse-led individualised self-care model (n = 60), whereas the control group only received routine health education (n = 60). The Myocardial Infarction Dimensional Assessment Scale (MIDAS), Coronary Heart Disease Self-Management Behavior Scale (CSMS), Self-Rated Abilities for Health Practices (SRAHP) scale, General Self-Efficacy Scale (GSES), Hospital Anxiety and Depression Scale (HADS), blood glucose and nursing satisfaction in both groups were observed and recorded. Results: The six MIDAS subscales except for insecurity, and all dimensions of the CSMS, SRAHP, GSES and HADS scores, of the intervention group were significantly improved compared to those of the control group (p < 0.05). Compared with the control group (5.69 ± 1.43 mmol/L), the intervention group showed a decrease in the serum levels of fasting blood glucose (4.83 ± 1.57 mmol/L; p < 0.01). Conclusions: Our pilot study provides preliminary evidence supporting the feasibility of implementing nurse-led individualised self-care, suggesting its preliminary effects in improving health-related quality of life, self-care ability, health behaviours, self-efficacy, social support and nursing satisfaction among MI patients with diabetes. However, considering the unblinded and pilot nature of this study, these positive results should be interpreted with caution. Clinical Trial Registration: OSF Registration number: DOI 10.17605/OSF.IO/DVW95 (https://archive.org/details/osf-registrations-dvw95-v1).

2.
Zhongguo Zhong Yao Za Zhi ; 44(1): 82-87, 2019 Jan.
Artículo en Zh | MEDLINE | ID: mdl-30868816

RESUMEN

To achieve a comprehensive understanding of heavy metals and harmful elements residues in Niuhuang Qingwei Pills,49 samples from 18 manufactures were collected from 31 provinces in China.Risk assessment and control preparations were applied innovatively in evaluation of exogenous pollution in traditional Chinese Medicine.Determination methods for Pb,Cd,As,Hg and Cu were established by inductively coupled plasma mass spectrometry(ICP-MS).Based on the procedures including hazard identification,hazard characterization,exposure assessment and risk characterization,risk assessment was performed and residual limits for Pb,Cd,As,Hg and Cu in the drug were formulated.The results showed that the hazardous quotients(HQ) of the elements were decreased in the following order:Pb>As>Cu>Hg>Cd,and the total hazardous index(HI) of heavy metals and harmful elements in Niuhuang Qingwei Pills was above 1,implying health risk of the drug.Under the proposed limits,5 elements in the control preparation as well as Cd and Cu in the samples were within the limits range,but the excess rates of Pb,As and Hg in the samples were 12%,12% and 14%,respectively.For the first time,basic steps for risk assessment of Chinese patent medicine were established,which provided model and reference for risk assessment and limit formulation of other drugs.


Asunto(s)
Contaminación de Medicamentos , Medicamentos Herbarios Chinos/análisis , Metales Pesados/análisis , China , Medicamentos Herbarios Chinos/normas , Medición de Riesgo
3.
J Cell Physiol ; 233(4): 3207-3217, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28834540

RESUMEN

AMAP1 was a GTPase-activating protein that regulates cytoskeletal structures in focal adhesions, circular dorsal ruffles, and promote cell differentiation in tumor cells. But the activation and function of AMAP1 in breast cancer remain largely unexplored. Here we show that AMAP1 was phosphorylated and translocated to plasma membrane and formed a stable complex with Pyk2 in response to CCL18. Moreover, CCL18-dependent AMAP1 translocation interfered the AMAP1-IKK-ß interaction, resulting in nuclear factor-kappaB (NF-κB) activation. Depletion of AMAP1 expression by RNAi efficiently reversed the CCL18-induced epithelial to mesenchymal transition (EMT) of breast cancer cells and as well as CCL18-induced adhesion, migration and invasion. Strikingly, AMAP1 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognosis in breast cancers. Given that AMAP1 mediated CCL18-induce activation of NF-κB and promoted breast cancer metastasis, AMAP1 may represent a therapeutic target for the eradication of breast cancer metastasis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Quimiocinas CC/metabolismo , Transición Epitelial-Mesenquimal , Adulto , Anciano , Adhesión Celular , Membrana Celular/metabolismo , Movimiento Celular , Femenino , Quinasa 2 de Adhesión Focal/metabolismo , Humanos , Quinasa I-kappa B/metabolismo , Células MCF-7 , Persona de Mediana Edad , Modelos Biológicos , FN-kappa B/metabolismo , Invasividad Neoplásica , Fosforilación , Unión Proteica , Transporte de Proteínas
4.
Appl Microbiol Biotechnol ; 102(16): 7113-7121, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29876603

RESUMEN

Metabolomics has been a potential tool for strain improvement through analyzing metabolite changes in the context of different conditions. However, the availability of a universal metabolite profiling analysis is still a big challenge. In this study, we presented an optimized liquid chromatography-tandem mass spectrometry-based metabolomics methodology for Corynebacterium glutamicum, an important industrial workhorse. It was found that quenching the cellular metabolism with 5-fold volume of - 20 °C 40% methanol was highly recommended due to its lower cell damage rate and higher intracellular metabolite recovery rate. For extracting intracellular metabolites, ethanol/water (3:1, v/v) at 100 °C combined with acidic acetonitrile/water (1:1, v/v, with 0.1% formic acid) at - 20 °C achieved the unbiased metabolite profiling of C. glutamicum. The established methodology was then applied to investigate the intracellular metabolite differences between C. glutamicum ATCC 13032 and an mscCG-deleted mutant under biotin limitation condition. It was observed that in the presence of the functional L-glutamate exporter MscCG, biotin limitation led to accumulation of intracellular 2-oxoglutarate but not L-glutamate. Deletion of mscCG severely inhibited L-glutamate excretion and resulted in a dramatical increase of intracellular L-glutamate, which in turn affected the metabolite profile. The optimized metabolomics methodology holds promise for promoting studies on metabolic mechanism of C. glutamicum.


Asunto(s)
Proteínas Bacterianas/metabolismo , Corynebacterium glutamicum/metabolismo , Metabolómica/métodos , Transporte Biológico , Biotina/metabolismo , Corynebacterium glutamicum/genética , Ácido Glutámico/metabolismo , Mutación , Espectrometría de Masas en Tándem/métodos
5.
Zhongguo Zhong Yao Za Zhi ; 43(18): 3662-3667, 2018 Sep.
Artículo en Zh | MEDLINE | ID: mdl-30384530

RESUMEN

Astragalus membranaceus pathogenesis-related protein 10 (AmPR-10) is largely expressed in case of environmental pressure and pathogen invasion. This study aims to explore the biochemical functions of AmPR-10. The dried root of Astragalus membranaceus was mechanically homogenized and extracted by Tris-HCl buffer to obtain its crude extract, which was then purified by anion exchange chromatography and gel filtration chromatography to obtain electrophoretically pure AmPR-10. The nuclease activity of AmPR-10 was tested with different RNAs by detecting the absorption value at 260 nm. The results demonstrated potent nuclease activity toward yeast tRNA, yeast RNA, Poly (A) and Poly (C). The optimum reaction temperature was 50 °C and pH was 7-8. EDTA showed no effect on its activity, while Mg²âº exhibited potent activation effect on the activity, and Co²âº, Ca²âº and Zn²âº manifested moderately inhibition of the activity. Since AmPR-10 had no sequence homology with other known nucleases, AmPR-10 was probably a novel nuclease. The inhibition kinetic data against papain was analyzed by Lineweaver-Burk plots, and the results showed that the inhibition of papain followed noncompetitive-type kinetics. AmPR-10 played an important role in Astragalus membranaceus defense mechanism against environmental pressure and pathogen invasion, which may be achieved by inhibiting cycteine enzymes activity.


Asunto(s)
Planta del Astrágalo/enzimología , Desoxirribonucleasas/metabolismo , Proteínas de Plantas/metabolismo , Planta del Astrágalo/genética , Cromatografía en Gel , Desoxirribonucleasas/genética , Proteínas de Plantas/genética
6.
Cereb Cortex ; 26(11): 4229-4314, 2016 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-26400918

RESUMEN

Strong perisomatic inhibition by fast-spiking basket cells (FS-BCs) regulates dentate throughput. Homotypic FS-BC interconnections that support gamma oscillations, and heterotypic inputs from diverse groups of interneurons that receive extensive neurochemical regulation, together, shape FS-BC activity patterns. However, whether seizures precipitate functional changes in inhibitory networks and contribute to abnormal network activity in epilepsy is not known. In the first recordings from dentate interneuronal pairs in a model of temporal lobe epilepsy, we demonstrate that status epilepticus (SE) selectively compromises GABA release at synapses from dentate accommodating interneurons (AC-INs) to FS-BCs, while efficacy of homotypic FS-BC synapses is unaltered. The functional decrease in heterotypic cannabinoid receptor type 1 (CB1R)-sensitive inhibition of FS-BCs resulted from enhanced baseline GABAB-mediated suppression of synaptic release after SE. The frequency of CB1R-sensitive inhibitory synaptic events in FS-BCs was depressed early after SE induction and remained reduced in epileptic rats. In biologically based simulations of heterogeneous inhibitory networks and excitatory-inhibitory cell networks, experimentally identified decrease in reliability of AC-IN to FS-BCs synaptic release reduced theta power and theta-gamma coupling and enhanced gamma coherence. Thus, the experimentally identified functional reduction in heterotypic inhibition of FS-BCs can contribute to compromised network oscillations in epilepsy and could precipitate memory and cognitive co-morbidities.

7.
Neurobiol Dis ; 89: 23-35, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26804027

RESUMEN

Altered inhibition is a salient feature of hippocampal network reorganization in epilepsy. Hippocampal pyramidal cells and dentate granule cells show specific reduction in cannabinoid receptor type 1 (CB1R)-sensitive GABAergic inputs in experimental epilepsy. In the dentate gyrus, CB1Rs regulate synaptic release from accommodating interneurons (AC-INs) with adapting firing characteristics and axonal projections in the molecular layer, but not from fast-spiking basket cells (FS-BCs). However, it is not known whether the intrinsic physiology and synaptic inhibition of AC-INs responsible for CB1R-sensitive inhibition is altered in epilepsy. Using the pilocarpine-induced status epilepticus (SE) model of epilepsy, we find that the basic physiological characteristics of AC-INs in epileptic rats are not different from age-matched controls. In paired interneuronal recordings, the amplitude of unitary inhibitory synaptic currents (uIPSCs) between AC-INs doubled after SE. Non-stationary noise analysis revealed that the post-SE strengthening of synapses between AC-INs resulted from an increase in postsynaptic receptors. Baseline synaptic release and CB1R antagonist enhancement of release at synapses between AC-INs were not different between control and post-SE rats. Additionally, uIPSC amplitude in FS-BCs to AC-INs pairs was unchanged after SE indicating input-specific microcircuit alterations in inhibitory inputs to AC-INs. At the network level, AC-INs showed no reduction in spontaneous and miniature inhibitory synaptic current (sIPSC or mIPSC) frequency or amplitude after SE. However, AC-IN mIPSC amplitude was persistently enhanced in post-SE and epileptic rats. CB1R agonist reduced the amplitude and suppressed a greater proportion of sIPSCs in AC-INs from post-SE and epileptic rats demonstrating a novel, cell-type specific increase in CB1R-sensitive inhibition of AC-INs after SE. This unique post-SE strengthening of inhibition between AC-INs could lead to activity-dependent suppression of AC-IN firing and compromise dentate CB1R-sensitive inhibition in epilepsy.


Asunto(s)
Giro Dentado/fisiopatología , Potenciales Postsinápticos Inhibidores , Interneuronas/fisiología , Receptor Cannabinoide CB1/fisiología , Estado Epiléptico/fisiopatología , Sinapsis/fisiología , Potenciales de Acción , Animales , Giro Dentado/efectos de los fármacos , Interneuronas/efectos de los fármacos , Masculino , Pilocarpina , Piperidinas/administración & dosificación , Pirazoles/administración & dosificación , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/antagonistas & inhibidores , Estado Epiléptico/inducido químicamente , Sinapsis/efectos de los fármacos
8.
Zhongguo Zhong Yao Za Zhi ; 41(10): 1876-1879, 2016 May.
Artículo en Zh | MEDLINE | ID: mdl-28895336

RESUMEN

To establish the quantitative method of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba. The contents of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba were determined by HPLC-MS. The chromatographic column was Waters XBridge Amide(4.6 mm×250 mm,5 µm). The mobile phase was acetonitrile-0.1% formic acid in gradient mode,at the flow rate of 1.0 mL• min⁻¹,with the split ratio of 1∶4. MS conditions for the ESI ion source,positive ion mode,selective ion scan(SIM) of stachydrine hydrochloride(m/z 144.0) and leonurine hydrochloride(m/z 312.0) was measured. The linear ranges of stachydrine hydrochloride was 0.562 8-281.4 µg•L-1(r=0.999 8). The linear ranges of leonurine hydrochloride was 0.521 2-260.6 µg•L-1(r=0.999 8). The method is accurate,simple,and reliable,and can be used to determine the contents of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba.


Asunto(s)
Medicamentos Herbarios Chinos/análisis , Ácido Gálico/análogos & derivados , Leonurus/química , Prolina/análogos & derivados , Cromatografía Líquida de Alta Presión , Ácido Gálico/análisis , Prolina/análisis , Espectrometría de Masas en Tándem
9.
Hippocampus ; 25(8): 884-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25603947

RESUMEN

Activity of the dentate gyrus, which gates information flow to the hippocampus, is under tight inhibitory regulation by interneurons with distinctive axonal projections, intrinsic and synaptic characteristics and neurochemical identities. Total molecular layer cells (TML-Cs), a class of morphologically distinct GABAergic neurons with axonal projections across the molecular layer, are among the most frequent interneuronal type in the dentate subgranular region. However, little is known about their synaptic and neurochemical properties. We demonstrate that synapses from morphologically identified TML-Cs to dentate interneurons are characterized by low release probability, facilitating short-term dynamics and asynchronous release. TML-Cs consistently show somatic and axonal labeling for the cannabinoid receptor type 1 (CB1 R) yet fail to express cholecystokinin (CCK) indicating their distinctive neurochemical identity. In paired recordings, the release probability at synapses between TML-Cs was increased by the CB1 R antagonist AM251, demonstrating baseline endocannabinoid regulation of TML-C synapses. Apart from defining the synaptic and neurochemical features of TML-Cs, our findings reveal the morphological identity of a class of dentate CB1 R-positive neurons that do not express CCK. Our findings indicate that TML-Cs can mediate cannabinoid sensitive feed-forward and feedback inhibition of dentate perforant path inputs.


Asunto(s)
Cannabinoides/metabolismo , Giro Dentado/citología , Interneuronas/fisiología , Inhibición Neural/fisiología , Sinapsis/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Biofisica , Moduladores de Receptores de Cannabinoides/farmacología , Colecistoquinina/metabolismo , Estimulación Eléctrica , Técnicas In Vitro , Interneuronas/efectos de los fármacos , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Inhibición Neural/efectos de los fármacos , Parvalbúminas/metabolismo , Técnicas de Placa-Clamp , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/metabolismo , Estadísticas no Paramétricas , Sinapsis/efectos de los fármacos
10.
J Vis Exp ; (204)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38407329

RESUMEN

Minimally invasive pancreatic resections are gaining popularity despite being technically demanding. However, in contrast to laparoscopic pancreatoduodenectomy (LPD), laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) has not yet obtained wide acceptance. This could be attributed to the technical challenges involved in preserving the blood supply of the duodenum and bile duct. This study describes and demonstrates all the steps of LDPPHR. A 48-year-old woman was diagnosed with a 3.0 cm x 2.5 cm pancreatic head cystic mass, which was detected unexpectedly. The surgery was performed using the 3D laparoscopy via an inferior infracolic approach. The operation lasted approximately 310 min with 100 mL of blood loss. Postoperatively, the patient experienced no complications and was discharged 5 days later. Pathology revealed intraductal papillary mucinous neoplasms. LDPPHR via an inferior infracolic approach is feasible and safe when performed by experienced surgeons in selected patients with thin mesenteric fat layers. The described technique for LDPPHR via inferior infracolic approach should be well standardized and performed at high-volume centers with experienced surgeons in both open and laparoscopic pancreatology.


Asunto(s)
Laparoscopía , Pancreatectomía , Femenino , Humanos , Persona de Mediana Edad , Páncreas/cirugía , Pancreaticoduodenectomía , Duodeno/cirugía
11.
Sleep Med ; 116: 96-104, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38437782

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep breathing disorder that is often accompanied by changes in structural connectivity (SC) and functional connectivity (FC). However, the current understanding of the interaction between SC and FC in OSA is still limited. METHODS: The aim of this study is to integrate complementary neuroimaging modalities into a unified framework using multi-layer network analysis methods and to reveal their complex interrelationships. We introduce a new graph metric called SC-FC bandwidth, which measures the throughput of SC mediating FC in a multi-layer network. The bandwidth differences between two groups are evaluated using the network-based statistics (NBS) method. Additionally, we traced and analyzed the SC pathways corresponding to the abnormal bandwidth. RESULTS: In both the healthy control and patients with OSA, the majority offunctionally synchronized nodes were connected via SC paths of length 2. With the NBS method, we observed significantly lower bandwidth between the right Posterior cingulate gyrus and right Cuneus, bilateral Middle frontal gyrus, bilateral Gyrus rectus in OSA patients. By tracing the high-proportion SC pathways, it was found that OSA patients typically exhibit a decrease in direct SC-FC, SC-FC triangles, and SC-FC quads intra- and inter-networks. CONCLUSION: Complex interrelationship changes have been observed between the SC and FC in patients with OSA, which might leads to abnormal information transmission and communication in the brain network.


Asunto(s)
Imagen por Resonancia Magnética , Apnea Obstructiva del Sueño , Humanos , Imagen por Resonancia Magnética/métodos , Apnea Obstructiva del Sueño/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Giro del Cíngulo , Mapeo Encefálico
12.
Toxics ; 12(7)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39058180

RESUMEN

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32-72.49% and 4.98-51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were <1, indicating acceptable health risks. Collectively, our innovation on cumulative risk assessment of TCM and TCM decoction provides a novel strategy with the main purpose of improving population health.

13.
J Neurophysiol ; 109(7): 1746-63, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23324316

RESUMEN

Temporal lobe epilepsy is associated with loss of interneurons and inhibitory dysfunction in the dentate gyrus. While status epilepticus (SE) leads to changes in granule cell inhibition, whether dentate basket cells critical for regulating granule cell feedforward and feedback inhibition express tonic GABA currents (I(GABA)) and undergo changes in inhibition after SE is not known. We find that interneurons immunoreactive for parvalbumin in the hilar-subgranular region express GABAA receptor (GABA(A)R) δ-subunits, which are known to underlie tonic I(GABA). Dentate fast-spiking basket cells (FS-BCs) demonstrate baseline tonic I(GABA) blocked by GABA(A)R antagonists. In morphologically and physiologically identified FS-BCs, tonic I(GABA) is enhanced 1 wk after pilocarpine-induced SE, despite simultaneous reduction in spontaneous inhibitory postsynaptic current (sIPSC) frequency. Amplitude of tonic I(GABA) in control and post-SE FS-BCs is enhanced by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), demonstrating the contribution of GABA(A)R δ-subunits. Whereas FS-BC resting membrane potential is unchanged after SE, perforated-patch recordings from FS-BCs show that the reversal potential for GABA currents (E(GABA)) is depolarized after SE. In model FS-BCs, increasing tonic GABA conductance decreased excitability when E(GABA) was shunting and increased excitability when E(GABA) was depolarizing. Although simulated focal afferent activation evoked seizurelike activity in model dentate networks with FS-BC tonic GABA conductance and shunting E(GABA), excitability of identical networks with depolarizing FS-BC E(GABA) showed lower activity levels. Thus, together, post-SE changes in tonic I(GABA) and E(GABA) maintain homeostasis of FS-BC activity and limit increases in dentate excitability. These findings have implications for normal FS-BC function and can inform studies examining comorbidities and therapeutics following SE.


Asunto(s)
Potenciales de Acción , Neuronas GABAérgicas/metabolismo , Interneuronas/metabolismo , Receptores de GABA-A/metabolismo , Estado Epiléptico/fisiopatología , Ácido gamma-Aminobutírico/metabolismo , Animales , Giro Dentado/patología , Giro Dentado/fisiopatología , Agonistas del GABA/farmacología , Neuronas GABAérgicas/fisiología , Homeostasis , Interneuronas/fisiología , Masculino , Potenciales de la Membrana , Pilocarpina/toxicidad , Ratas , Ratas Wistar , Estado Epiléptico/inducido químicamente
14.
Chaos ; 23(4): 046109, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24387588

RESUMEN

Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (E(GABA)). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (g(GABA-extra)) and experimentally identified, seizure-induced changes in g(GABA-extra) and E(GABA) influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40-100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30-40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing g(GABA-extra) reduced the frequency and coherence of FS-BC firing when E(GABA) was shunting (-74 mV), but failed to alter average FS-BC frequency when E(GABA) was depolarizing (-54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing g(GABA-extra) reduced the frequency and coherence of FS-BC firing when E(GABA) was shunting and increased average FS-BC firing when E(GABA) was depolarizing. Shifting E(GABA) from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.


Asunto(s)
Relojes Biológicos , Simulación por Computador , Modelos Neurológicos , Red Nerviosa , Convulsiones , Transmisión Sináptica , Ácido gamma-Aminobutírico/metabolismo , Ondas Encefálicas , Dendritas/metabolismo , Humanos , Red Nerviosa/metabolismo , Red Nerviosa/fisiopatología , Convulsiones/metabolismo , Convulsiones/fisiopatología
15.
Zhongguo Zhong Yao Za Zhi ; 38(11): 1731-4, 2013 Jun.
Artículo en Zh | MEDLINE | ID: mdl-24010286

RESUMEN

OBJECTIVE: To investigate the saponin in Shengmai injection. METHOD: On the basic of studing the chemical constituents of red ginseng and Shengmai injection, 20 compositions had been identifided by LC-MS/MS. RESULT: Twenty identifided compositions were the common components of Shengmai injection and red ginseng extracts. CONCLUSION: The analytical method for saponins in Shengmai injection was established which could be used as the basis for further study and quality control.


Asunto(s)
Medicamentos Herbarios Chinos/química , Saponinas/química , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Estructura Molecular
16.
bioRxiv ; 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37808695

RESUMEN

Acquired epilepsies, characterized by abnormal increase in hypersynchronous network activity, can be precipitated by various factors including brain injuries which cause neuronal loss and increases in network excitability. Electrical coupling between neurons, mediated by gap junctions, has been shown to enhance synchronous neuronal activity and promote excitotoxic neurodegeneration. Consequently, neuronal gap junctional coupling has been proposed to contribute to development of epilepsy. Parvalbumin expressing interneurons (PV-INs), noted for their roles in powerful perisomatic inhibition and network oscillations, have gap junctions formed exclusively by connexin 36 subunits which show changes in expression following seizures, and in human and experimental epilepsy. However, only a fraction of the connexin hemichannels form functional connections, leaving open the critical question of whether functional gap junctional coupling between neurons is altered during development of epilepsy. Using a pilocarpine induced status epilepticus (SE) model of acquired temporal lobe epilepsy in rat, this study examined changes in electrical coupling between PV-INs in the hippocampal dentate gyrus one week after SE. Contrary to expectations, SE selectively reduced the probability of electrical coupling between PV-INs without altering coupling coefficient. Both coupling frequency and coupling coefficient between non-parvalbumin interneurons remained unchanged after SE. The early and selective decrease in functional electrical coupling between dentate PV-INs after SE may represent a compensatory mechanism to limit excitotoxic damage of fast-spiking interneurons and network synchrony during epileptogenesis.

17.
Epilepsy Res ; 198: 107257, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37989006

RESUMEN

Acquired temporal lobe epilepsy (TLE) characterized by spontaneous recurrent seizures (SRS) and hippocampal inhibitory neuron dysfunction is often refractory to current therapies. Gap junctional or electrical coupling between inhibitory neurons has been proposed to facilitate network synchrony and intercellular molecular exchange suggesting a role in both seizures and neurodegeneration. While gap junction blockers can limit acute seizures, whether blocking neuronal gap junctions can modify development of chronic epilepsy has not been examined. This study examined whether mefloquine, a selective blocker of Connexin 36 gap junctions which are well characterized in inhibitory neurons, can limit epileptogenesis and related cellular and behavioral pathology in a model of acquired TLE. A single, systemic dose of mefloquine administered early after pilocarpine-induced status epilepticus (SE) in rat reduced both development of SRS and behavioral co-morbidities. Immunostaining for interneuron subtypes identified that mefloquine treatment likely reduced delayed inhibitory neuronal loss after SE. Uniquely, parvalbumin expressing neurons in the hippocampal dentate gyrus appeared relatively resistant to early cell loss after SE. Functionally, whole cell patch clamp recordings revealed that mefloquine treatment preserved inhibitory synaptic drive to projection neurons one week and one month after SE. These results demonstrate that mefloquine, a drug already approved for malaria prophylaxis, is potentially antiepileptogenic and can protect against progressive interneuron loss and behavioral co-morbidities of epilepsy.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Fármacos Neuroprotectores , Estado Epiléptico , Ratas , Animales , Fármacos Neuroprotectores/efectos adversos , Mefloquina/efectos adversos , Estado Epiléptico/inducido químicamente , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/patología , Convulsiones/inducido químicamente , Hipocampo , Epilepsia/patología , Pilocarpina/toxicidad , Modelos Animales de Enfermedad
18.
Brain Sci ; 13(11)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38002549

RESUMEN

Major Depressive Disorder (MDD) is a common mental illness resulting in immune disorders and even thoughts of suicidal behavior. Neuroimaging techniques serve as a quantitative tool for the assessment of MDD diagnosis. In the domain of computer-aided magnetic resonance imaging diagnosis, current research predominantly focuses on isolated local or global information, often neglecting the synergistic integration of multiple data sources, thus potentially overlooking valuable details. To address this issue, we proposed a diagnostic model for MDD that integrates high-frequency and low-frequency information using data from diffusion tensor imaging (DTI), structural magnetic resonance imaging (sMRI), and functional magnetic resonance imaging (fMRI). First, we designed a meta-low-frequency encoder (MLFE) and a meta-high-frequency encoder (MHFE) to extract the low-frequency and high-frequency feature information from DTI and sMRI, respectively. Then, we utilized a multilayer perceptron (MLP) to extract features from fMRI data. Following the feature cross-fusion, we designed the ensemble learning threshold voting method to determine the ultimate diagnosis for MDD. The model achieved accuracy, precision, specificity, F1-score, MCC, and AUC values of 0.724, 0.750, 0.882, 0.600, 0.421, and 0.667, respectively. This approach provides new research ideas for the diagnosis of MDD.

19.
Front Med (Lausanne) ; 10: 1205897, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37425297

RESUMEN

Background: The neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level are inflammatory markers related to tumor growth and metabolism. This study investigated the value of preoperative NLR, LDH and the combination of NLR and LDH (NLR-LDH) for predicting colorectal cancer liver metastasis (CRLM) and tumor prognosis in the early stages of colorectal cancer (CRC). Materials and methods: Three hundred patients undergoing CRC resection were included. Logistic regression analysis was used to estimate the correlation between CRLM time and inflammatory markers, and Kaplan-Meier survival and Cox regression analyses were used to estimate overall survival (OS). Forest plots were prepared based on the multivariate Cox analysis model and evaluated by receiver operating characteristic (ROC) curve analysis. Results: The NLR cut-off value was 2.071 according to the ROC curve. The multivariate analysis showed that the elevated LDH level and a high NLR-LDH level were independent predictors of synchronous CRLM and OS (p < 0.05). The combination of a high NLR and elevated LDH and NLR-LDH levels suggested a poor prognosis and a significantly shorter median survival time than a low NLR and low levels of LDH and NLR-LDH. The ROC curve analysis results illustrated that the predictive value of the NLR-LDH score for synchronous CRLM [area under the curve (AUC) = 0.623, p < 0.001] and OS (AUC = 0.614, p = 0.001) was superior to that of the NLR or LDH score used alone. Conclusion: LDH and NLR-LDH are reliable, easy-to-use, independent biomarkers for predicting synchronous or metachronous CRLM and OS in CRC patients. The NLR is an important monitoring index for CRLM. Preoperative NLR, LDH and NLR-LDH may help to guide the use of therapeutic strategies and cancer surveillance.

20.
Chin Med ; 18(1): 69, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37287001

RESUMEN

BACKGROUND: Heavy metals are considered a global concern because they can deteriorate human health. This guideline aims to scientifically evaluate health risk of heavy metals in TCM and to propose a reference for decision making in developing TCM-related health policies. METHODS: Using a multidisciplinary approach, a steering committee oversaw the development of the guideline. To obtain a reasonable and accurate risk assessment, key exposure assessment parameters for TCM, e.g., exposure frequency (EF), exposure duration (ED), and daily ingestion rate (IR) were obtained from surveys. In addition, transfer rates for heavy metals from Chinese medicinal materials (CMM) to decoctions or preparations were examined. RESULTS: Based on the scientific theory of risk control, the guideline was designed systematically, and principles and procedures for the risk assessment of heavy metals in TCM were identified. The guideline can be utilized to assess the risk of heavy metals in CMM and Chinese patent medicines (CPM). CONCLUSION: This guideline may help standardize the risk assessment of heavy metals in TCM, advance regulatory standards for heavy metals in TCM, and ultimately improve human health through scientific TCM usage in clinic.

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