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1.
Biochem Biophys Res Commun ; 720: 150076, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38772224

RESUMO

Chronic morphine withdrawal memory formation is a complex process influenced by various molecular mechanisms. In this study, we aimed to investigate the contributions of the basolateral amygdala (BLA) and complement component 1, q subcomponent-like 3 (C1QL3), a secreted and presynaptically targeted protein, to the formation of chronic morphine (repeat dosing of morphine) withdrawal memory using conditioned place aversion (CPA) and chemogenetic methods. We conducted experiments involving the inhibition of the BLA during naloxone-induced withdrawal to assess its impact on CPA scores, providing insights into the significance of the BLA in the chronic morphine memory formation process. We also examined changes in C1ql3/C1QL3 expression within the BLA following conditioning. Immunofluorescence analysis revealed the colocalization of C1QL3 and the G protein-coupled receptor, brain-specific angiogenesis inhibitor 3 (BAI3) in the BLA, supporting their involvement in synaptic development. Moreover, we downregulated C1QL3 expression in the BLA to investigate its role in chronic morphine withdrawal memory formation. Our findings revealed that BLA inhibition during naloxone-induced withdrawal led to a significant reduction in CPA scores, confirming the critical role of the BLA in this memory process. Additionally, the upregulation of C1ql3 expression within the BLA postconditioning suggested its participation in withdrawal memory formation. The colocalization of C1QL3 and BAI3 in the BLA further supported their involvement in synaptic development. Furthermore, downregulation of C1QL3 in the BLA effectively hindered chronic morphine withdrawal memory formation, emphasizing its pivotal role in this process. Notably, we identified postsynaptic density protein 95 (PSD95) as a potential downstream effector of C1QL3 during chronic morphine withdrawal memory formation. Blocking PSD95 led to a significant reduction in the CPA score, and it appeared that C1QL3 modulated the ubiquitination-mediated degradation of PSD95, resulting in decreased PSD95 protein levels. This study underscores the importance of the BLA, C1QL3 and PSD95 in chronic morphine withdrawal memory formation. It provides valuable insights into the underlying molecular mechanisms, emphasizing their significance in this intricate process.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Proteína 4 Homóloga a Disks-Large , Memória , Morfina , Síndrome de Abstinência a Substâncias , Animais , Morfina/farmacologia , Síndrome de Abstinência a Substâncias/metabolismo , Masculino , Camundongos , Memória/efeitos dos fármacos , Proteína 4 Homóloga a Disks-Large/metabolismo , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Complemento C1q/metabolismo , Camundongos Endogâmicos C57BL , Naloxona/farmacologia
2.
Mol Psychiatry ; 29(3): 793-808, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145987

RESUMO

Context-induced retrieval of drug withdrawal memory is one of the important reasons for drug relapses. Previous studies have shown that different projection neurons in different brain regions or in the same brain region such as the basolateral amygdala (BLA) participate in context-induced retrieval of drug withdrawal memory. However, whether these different projection neurons participate in the retrieval of drug withdrawal memory with same or different molecular pathways remains a topic for research. The present results showed that (1) BLA neurons projecting to the prelimbic cortex (BLA-PrL) and BLA neurons projecting to the nucleus accumbens (BLA-NAc) participated in context-induced retrieval of morphine withdrawal memory; (2) there was an increase in the expression of Arc and pERK in BLA-NAc neurons, but not in BLA-PrL neurons during context-induced retrieval of morphine withdrawal memory; (3) pERK was the upstream molecule of Arc, whereas D1 receptor was the upstream molecule of pERK in BLA-NAc neurons during context-induced retrieval of morphine withdrawal memory; (4) D1 receptors also strengthened AMPA receptors, but not NMDA receptors, -mediated glutamatergic input to BLA-NAc neurons via pERK during context-induced retrieval of morphine withdrawal memory. These results suggest that different projection neurons of the BLA participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Morfina , Neurônios , Núcleo Accumbens , Síndrome de Abstinência a Substâncias , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Masculino , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/fisiopatologia , Morfina/farmacologia , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Memória/fisiologia , Receptores de AMPA/metabolismo , Ratos , Dependência de Morfina/metabolismo , Tonsila do Cerebelo/metabolismo , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Vias Neurais/metabolismo , Córtex Pré-Frontal/metabolismo
3.
Animals (Basel) ; 13(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37508118

RESUMO

Habitat loss and human threats are putting the marbled polecat (Vormela peregusna) on the brink of extinction. Numerous recent studies have found that climate change will further deteriorate the living environment of endangered species, leading to their eventual extinction. In this study, we used the results of infrared camera surveys in China and worldwide distribution data to construct an ensemble model consisting of 10 commonly used ecological niche models to specify potential suitable habitat areas for V. peregusna under current conditions with similar environments to the sighting record sites. Changes in the suitable habitat for V. peregusna under future climate change scenarios were simulated using mid-century (2050s) and the end of the century (2090s) climate scenarios provided by the Coupled Model Intercomparison Project Phase 6 (CMIP6). We evaluated the accuracy of the model to obtain the environmental probability values (cutoff) of the V. peregusna distribution, the current distribution of suitable habitats, and future changes in moderately and highly suitable habitat areas. The results showed that the general linear model (GLM) was the best single model for predicting suitable habitats for V. peregusna, and the kappa coefficient, area under the curve (AUC), and true skill statistic (TSS) of the ensemble model all exceeded 0.9, reflecting greater accuracy and stability than single models. Under the current conditions, the area of suitable habitat for V. peregusna reached 3935.92 × 104 km2, suggesting a wide distribution range. In the future, climate change is predicted to severely affect the distribution of V. peregusna and substantially reduce the area of suitable habitats for the species, with 11.91 to 33.55% of moderately and highly suitable habitat areas no longer suitable for the survival of V. peregusna. This shift poses an extremely serious challenge to the conservation of this species. We suggest that attention be given to this problem in Europe, especially the countries surrounding the Black Sea, Asia, China, and Mongolia, and that measures be taken, such as regular monitoring and designating protected areas for the conservation of vulnerable animals.

4.
Clin Pharmacol Drug Dev ; 12(3): 324-332, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36642942

RESUMO

The main objective of this study was to compare the pharmacokinetic (PK) bioequivalence of two capecitabine tablets and explore the different PK profiles of various tumors in Chinese patients with cancer. All 76 patients with a confirmed cancer diagnosis were included in this study. A single dose of 2000 mg of test or reference capecitabine (Xeloda, Hoffmann-La Roche) was orally administered postprandially. After 24 hours of washout, the patients were administered the test or the reference capecitabine alternately. PK samples were taken at the time of predose up to 6 hours postdose. Bioequivalence evaluation was performed using the geometric mean ratios of peak concentration in plasma (Cmax) , area under the concentration-time curve from time 0 to 6 h (AUC0-t) , and area under the concentration-time curve from time 0 to infinity (AUC0-∞ ) for capecitabine and 5-fluorouracil (5-FU). In this study, 90% confidence intervals of test/reference mean ratios of Cmax , AUC0-t , AUC0-∞ of capecitabine and 5-FU were in the range of 80%-125%. Both the test and reference capecitabine regimens were well tolerated in this study. Furthermore, we found that patients with esophageal-gastrointestinal cancers had higher exposure to capecitabine and a shorter time to Cmax (Tmax) than those with breast cancer. In conclusion, a single oral dose of 2000 mg of test capecitabine tablets after postprandial administration was bioequivalent to the reference drug.


Assuntos
Capecitabina , Neoplasias , Humanos , Área Sob a Curva , Disponibilidade Biológica , Capecitabina/farmacocinética , População do Leste Asiático , Fluoruracila , Neoplasias/tratamento farmacológico , Comprimidos
5.
Nat Commun ; 14(1): 71, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604429

RESUMO

The lateral hypothalamus (LH) is physiologically critical in brain functions. The LH also plays an important role in drug addiction. However, neural circuits underlying LH involvement of drug addiction remain obscure. In the present study,our results showed that in male mice, during context-induced expression of morphine withdrawal memory, LH glutamatergic neurons played an important role; dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) projecting from the core of nucleus accumbens (NAcC) to the LH were an important upstream circuit to activate LH glutamatergic neurons; D1-MSNs projecting from the NAcC to the LH activated LH glutamatergic neurons through inhibiting LH local gamma-aminobutyric acid (GABA) neurons. These results suggest that disinhibited LH glutamatergic neurons by neural circuits from the NAcC importantly contribute to context-induced the expression of morphine withdrawal memory.


Assuntos
Morfina , Transtornos Relacionados ao Uso de Substâncias , Camundongos , Masculino , Animais , Morfina/efeitos adversos , Núcleo Accumbens/metabolismo , Região Hipotalâmica Lateral/metabolismo , Neurônios/metabolismo , Receptores de Dopamina D1/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo
6.
Transl Psychiatry ; 12(1): 458, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316324

RESUMO

Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.


Assuntos
MicroRNAs , Morfina , Córtex Pré-Frontal , Fatores de Transcrição , Animais , Ratos , Regulação da Expressão Gênica , MicroRNAs/genética , Morfina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Fatores de Transcrição/metabolismo
7.
J Am Coll Cardiol ; 80(6): 584-594, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35926931

RESUMO

BACKGROUND: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily. OBJECTIVES: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF. METHODS: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32. RESULTS: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm. CONCLUSIONS: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).


Assuntos
Fármacos Cardiovasculares , Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Benzazepinas/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca , Humanos , Ivabradina/uso terapêutico , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Função Ventricular Esquerda
9.
Mar Pollut Bull ; 179: 113708, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35533618

RESUMO

The contents of chemothermal oxidation (CTO)-derived black carbon (BC) and organic carbon (OC) and their stable isotopes (δ13CBC and δ13COC), including major elemental oxides, and grain sizes were measured to constrain the sources, burial flux, and mass inventory of BC in surface sediments of the Daya Bay. Surface sediments were mainly clayey silt (>90%) and contained 0.28-1.18% OC and 0.05-0.18% BC. Fossil fuel emission and physical erosion contributed to the sedimentary BC sources. High BC/OC ratio (6-30%), burial flux (154.88-922.67 µg cm-2 y-1), and mass inventory (22-34 Gg y-1) of BC in the upper 5 cm of surface sediments indicated that the Daya Bay is a significant sink of BC. The high accumulation of BC in sediments is attributed to a strong affinity to fine-grained sediments due to the enrichment of muddy biodeposits excrements from the cultured species in the bay.


Assuntos
Baías , Sedimentos Geológicos , Sepultamento , Carbono/análise , China , Monitoramento Ambiental , Fuligem/análise
10.
Front Mol Neurosci ; 14: 720371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531724

RESUMO

Rac1 is a small GTPase of the Rho family. A previous study showed that the activation of Rac1 had an opposing effect on induction and maintenance of long-term potentiation (LTP) in the hippocampus. However, the molecular mechanism underlying this opposing effect remains to be addressed. In the present work, we find that the activation of Rac1 during the induction of LTP leads to an activation of PKCι/λ by phosphatidylinositol-3-kinase (PI3K), whereas the activation of Rac1 during the maintenance of LTP leads to the inhibition of PKMζ by LIM_kinase (LIMK) in the hippocampus. This result suggests that during different stages of LTP, the activation of Rac1 can modulate different signaling pathways, which leads to an opposing effect on the induction and maintenance of LTP in the hippocampus.

11.
Front Pharmacol ; 12: 660541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149414

RESUMO

Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects. Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial. Results: Cmax and AUC0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC0-∞ was 88.58%. These evaluation indexes are in the standard range of 80-125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar. Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.

12.
Sci Total Environ ; 783: 146899, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-33865127

RESUMO

Surface sediment samples were collected from Daya Bay in October 2018, and analyzed for total organic carbon (OC), total nitrogen (TN) and their stable isotopes (δ13C and δ15N), total phosphorus (TP), biogenic silica (BSi), sediment textures and specific surface area (SSA). The primary objective was to evaluate the influence of mariculture/aquaculture on the distribution characteristics of organic matter (OM), and preservation status of OC, TN, TP, and BSi in sediments. The average δ13C and δ15N values, and OC/TN ratios were -21.27‰, 6.74‰, and 8.90, respectively. Monte Carlo simulation results revealed that mariculture/aquaculture biodeposits accounted for >40% of the buried OM at sites where the breeding rafts and cages are located, whereas marine OM increased gradually to the open sea. Terrestrial OM was generally low accounting for 17% by average. The contents and distribution characteristics of biogenic elements were more influenced by mariculture/aquaculture and primary productivity than sediment textures. Lower OC/SSA (0.3-1.2 mg OC/m2), TN/SSA (~0.05-0.18 mg TN/m2), and TP/SSA (0.02-0.04 mg TP/m2) loadings indicated that increased sequestration of labile OM in a coastal bay could contribute to significant degradation of recalcitrant OM in sediments with significant loss of P relative to OC. Nitrogen contamination in surface sediments was due to increased injection of aquaculture biodeposits, and may pose a detrimental effect on the ecological sustainability of the bay. Higher BSi/SSA loadings (0.9-1.7 mg BSi/m2) revealed that BSi was more preserved, and that BSi-based proxy could be used for paleo-productivity studies. However, such preservation may induce adverse dissolved silicate limitation in a bay perturbed by eutrophication. Fine-grained sediments (clay and silt) accounted for >77% of the sediment texture types with higher SSA, and while controlling the contents of biogenic elements under given depositional conditions were not the main determining factors of OC, TN, TP, and BSi preservation.

13.
Cell Rep ; 35(1): 108958, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33826893

RESUMO

Previous work has shown that the paraventricular nucleus of the thalamus (PVT) is an important region that is involved in the conditioned context-induced retrieval of morphine withdrawal memory. However, the upstream neural circuits that activate the PVT to participate in the conditioned context-induced retrieval of morphine withdrawal memory remain unknown. In the present work, we find that the conditioned context activates projection neurons from the prelimbic cortex (PrL) to the PVT, and the inhibition of PrL-PVT projection neurons inhibits the conditioned context-induced retrieval of morphine withdrawal memory; the conditioned context induces an increase in Arc expression, intrinsic excitability, and glutamate output in PrL-PVT projection neurons in morphine-withdrawn mice. These results suggest that the activity of PrL-PVT projection neurons is necessary for the retrieval of morphine withdrawal memory, and the conditioned context causes a plastic change in the activity in these projection neurons during the withdrawal memory retrieval.


Assuntos
Memória/fisiologia , Rememoração Mental , Núcleos da Linha Média do Tálamo/fisiologia , Morfina/efeitos adversos , Córtex Pré-Frontal/fisiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Condicionamento Clássico , Proteínas do Citoesqueleto/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia
14.
Environ Sci Pollut Res Int ; 28(20): 25858-25865, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33479873

RESUMO

In this study, the concentrations of 16 kinds of polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Daya Bay were determined and analyzed. Results showed that 16 PAHs were detected in all the samples, and the total PAH concentration ranged from 70.18 to 128.04 ng g-1, with an average of 103.17 ng g-1. The cyclic number distribution of PAHs in the sediments was mainly 4 and 5 rings. Six classic PAH ratios named Ant/(Ant + Phe), Fla/(Fla + Pyr), [InP/(InP + BghiP)], [BaA/(BaA + Chr)], BaA/BghiP, and LMW/HMW, and principal component analyses showed that the main source of PAHs in this region was combustion (biomass, coal, and petroleum combustion), and the secondary source was petroleum. The ecological risk analysis of PAHs by using effect range low/median method and mean effects range-median quotient method showed that all of PAHs are lower than the effect range low (ERL) level and the effects range-median quotient (M-ERM-Q) value of all stations is 0.0027-0.0067, with an average value of 0.0046. Thus, it can be seen that PAHs are at a low-risk level in surface sediments of Daya Bay.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Baías , China , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Poluentes Químicos da Água/análise
15.
Exp Neurol ; 338: 113600, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33453215

RESUMO

Drug relapse can be mainly ascribed to the retrieval of drug withdrawal memory induced by conditioned context. Previous studies have shown that the central nucleus of the amygdala lateral division (CeL) could be activated by conditioned context. However, what source of input that activates the CeL during conditioned context-induced retrieval of morphine-withdrawal memory remains unknown. In this study, using retrograde labeling, immunohistochemistry, local microinjection and chemogenetic technologies, we found that (1) Conditioned context induced an activation of the CeL and the inhibition of the CeL inhibited the context-induced retrieval of morphine-withdrawal memory; (2) the inhibition of the paraventricular nucleus of thalamus (PVT) or PVT-CeL projection neurons caused an attenuation of the activation of the CeL by conditioned context and conditioned place aversion (CPA); (3) the inhibition of the locus coeruleus (LC) or LC-CeL projection neurons decreased the activation of the CeL by conditioned context and CPA. These results suggest that the CeL is necessary for conditioned context-induced retrieval of morphine-withdrawal memory and inputs from PVT and LC contribute to the activation of the CeL during context-induced retrieval of morphine withdrawal memory.


Assuntos
Núcleo Central da Amígdala/fisiopatologia , Locus Cerúleo/fisiopatologia , Memória/fisiologia , Núcleos da Linha Média do Tálamo/fisiopatologia , Dependência de Morfina/fisiopatologia , Animais , Condicionamento Psicológico/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/fisiopatologia , Síndrome de Abstinência a Substâncias/fisiopatologia
16.
Front Neurosci ; 14: 646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760235

RESUMO

Conditioned context-induced retrieval of drug withdrawal memory contributes to drug relapse. The basolateral amygdala (BLA) is an important brain region that is involved in conditioned context-induced retrieval of morphine withdrawal memory. However, the upstream pathways of the activation of the BLA by conditioned context remains to be studied. The present results show that the CA1 of dorsal hippocampus is an upstream brain region of the activation of the BLA during conditioned context-induced morphine withdrawal memory retrieval; the indirect connection from the CA1 of dorsal hippocampus to the BLA is enhanced in mice with conditioned place aversion (CPA); the postrhinal cortex (POR) is a brain region that connects the CA1 of dorsal hippocampus and the activation of the BLA during conditioned context-induced retrieval of morphine-withdrawal memory. These results suggest that a conditioning-strengthened indirect circuit from the CA1 of dorsal hippocampus to the BLA through the POR participates in morphine withdrawal memory retrieval.

17.
Neuropharmacology ; 176: 108217, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32679049

RESUMO

Ventral tegmental area (VTA) dopamine (DA) neurons presynaptic glutamate release plays a very important role in the mechanism of morphine. Previously, a study from our lab found that morphine disinhibited glutamatergic input onto the VTA-DA neurons, which was an important mechanism for the morphine-induced increase in the VTA-DA neuron firing and related behaviors (Chen et al., 2015). However, what source of glutamatergic inputs is disinhibited by morphine remains to be elucidated. Using optogenetic strategy combined with whole-cell patch-clamp, qRT-PCR, immunofluorescence and chemical genetic approach combined with behavioral methods, our results show that: 1) morphine promotes glutamate release from glutamatergic terminals of medial prefrontal cortex (mPFC) neurons projecting to VTA-DA neurons but does not on those from glutamatergic terminals of the lateral hypothalamus (LH) neurons projecting to VTA-DA neurons; 2) different response of glutamatergic neurons projecting to VTA-DA neurons from the mPFC or the LH to morphine is related to the expression of GABAB receptors at terminals of these neurons; 3) inhibition of projection neurons from the mPFC to the VTA significantly reduces morphine-induced locomotor activity increase and conditioned place preference but inhibition of projection neurons from the LH to the VTA does not. These results suggest that morphine selectively promotes glutamate release of the glutamatergic input from mPFC onto VTA-DA neurons by removing the inhibition of the GABAB receptors in this glutamatergic input from mPFC.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Ácido Glutâmico/metabolismo , Morfina/administração & dosagem , Córtex Pré-Frontal/metabolismo , Recompensa , Área Tegmentar Ventral/metabolismo , Analgésicos Opioides/administração & dosagem , Animais , Neurônios Dopaminérgicos/química , Neurônios Dopaminérgicos/efeitos dos fármacos , Ácido Glutâmico/análise , Injeções Intraventriculares , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Córtex Pré-Frontal/química , Córtex Pré-Frontal/efeitos dos fármacos , Área Tegmentar Ventral/química , Área Tegmentar Ventral/efeitos dos fármacos
18.
Clin Pharmacol Drug Dev ; 9(4): 505-513, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31553134

RESUMO

Azilsartan (AZL), the active metabolite of azilsartan medoxomil, is the newest angiotensin receptor blocker that has been approved for the treatment of hypertension in 2012 in Japan. The present study aimed to evaluate the safety and pharmacokinetic properties of AZL in healthy Chinese subjects. We performed 2 phase 1 studies to investigate the pharmacokinetics and safety of AZL in healthy Chinese adults after a single dose (20 mg or 40 mg) or multiple doses of AZL (40 mg/d for 7 days; Study I) and after a single 40-mg dose under the fasted and fed conditions (Study II). Noncompartmental analysis and nonlinear mixed-effects modeling were used to analyze the pharmacokinetic properties of AZL. Twenty-seven healthy volunteers (14 men and 13 women) aged 20-32 years were enrolled and completed the study. During single dosing of AZL, the pharmacokinetics of AZL exhibited a linear profile between dosage and area under the concentration-time curve. There is no AZL accumulation after multiple doses. Food had no effect on the pharmacokinetic characteristics of AZL. AZL concentrations were best fit with a 2-compartment model, and the typical value of clearance was 1.63 L/h. Body weight had an impact on both the apparent clearance and peripheral volume of distribution. The pharmacokinetic parameters were consistent with previous studies in non-Chinese subjects. Model-based simulations indicated that a 45-kg subject would have approximately double the AZL exposure of a 90-kg subject. Whether the exposure difference has clinical significance needs to be confirmed in further studies among patients.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Povo Asiático , Benzimidazóis/administração & dosagem , Interações Alimento-Droga , Oxidiazóis/administração & dosagem , Adulto , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacocinética , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Modelos Biológicos , Oxidiazóis/efeitos adversos , Oxidiazóis/farmacocinética , Distribuição Tecidual , Adulto Jovem
19.
Vector Borne Zoonotic Dis ; 20(3): 231-235, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31589566

RESUMO

Toxoplasma gondii is one of protozoan parasites resulting in zoonosis, which can infect nearly all of warm-blooded hosts, including humans and raccoon dogs (Nyctereutes procyonoides). However, related reports on prevalence and genetic characterization of T. gondii strains in raccoon dogs were few in China. The aim of this study was to survey the prevalence and genetic characterization of T. gondii strains in domestic raccoon dogs from Jilin, Liaoning, and Hebei provinces, northern China. During April 2016 to November 2017, a total of 337 tissue samples collected from domestic raccoon dogs were detected with B1 gene using a nested PCR. And the positive samples were genotyped at 11 genetic markers (SAG1, 5'-and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus PCR-restriction fragment length polymorphism technology. Sixteen out of 337 sika deer (4.75%) were positive with B1 gene by nest PCR. Furthermore, four positive DNA samples were completely typed through further being genotyped, in which three samples were identified as ToxoDB Genotype #9, and one sample was confirmed as ToxoDB Genotype #10. The results of molecular detection not only revealed the existence of T. gondii in domestic raccoon dogs in Jilin, Liaoning, and Hebei for the first time, but also provided the information of genetic diversity. This study also indicated that ToxoDB Genotype #9 as a kind of potential reservoir for T. gondii transmission, may be main genotype in domestic raccoon dogs in China, posing a risk of infection in human health.


Assuntos
Cães Guaxinins/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/parasitologia , Animais , China/epidemiologia , DNA de Protozoário/genética , Genótipo , Prevalência , Toxoplasma/genética , Toxoplasmose Animal/epidemiologia
20.
Mar Pollut Bull ; 141: 61-69, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955774

RESUMO

This study presents the distribution, seasonal variations and factors influencing phosphorus (P) forms in surface sediments from the Maowei Sea. P forms were measured using the sequential extraction (SEDEX) procedures. Inorganic P (IP) was the predominant chemical form of total P (TP). Fe-bound P (FeP) was the main IP form. Sediment particle sizes, organic matter distribution, terrestrial input and aquaculture activity were responsible for the seasonal variations of different forms of P in sediment. In summer, the average proportions of P fractions in TP followed the order of organic P (OP) > Fe-P > authigenic P (CaP) > detrital P (De-P) > exchangeable P (Ex-P); in winter, the corresponding order was OP > Fe-P > De-P > Ca-P > Ex-P. The potential bio-available P accounted for 71.1 ±â€¯4.9% and 70.6 ±â€¯6.3% of TP in summer and winter, respectively. Sedimentary organic matter mainly came from land-based sources in winter.


Assuntos
Sedimentos Geológicos/análise , Fósforo/análise , Aquicultura , Disponibilidade Biológica , China , Monitoramento Ambiental , Sedimentos Geológicos/química , Ferro/análise , Ferro/química , Tamanho da Partícula , Fósforo/química , Fósforo/farmacocinética , Estações do Ano
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