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1.
Medicine (Baltimore) ; 100(36): e27178, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516515

RESUMO

ABSTRACT: Small nucleolar RNA host gene 16 (SNHG16) has recently been reported as a potential biomarker in various cancers. However, the prognostic value of SNHG16 in hepatocellular carcinoma (HCC) has not been investigated yet. Therefore, the purpose of this study was to reveal the association between SNHG16 expression and clinicopathological characteristics of HCC.Standards-compliant literature was retrieved from multiple public databases, and data on overall survival, disease-free survival, and clinicopathological characteristics related to SNGH16 were extracted and meta-analysis was performed. Additionally, the Cancer Genome Atlas data were analyzed through the gene expression profiling interactive analysis database to verify previous results.A total of 5 reports involving 410 patients with HCC were enrolled. The high expression of SNHG16 indicated worse overall survival (hazard ratio, 2.10; 95% CI, 1.22-3.60; P = .007) and disease-free survival (hazard ratio, 3.38; 95% CI, 1.10-10.40; P = .03). Additionally, the high expression of SNHG16 predicted a larger tumor size, metastasis, and advanced TNM stage.SNHG16 could serve as a potential biomarker of poor prognosis in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Prognóstico
2.
J Neurosci ; 41(37): 7727-7741, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34349001

RESUMO

Chronic itch is a troublesome condition and often difficult to cure. Emerging evidence suggests that the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) pathway may play an important role in the regulation of itch, but the cellular organization and molecular mechanisms remain incompletely understood. Here, we report that a group of RVM neurons distinctively express the G-protein-coupled estrogen receptor (GPER), which mediates descending inhibition of itch. We found that GPER+ neurons in the RVM were activated in chronic itch conditions in rats and mice. Selective ablation or chemogenetic suppression of RVM GPER+ neurons resulted in mechanical alloknesis and increased scratching in response to pruritogens, whereas chemogenetic activation of GPER+ neurons abrogated itch responses, indicating that GPER+ neurons are antipruritic. Moreover, GPER-deficient mice and rats of either sex exhibited hypersensitivity to mechanical and chemical itch, a phenotype reversible by the µ type opioid receptor (MOR) antagonism. Additionally, significant MOR phosphorylation in the RVM was detected in chronic itch models in wild-type but not in GPER-/- rats. Therefore, GPER not only identifies a population of medullary antipruritic neurons but may also determine the descending antipruritic tone through regulating µ opioid signaling.SIGNIFICANCE STATEMENT Therapeutic options for itch are limited because of an as yet incomplete understanding of the mechanisms of itch processing. Our data have provided novel insights into the cellular organization and molecular mechanisms of descending regulation of itch in normal and pathologic conditions. GPER+ neurons (largely GABAergic) in the RVM are antipruritic neurons under tonic opioidergic inhibition, activation of GPER promotes phosphorylation of MOR and disinhibition of the antipruritic GPER+ neurons from inhibitory opioidergic inputs, and failure to mobilize GPER+ neurons may result in the exacerbation of itch. Our data also illuminate on some of the outstanding questions in the field, such as the mechanisms underlying sex bias in itch, pain, and opioid analgesia and the paradoxical effects of morphine on pain and itch.

3.
CNS Neurosci Ther ; 27(11): 1313-1326, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34255932

RESUMO

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

4.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 1076-1087, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34137445

RESUMO

Propofol is the most commonly used intravenous anesthetic worldwide. It can induce loss of consciousness prior to the occurrence of severe respiratory suppression, which is also a pharmacodynamic feature of all general anesthetics. However, the neural mechanisms underlying this natural phenomenon are controversial and highly related to patient safety. In the present study, we demonstrated that the pharmacodynamic effects of propofol (50 and 100 µM) on suppression of consciousness-related excitatory postsynaptic currents in the medial prefrontal cortex (mPFC) and centromedian nucleus of the thalamus (CMT) were lower than those in the kernel respiratory rhythmogenesis nucleus pre-Bötzinger complex (PrBo). Furthermore, we unexpectedly found that the GABAA receptor ß3 subunit is the key target for propofol's action and that it is mutually and exclusively expressed in GABAergic neurons. It is also more abundant in the mPFC and CMT, but mainly co-localized with GABAergic neurons in the PrBo. As a result, the differentiated expression pattern should mediate more neuron suppression through the activation of GABAergic neurons in the mPFC and CMT at low doses of propofol (50 µM). However, PrBo GABAergic neurons were only activated by propofol at a high dose (100 µM). These results highlight the detailed pharmacodynamic effects of propofol on consciousness-related and respiration-related nuclei and provide the distinct interaction mechanism between the ß3 subunit and GABAergic neurons in mediating the suppression of consciousness compared to the inhibition of respiration.


Assuntos
Neurônios GABAérgicos/metabolismo , Núcleos Intralaminares do Tálamo , Córtex Pré-Frontal , Propofol/farmacologia , Receptores de GABA-A/metabolismo , Mecânica Respiratória/efeitos dos fármacos , Inconsciência , Animais , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/fisiopatologia , Masculino , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Ratos , Ratos Sprague-Dawley , Inconsciência/induzido quimicamente , Inconsciência/metabolismo , Inconsciência/fisiopatologia
5.
Biochem Biophys Res Commun ; 557: 69-76, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33862462

RESUMO

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 µg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of ß-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific ß-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a ß-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.


Assuntos
Ciclina D1/metabolismo , Regeneração Hepática , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Remifentanil/farmacologia , Traumatismo por Reperfusão/terapia , beta-Arrestina 2/metabolismo , Analgésicos Opioides/farmacologia , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Hepatectomia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Regulação para Cima
6.
Acta Biochim Biophys Sin (Shanghai) ; 53(5): 538-546, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33693534

RESUMO

Peripheral inflammation is always accompanied by a noxious sensation, either pain or itch, providing a protective warning for the occurrence of pathological changes; however, the mechanisms determining whether pain, itch, or both will be elicited under certain inflammatory statuses are still far from clear. Complete Freund's adjuvant (CFA) contains heat killed and dried Mycobacterium tuberculosis widely used to induce inflammatory pain models, but how CFA treatment affects itch sensation and the possible mechanisms are still unclear. In this study, using itch behavior testing and calcium imaging, we showed that both the behaviors and calcium responses associated with Transient Receptor Potential Vanilloid 1 (TRPV1)-mediated histamine-dependent itch and Transient Receptor Potential Ankyrin 1 (TRPA1)-mediated histamine-independent itch were significantly suppressed by CFA treatment. Furthermore, to explore the possible cellular mechanisms, high-throughput single-cell RNA sequencing and real-time PCR were used to detect CFA-induced changes of itch-related genes in dorsal root ganglion (DRG) neurons. Our results revealed that although both nociceptive Trpv1+ and Trpa1+ DRG neurons were increased after CFA treatment, most known pruriceptors, including Hrh1+, Mrgpra3+, Mrgprd+, Htr3a+, Htr1f+, IL31ra+, Osmr+, and Lpar3+ DRG neurons, were significantly decreased, which may explain that CFA treatment caused itch suppression. This study indicated that itch sensation was affected after CFA treatment, although negatively, and comprehensive but not specific suppression of different pruriceptors was observed after CFA treatment, suggesting that a unified adaptive change of increased pain and decreased itch will occur simultaneously under CFA-induced inflammatory conditions.


Assuntos
Adjuvante de Freund/farmacocinética , Prurido/tratamento farmacológico , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Masculino , Camundongos , Prurido/metabolismo , Prurido/patologia
7.
Acta Biochim Biophys Sin (Shanghai) ; 52(8): 864-874, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32515467

RESUMO

During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring's CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure.


Assuntos
Hipocampo , Exposição Materna/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Sevoflurano/efeitos adversos , Animais , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Sevoflurano/farmacologia
8.
J Mol Evol ; 88(2): 202-209, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31919584

RESUMO

Drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has become an increasingly serious public health problem and has complicated tuberculosis (TB) treatment. Levofloxacin (LOF) is an ideal anti-tuberculosis drug in clinical applications. However, the detailed molecular mechanisms of LOF-resistant M. tuberculosis in TB treatment have not been revealed. Our study performed transcriptome and methylome sequencing to investigate the potential biological characteristics of LOF resistance in M. tuberculosis H37Rv. In the transcriptome analysis, 953 differentially expressed genes (DEGs) were identified; 514 and 439 DEGs were significantly downregulated and upregulated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 97 pathways were enriched in this study. In the methylome analysis, 239 differentially methylated genes (DMGs) were identified; 150 and 89 DMGs were hypomethylated and hypermethylated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 74 pathways were enriched in this study. The overlap study suggested that 25 genes were obtained. It was notable that nine genes expressed downregulated mRNA and upregulated methylated levels, including pgi, fadE4, php, cyp132, pckA, rpmB1, pfkB, acg, and ctpF, especially cyp132, pckA, and pfkB, which were vital in LOF-resistant M. tuberculosis H37Rv. The overlapping genes between transcriptome and methylome could be essential for studying the molecular mechanisms of LOF-resistant M. tuberculosis H37Rv. These results may provide informative evidence for TB treatment with LOF.


Assuntos
Farmacorresistência Bacteriana/genética , Epigenoma , Levofloxacino/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Transcriptoma , Antibacterianos/farmacologia , Metilação de DNA , Genes Bacterianos
9.
Acta Biochim Biophys Sin (Shanghai) ; 51(12): 1216-1222, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31735968

RESUMO

The hypothalamus-pituitary-adrenal (HPA) axis is known to mediate gut-brain interaction, and the pathological inflammatory process in the intestine can induce HPA axis involved 'fight or flight' response to suppress or facilitate intestinal inflammation. Hypothalamic paraventricular nucleus (PVN) neurons are responsible for controlling the HPA axis activity, but their exact role in modulating intestinal inflammation remains unclear. In this study, we used the dextran sulfate sodium (DSS)-induced mice colitis model, gene editing, and RNA interference to determine the effects of PVN neurons on intestinal inflammation. We found that at the early stage (third day) after DSS treatment, there was a mild inflammation in the colorectal area and an increased neuron activation in the PVN but not in the adjacent area. At the same time, ~80% of activated PVN neurons also expressed novel estrogen GPER1 receptor. The colitis noticeably worsened in GPER1-knockout mice and local PVN GPER1-knockdown mice. These results indicated that PVN GPER1 positive neurons potentially have a protective function during the early stages of DSS-induced colitis, and this may be a mechanism by which the central nervous system attempts to suppress intestinal inflammation to achieve self-protection.


Assuntos
Colite/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Estrogênio/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-Dawley
10.
Water Sci Technol ; 79(11): 2068-2078, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31318344

RESUMO

A simple and efficient route was used to prepare an amphiphilic copolymer (poly(propylene glycol)-co-poly(ethylene glycol)-co-poly(propylene glycol)) (PPG-co-PEG-co-PPG) by one-pot polymerization reaction. This copolymer was used as the hydrophilic additive in preparation of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes via immersion-precipitation process. Surface characteristics of the membranes were confirmed by contact angle measurements, zeta potential, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. During filtration experiments, the modified membranes showed better permeation and antifouling performances compared to PVDF membranes with bovine serum albumin, sodium alginate and yeast. After hydraulic stirring cleaning with deionized water, water flux recovery and rejection ratio of the modified membranes were higher than those of pristine PVDF membrane, and the flux recovery ratio was maximized at 94.29%. It was suggested that PPG-co-PEG-co-PPG copolymer was anchored in the PVDF membrane through the two hydrophobic ends of PPG blocks, while the hydrophilic intermediate of the PEG block segregated onto the membrane or pore surface during the membrane preparation process. The synthesized method of amphiphilic PPG-co-PEG-co-PPG copolymer paved a novel way to solve the problems of less compatibility between the copolymer and membrane matrix and instability with water molecules in the ultrafiltration process.


Assuntos
Membranas Artificiais , Ultrafiltração/métodos , Permeabilidade , Polivinil
11.
Front Neurosci ; 13: 1351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920512

RESUMO

Estrogens exert extensive influences on the nervous system besides their well-known roles in regulation of reproduction and metabolism. Estrogens act via the nuclear receptor ERα and ERß to regulate gene transcription (classical genomic effects). In addition, estrogens are also known to cause rapid non-genomic effects on neuronal functions including inducing fast changes in cytosolic calcium level and rapidly desensitizing the µ type opioid receptor (MOR). The receptors responsible for the rapid actions of estrogens remain uncertain, but recent evidence points to the G protein-coupled estrogen receptor (GPER), which has been shown to be expressed widely in the nervous system. In the current study, we test the hypothesis that activation of GPER may mediate rapid calcium signaling, which may promote phosphorylation of MOR through the calcium-dependent protein kinases in neuronal cells. By qPCR and immunocytochemistry, we found that the human neuroblastoma SH-SY5Y cells endogenously express GPER and MOR. Activation of GPER by 17ß-estradiol (E2) and G-1 (GPER selective agonist) evoked a rapid calcium rise in a concentration-dependent manner, which was due to store release rather than calcium entry. The GPER antagonist G15, the PLC inhibitor U73122 and the IP3 receptor inhibitor 2-APB each virtually abolished the calcium responses to E2 or G-1. Activation of GPER stimulated translocation of PKC isoforms (α and ε) to the plasma membrane, which led to MOR phosphorylation. Additionally, E2 and G-1 stimulated c-Fos expression in SH-SY5Y cells in a PLC/IP3-dependent manner. In conclusion, the present study has revealed a novel GPER-mediated estrogenic signaling in neuroblastoma cells in which activation of GPER is followed by rapid calcium mobilization, PKC activation and MOR phosphorylation. GPER-mediated rapid calcium signal may also be transmitted to the nucleus to impact on gene transcription. Such signaling cascade may play important roles in the regulation of opioid signaling in the brain.

12.
Sensors (Basel) ; 18(6)2018 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-29865256

RESUMO

This paper proposes an effective and efficient model for concrete crack detection. The presented work consists of two modules: multi-view image feature extraction and multi-task crack region detection. Specifically, multiple visual features (such as texture, edge, etc.) of image regions are calculated, which can suppress various background noises (such as illumination, pockmark, stripe, blurring, etc.). With the computed multiple visual features, a novel crack region detector is advocated using a multi-task learning framework, which involves restraining the variability for different crack region features and emphasizing the separability between crack region features and complex background ones. Furthermore, the extreme learning machine is utilized to construct this multi-task learning model, thereby leading to high computing efficiency and good generalization. Experimental results of the practical concrete images demonstrate that the developed algorithm can achieve favorable crack detection performance compared with traditional crack detectors.

13.
Sheng Li Xue Bao ; 69(5): 532-540, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29063102

RESUMO

Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERß and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.


Assuntos
Hipertensão/etiologia , Receptores de Estrogênio/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Estresse Psicológico/complicações , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
14.
CNS Neurosci Ther ; 23(12): 980-989, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29047208

RESUMO

AIMS: Estrogens are known to exert a wide spectrum of actions on brain functions including modulation of pain. Besides the circulating estrogens produced mainly by the ovaries, many brain regions are also capable of de novo synthesizing estrogens, which may exert important modulatory effects on neuronal functions. This study was aimed to test the hypothesis that aromatase, the enzyme that catalyzes the conversion of testosterone to estradiols, may be distributed in the rostral ventromedial medulla (RVM), where it may impact on visceral pain. METHODS AND RESULTS: Adult female rats were treated with cyclophosphamide (CPM, 50 mg/kg, ip, once every 3 days) or saline. At approximately day 10 following the 3rd injection, CPM-treated rats exhibited colorectal hyperalgesia as they showed significantly greater abdominal withdrawal responses (AWR) to graded colorectal distension (CRD, 0-100 mm Hg) than the saline group. Immunofluorescent staining and Western blot assay revealed that CPM-induced colorectal hyperalgesia was associated with significantly increased expression of aromatase and phosphorylated µ-type opioid receptor (pMOR) and decreased expression of total MOR in the RVM. Intracisternal application of aromatase inhibitors, fadrozole, and letrozole reversed CPM-induced colorectal hyperalgesia and restored pMOR and MOR expression in the RVM. CONCLUSIONS: Our observations confirmed the expression of aromatase in the RVM, a pivotal brain region in descending modulation of pain and opioid analgesia. The results support the hypothesis that locally produced estrogens in the RVM may be involved in the maintenance of chronic visceral hyperalgesia and the downstream signaling may involve phosphorylation of MOR.


Assuntos
Aromatase/metabolismo , Bulbo/metabolismo , Dor Visceral/metabolismo , Dor Visceral/patologia , Animais , Antirreumáticos/toxicidade , Ciclofosfamida/toxicidade , Modelos Animais de Doenças , Feminino , Hiperalgesia/metabolismo , Limiar da Dor , Ratos , Dor Visceral/induzido quimicamente
15.
Neuroscience ; 349: 195-207, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28237817

RESUMO

The whole-cell patch-clamp technique was used to record current responses to AMPA, N-methyl-d-aspartate (NMDA), muscimol and dibenzoyl-ATP (Bz-ATP) in superficial (reactive/gliotic) substantia gelatinosa (SG) astrocytes and neurons of spinal cord slices kept for different periods of time in organotypic culture. Currents induced by AMPA, NMDA and muscimol confirmed the existence of their specific receptors in 2-week-old neurons; astrocytes cultured for the same period of time responded to AMPA and muscimol, but not to NMDA. AMPA had a larger effect on 2-week-old astrocytes than on the 1-week-old ones, in spite of a similar sensitivity of the age-matched neurons to this amino acid. The effect of the prototypic P2X7 receptor agonist Bz-ATP on superficial astrocytes and neurons depended on the drug concentration applied and increased in parallel with the lengthening of the culture period. The amplitudes of Bz-ATP currents of deep (resting) astrocytes were age-independent. Neurons located in deep layers exhibited after 1week of culturing much larger Bz-ATP currents than the superficial ones of the same age. In conclusion, whereas resting astrocytes had culture period-independent P2X7 receptor-sensitivity, reactive/gliotic astrocytes exhibited P2X7 receptor-sensitivity increasing in parallel with the prolongation of the time spent in culture. The results with Bz-ATP agree with the facilitation of AMPA-induced currents in reactive astrocytes during development, and with the hypothesis that extracellular ATP is an ontogenetically early transmitter/signaling molecule in the CNS.


Assuntos
Astrócitos/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Substância Gelatinosa/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células do Corno Posterior/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Substância Gelatinosa/efeitos dos fármacos
16.
Cereb Cortex ; 27(7): 3568-3585, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27341850

RESUMO

Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits.


Assuntos
Hipocampo/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Nucleotídeos/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2Y1/metabolismo , Estado Epiléptico/patologia , Adamantano/análogos & derivados , Adamantano/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Aminoquinolinas/farmacologia , Animais , Modelos Animais de Doenças , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Camundongos , Camundongos Transgênicos , Agonistas Muscarínicos/toxicidade , Células-Tronco Neurais/metabolismo , Pilocarpina/toxicidade , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2Y1/genética , Estado Epiléptico/induzido quimicamente
17.
J Nanosci Nanotechnol ; 13(10): 6617-26, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24245122

RESUMO

Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 (x = 0, 0.2, 0.5 and 0.8) nanoparticles are synthesized at 900 degrees C and quenched in iced water. The crystal structure, diffusion ability of lithium ions and the improved electrochemical properties are studied by X-ray diffraction, Rietveld refinement, and electrochemical techniques. The lithium diffusion ability of Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 are defined by cyclic voltammetry (CVs) profiles with various sweep rates and electrochemical impedance spectra (EIS). Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 (x = 0.2) with the biggest diffusion coefficients, delivers 254.5 mAh g(-1) and retains 90% of the initial capacity after 50 cycles. The redox peaks appeared near 3.3 V after the initial cycle, is attributed to the pair of Mn3+/Mn4+, corresponding to the improved capacity of Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 (x = 0.2). For Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 (x = 0.8) with large Cr content, the absence of the redox reaction Mn3+/Mn4+ and more inactive phase of LiCrO2 result in the lowest discharge capacity. Proper Cr substitution activates and improves the electrochemical performance of Li[Li(1/3-x/3)Cr(x)Mn(2/3-2x/3)]O2 and keeps the stable lattice structure during charge and discharge.

18.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 3): o661, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22412563

RESUMO

The title compound, C(32)H(50)O(10), prepared from a mixture of α- and ß-dihydro-artemisinin, has two ß-arteether moieties linked via an -OCH(2)CH(2)O- bridge, so that the mol-ecule is symmetric about the bridge. Each asymmetric unit contains a ß-arteether moiety and an -OCH(2) group, which is only one-half of the mol-ecule. The endo-peroxide bridges of the parent compounds have been retained in each half of the diol-bridged dimer. The rings exhibit chair and twist-boat conformations.

19.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 2): m152, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22346832

RESUMO

In the title heterodinuclear complex, [CuNa(C(8)H(7)O(3))(2)(ClO(4))(CH(3)OH)](n), the Cu(II) ion is five-coordinated by four O atoms from two 2-formyl-6-meth-oxy-phenolate anions and one O atom from a perchlorate anion in a distorted square-pyramidal geometry. The Na(+) ion is six-coordinated by four O atoms from two 2-formyl-6-meth-oxy-phenolate ligands, one O atom of a methanol mol-ecule and one O atom of a perchlorate anion. The perchlorate anions link the Na(+) and Cu(II) ions, forming a chain along [010]. O-H⋯O hydrogen bonds connect the chains. π-π inter-actions are present between the benzene rings [centroid-centroid distances = 3.566 (2) and 3.702 (2) Å]. The O atoms of the perchlorate anion are disordered over two sets of sites, with an occupancy ratio of 0.481 (8):0.519 (8).

20.
Artigo em Inglês | MEDLINE | ID: mdl-22259338

RESUMO

In the title heterodinuclear complex, [CuNa(BF(4))(C(8)H(7)O(3))(2)](n), the Cu(II) ion is four-coordinated by four O atoms of two 2-formyl-6-meth-oxy-phenolate ligands, giving rise to a square-planar geometry. The Na(+) ion is six-coordinated by four O atoms from the two ligands and two F atoms of two tetra-fluoridoborate anions. The tetra-fluoridoborate anion links the Na(+) ions, forming a one-dimensional structure along [001]. Three F atoms of the tetra-fluoridoborate anion are disordered over two sets of sites, with an occupancy ratio of 0.790 (11):0.210 (11).

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