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1.
EMBO Rep ; 24(10): e56098, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37522391

RESUMO

A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11-SDH ) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1+ ) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor-expressing (GRPR+ ) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch.


Assuntos
Receptores da Bombesina , Medula Espinal , Humanos , Receptores da Bombesina/genética , Receptores da Bombesina/metabolismo , Peptídeo Liberador de Gastrina/genética , Peptídeo Liberador de Gastrina/metabolismo , Medula Espinal/metabolismo , Ácido Glutâmico/metabolismo , Dopamina/metabolismo , Prurido/genética , Prurido/metabolismo , Neurônios Dopaminérgicos/metabolismo , Receptores de AMPA/genética , Receptores de AMPA/metabolismo
2.
Lipids Health Dis ; 23(1): 201, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937844

RESUMO

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.


Assuntos
Aldo-Ceto Redutases , Curcumina , Hepatopatia Gordurosa não Alcoólica , Triglicerídeos , Curcumina/farmacologia , Curcumina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Humanos , Células Hep G2 , Aldo-Ceto Redutases/metabolismo , Ratos , Masculino , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/metabolismo , Aldeído Redutase/metabolismo , Aldeído Redutase/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Simulação de Acoplamento Molecular , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metformina/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Rodanina/análogos & derivados , Tiazolidinas
3.
BMC Med Educ ; 24(1): 386, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589890

RESUMO

BACKGROUND: Medical students face a heavy burden as they are tasked with acquiring a vast amount of medical knowledge within a limited time frame. Self-directed learning (SDL) has become crucial for efficient and ongoing learning among medical students. However, effective ways to foster SDL ability among Chinese medical students are lacking, and limited studies have identified factors that impact the SDL ability of medical students. This makes it challenging for educators to develop targeted strategies to improve students' SDL ability. This study aims to assess SDL ability among Chinese medical students and examine the effects of career calling and teaching competencies on SDL ability, as well as the possible mechanisms linking them. METHODS: Data were collected from 3614 respondents (effective response rate = 60.11%) using cross-sectional online questionnaires and analyzed using IBM SPSS Statistics 22.0. The questionnaire comprised a Demographic Characteristics Questionnaire, Self-directed Learning Ability Scale (Cronbach's alpha = 0.962), Teaching Competencies Scale, and Career Calling Scale. RESULTS: The average SDL ability score of Chinese medical students was 3.68 ± 0.56, indicating a moderate level of SDL ability. The six factors of the Self-directed Learning Ability Scale-self-reflection, ability to use learning methods, ability to set study plans, ability to set studying objectives, ability to adjust psychological state, and willpower in studying-accounted for 12.90%, 12.89%, 12.39%, 11.94%, 11.34%, and 8.67% of the variance, respectively. Furthermore, career calling was positively associated with SDL learning ability (ß = 0.295, p < 0.001), and SDL learning ability was positively associated with teaching competencies (ß = 0.191, p < 0.01). Simple slope analysis showed that when the level of teaching competencies was higher, the influence of career calling on SDL ability was stronger. CONCLUSIONS: Chinese medical students' SDL ability has room for improvement. Medical students could strengthen their willpower in studying by setting milestones goals with rewards, which could inspire their motivation for the next goals. Teachers should guide students to learn experience to improve students' reflective ability. Educators play a crucial role in bridging the gap between career calling education and SDL ability enhancement, highlighting the significance of optimal teaching competencies. Colleges should focus on strengthening teachers' sense of career calling and teaching competencies.


Assuntos
Educação Médica , Estudantes de Medicina , Humanos , Estudos Transversais , Estudantes de Medicina/psicologia , Currículo , China
4.
Zhonghua Nan Ke Xue ; 30(3): 272-276, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-39177396

RESUMO

Prostate cancer (PCa) is currently the second most common malignancy in men worldwide,and its incidence rate is on the rise. Most cases of PCa are treated by radical prostatectomy, but with the development of medical imaging and innovation in therapeutic theories and technology, focal therapy has shown better application prospects in the treatment of PCa. Compared with radical prostatectomy, focal therapy yields satisfactory results in terms of effectiveness and reduction of complications in addition to avoidance of overtreatment and treatment-related financial burden. This article reviews the strategies of focal therapy for PCa, including cryoablation, high-intensity focused ultrasound, irreversible electroporation, and photodynamic therapy, with an analysis of the clinical trials in recent years.


Assuntos
Criocirurgia , Fotoquimioterapia , Neoplasias da Próstata , Humanos , Neoplasias da Próstata/terapia , Masculino , Fotoquimioterapia/métodos , Criocirurgia/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Prostatectomia/métodos , Eletroporação/métodos
5.
Angew Chem Int Ed Engl ; 63(14): e202317922, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38366167

RESUMO

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

6.
Opt Lett ; 48(6): 1347-1350, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36946924

RESUMO

We demonstrate sub-Rayleigh dark-field imaging via speckle illumination. Imaging is achieved with second-order autocorrelated measurement by illuminating objects with hollow conical pseudothermal light. Our scheme can work well for highly transparent amplitude objects, pure phase objects, and even more complex transparent objects. The autocorrelated dark-field images show better resolution than intensity-averaged images and an ability in filtering out low-frequency noises.

7.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373296

RESUMO

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Animais , Camundongos , Gânglios Espinais/metabolismo , Hiperalgesia/genética , Hiperalgesia/metabolismo , Neuralgia/etiologia , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Potássio/metabolismo , RNA Interferente Pequeno/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Potássio Shal/metabolismo
8.
Opt Express ; 30(4): 6248-6257, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209564

RESUMO

By the method of singular-valued decomposition (SVD), ghost imaging (GI) reconstructs the images with high efficiency. However, a small amount of noise can greatly degrade or even destroy the object information. In this paper, we experimentally investigate the method of truncated SVD (TSVD) by selecting the first few largest singular values to enhance the image quality. The contrast-to-noise ratio and structural similarity of the images are improved with appropriate truncation ratios. To further improve the image quality, we analyze the noise effects on TSVD-based GI and introduce additional filters. TSVD-based GI may find its applications in rapid imaging under complicated environment conditions.

9.
Cell Mol Neurobiol ; 42(5): 1543-1555, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33694132

RESUMO

Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be expressed in spinal astrocytes and is involved in neuropathic pain. In this study, we investigated the role and mechanism of TRAF6 in complete Freund's adjuvant (CFA)-evoked chronic inflammatory hypersensitivity and the effect of docosahexaenoic acid (DHA) on TRAF6 expression and inflammatory pain. We found that TRAF6 was dominantly increased in microglia at the spinal level after intraplantar injection of CFA. Intrathecal TRAF6 siRNA alleviated CFA-triggered allodynia and reversed the upregulation of IBA-1 (microglia marker). In addition, intrathecal administration of DHA inhibited CFA-induced upregulation of TRAF6 and IBA-1 in the spinal cord and attenuated CFA-evoked mechanical allodynia. Furthermore, DHA prevented lipopolysaccharide (LPS)-caused increase of TRAF6 and IBA-1 in both BV2 cell line and primary cultured microglia. Finally, intrathecal DHA reduced LPS-induced upregulation of spinal TRAF6 and IBA-1, and alleviated LPS-induced mechanical allodynia. Our findings indicate that TRAF6 contributes to pain hypersensitivity via regulating microglial activation in the spinal dorsal horn. Direct inhibition of TRAF6 by siRNA or indirect inhibition by DHA may have therapeutic effects on chronic inflammatory pain.


Assuntos
Dor Crônica , Neuralgia , Animais , Dor Crônica/metabolismo , Adjuvante de Freund/metabolismo , Adjuvante de Freund/toxicidade , Hiperalgesia/metabolismo , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Neuralgia/metabolismo , RNA Interferente Pequeno/metabolismo , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia
10.
J Nurs Manag ; 30(6): 1396-1406, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33794045

RESUMO

AIM: This study aimed to (1) assess the current status of Chinese nurses' exposure to workplace violence; (2) identify the cluster of interrelationships between abusive supervision, anxiety and depression symptoms, work ability, and workplace violence in nursing settings; and (3) clarify the functional mechanism among these variables. METHODS: A cross-sectional survey was conducted online from September to October 2020 in China. A total of 1,221 valid questionnaires were collected across 100 cities in 31 provinces. RESULTS: Approximately 67.57% of participants experienced workplace violence in the past one year, in the types of verbal violence (59.71%), made difficulties (43.16%), mobbing behaviour (26.70%), smear reputation (22.52%), physical violence (11.30%), intimidating behaviour (10.16%) and sexual harassment (4.10%), respectively. Moreover, nurses' exposure to workplace violence was significantly and positively influenced by the perceptions of abusive supervision (ß = 0.209, p < .01) and the symptoms of anxiety and depression (ß = 0.328, p < .01). Anxious and depressive symptoms partly mediated the association between abusive supervision and workplace violence, which were significantly moderated by work ability (ß = -0.021, p < .05). CONCLUSIONS: Our study assesses the prevalence of the seven types of workplace violence against Chinese nurses. Majority of nurses have experienced different types of workplace violence. Nurses who are abused by their supervisor are more likely to develop poor psychological health than those who are not. Moreover, nurses' positive association of abusive supervision with workplace violence is more notable among nurses with lower work ability. IMPLICATIONS OF NURSING MANAGEMENT: 'No abusive supervision, no workplace violence'. A harmonious nursing environment needs to be provided to minimize exposure to workplace violence and mental health threats towards nursing staff, which is a key point for hospital administrators and health policymakers. Essential work ability should be developed to reduce the damage of the abusive supervision and workplace violence against nurses.


Assuntos
Recursos Humanos de Enfermagem Hospitalar , Violência no Trabalho , Ansiedade , Estudos Transversais , Humanos , Saúde Mental , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários , Violência no Trabalho/psicologia
11.
Zhonghua Nan Ke Xue ; 28(8): 715-721, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37838972

RESUMO

As the incidence of prostate cancer (PCa) increases with the aging of men, more and more attention is paid to the prevention and treatment of the pregnancy. In addition to widely used PSA test, MRI and other diagnostic strategies, PCa-related gene screening, with the development of such new technologies as second-generation gene sequencing, is more and more applied in the detection of PCa. Different types of tumor-related genes have different effects on the development and progression of PCa as well as different values in the diagnosis, treatment and prognosis of the malignancy. This review focuses on the advances in the studies of PCa-related critical genes and key gene pathways.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Prognóstico , Imageamento por Ressonância Magnética , Envelhecimento
12.
Zhonghua Nan Ke Xue ; 28(3): 239-242, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-37462963

RESUMO

Approximately 10-15% of the cases of male infertility worldwide are caused by obstructive azoospermia. Vasovasostomy (VV) is a gold-standard treatment of this disease, but the success rate of conventional VV remains low for failure to anastomose the vas deferens accurately. Fortunately, microscopy makes the field of vision clearer and greatly increases the success rate of vas deferens recanalization and pregnancy. VV under the microscope, including microsurgical VV, robot-assisted microsurgical VV, and laparoscope-assisted microsurgical VV, is of great importance for the treatment of male infertility. This article reviews the progress in the study of VV under the microscope.


Assuntos
Azoospermia , Vasovasostomia , Gravidez , Feminino , Masculino , Humanos , Vasovasostomia/efeitos adversos , Microscopia , Ducto Deferente/cirurgia , Azoospermia/etiologia , Microcirurgia/efeitos adversos
13.
Opt Lett ; 46(19): 4900-4903, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598229

RESUMO

We propose and experimentally demonstrate a high-efficiency single-pixel imaging (SPI) scheme by integrating time-correlated single-photon counting (TCSPC) with time-division multiplexing to acquire full-color images at an extremely low light level. This SPI scheme uses a digital micromirror device to modulate a sequence of laser pulses with preset delays to achieve three-color structured illumination, then employs a photomultiplier tube into the TCSPC module to achieve photon-counting detection. By exploiting the time-resolved capabilities of TCSPC, we demodulate the spectrum-image-encoded signals, and then reconstruct high-quality full-color images in a single round of measurement. Based on this scheme, strategies such as single-step measurement, high-speed projection, and undersampling can further improve imaging efficiency.

14.
Opt Express ; 28(25): 37167-37176, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33379555

RESUMO

Ghost imaging is a promising technique for shape reconstruction using two spatially correlated beams: one beam interacts with a target and is collected with a bucket detector, and the other beam is measured with a pixelated detector. However, orthodox ghost imaging always provides unsatisfactory results for unstained samples, phase objects, or highly transparent objects. Here we present a dark-field ghost imaging technique that can work well for these "bad" targets. The only difference from orthodox ghost imaging is that the bucket signals rule out the target's unscattered beam. As experimental proof, we demonstrate images of fine copper wires, quartz fibers, scratched and damaged glass plates, a pure phase object, and biospecimens.

15.
BMC Cancer ; 20(1): 220, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171265

RESUMO

BACKGROUND: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute. METHODS: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters. RESULTS: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients. CONCLUSION: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/fisiopatologia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/fisiopatologia , Idoso , China/epidemiologia , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/epidemiologia
16.
J Neurosci ; 38(49): 10535-10551, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30373770

RESUMO

G-protein-coupled receptors are considered to be cell-surface sensors of extracellular signals, thereby having a crucial role in signal transduction and being the most fruitful targets for drug discovery. G-protein-coupled receptor 151 (GPR151) was reported to be expressed specifically in the habenular area. Here we report the expression and the epigenetic regulation of GRP151 in the spinal cord after spinal nerve ligation (SNL) and the contribution of GPR151 to neuropathic pain in male mice. SNL dramatically increased GPR151 expression in spinal neurons. GPR151 mutation or spinal inhibition by shRNA alleviated SNL-induced mechanical allodynia and heat hyperalgesia. Interestingly, the CpG island in the GPR151 gene promoter region was demethylated, the expression of DNA methyltransferase 3b (DNMT3b) was decreased, and the binding of DNMT3b with GPR151 promoter was reduced after SNL. Overexpression of DNMT3b in the spinal cord decreased GPR151 expression and attenuated SNL-induced neuropathic pain. Furthermore, Krüppel-like factor 5 (KLF5), a transcriptional factor of the KLF family, was upregulated in spinal neurons, and the binding affinity of KLF5 with GPR151 promoter was increased after SNL. Inhibition of KLF5 reduced GPR151 expression and attenuated SNL-induced pain hypersensitivity. Further mRNA microarray analysis revealed that mutation of GPR151 reduced the expression of a variety of pain-related genes in response to SNL, especially mitogen-activated protein kinase (MAPK) signaling pathway-associated genes. This study reveals that GPR151, increased by DNA demethylation and the enhanced interaction with KLF5, contributes to the maintenance of neuropathic pain via increasing MAPK pathway-related gene expression.SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) are targets of various clinically approved drugs. Here we report that SNL increased GPR151 expression in the spinal cord, and mutation or inhibition of GPR151 alleviated SNL-induced neuropathic pain. In addition, SNL downregulated the expression of DNMT3b, which caused demethylation of GPR151 gene promoter, facilitated the binding of transcriptional factor KLF5 with the GPR151 promoter, and further increased GPR151 expression in spinal neurons. The increased GPR151 may contribute to the pathogenesis of neuropathic pain via activating MAPK signaling and increasing pain-related gene expression. Our study reveals an epigenetic mechanism underlying GPR151 expression and suggests that targeting GPR151 may offer a new strategy for the treatment of neuropathic pain.


Assuntos
Desmetilação , Fatores de Transcrição Kruppel-Like/metabolismo , Neuralgia/metabolismo , Regiões Promotoras Genéticas/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Medula Espinal/metabolismo , Animais , Sequência de Bases , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Neuralgia/genética , Neuralgia/patologia , Ligação Proteica/fisiologia , Receptores Acoplados a Proteínas G/genética , Medula Espinal/patologia
17.
J Cell Biochem ; 120(10): 17757-17766, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31144384

RESUMO

BACKGROUND/AIMS: High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. METHODS: The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. RESULTS: As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p. CONCLUSION: HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.


Assuntos
Inativação Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , RNA Longo não Codificante/genética
18.
BMC Cancer ; 19(1): 871, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477094

RESUMO

BACKGROUND: The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. METHODS: Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. RESULTS: Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12-1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10-1.28) and sisters only (RR 1.71, 95% CI 1.43-2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74-4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04-1.34) with low-quality evidence. CONCLUSIONS: This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Núcleo Familiar , Neoplasias da Próstata/epidemiologia , Risco
19.
BMC Med Educ ; 19(1): 211, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196065

RESUMO

BACKGROUND: Medical students struggle with a heavy workload during their comparatively long course of study in China. The future of medical science depends largely on whether or not medical students become qualified. This study aims to explore whether medical students' academic adaptability affects learning outcomes. This paper will not only provide scientific evidence for educators and administrators of medical schools but will also benefit students by improving their aptitude and adaptability through a thorough discussion on their educational environment. METHODS: We conducted a cross-sectional survey from September to December 2016. A total of 1977 respondents completed the questionnaire with a response rate of 79.08%. A cross-sectional survey was used in this study. Descriptive statistics, factor analysis, General Linear Model (GLM) analysis, standard multiple regression, and hierarchical multiple regression were performed for data analysis using the Statistical Package for Social Sciences software (SPSS Version 19.0, SPSS Inc., Chicago, IL, USA). RESULTS: Out of the 1977 students, 1586 (80.2%) had mean academic adaptability levels over 3. Findings suggested that academic adaptability (Mean = 3.32), immersion in learning (Mean = 3.20), and academic performance (Mean = 3.39), were at the middle level while academic burnout (Mean = 2.17) was at a low level. Academic adaptability of medical students showed a significant negative relation to academic burnout (Beta = - 0.705, P<0.01), there was a significant positive relation between academic adaptability and immersion in learning (Beta = 0.655, P<0.01) and academic performance (Beta = 0.407, P<0.01). CONCLUSIONS: Higher levels of academic adaptability are associated with lower levels of burnout and higher levels of immersion in learning and academic performance. It might be helpful for medical schools to consider academic adaptability and ways of enhancing such skills in order to enhance student performance and engagement while in school.


Assuntos
Desempenho Acadêmico/psicologia , Esgotamento Psicológico , Aprendizagem , Estudantes de Medicina/psicologia , Adolescente , China , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
20.
Zhonghua Nan Ke Xue ; 25(3): 265-271, 2019 Mar.
Artigo em Zh | MEDLINE | ID: mdl-32216246

RESUMO

Prostate cancer is a most common malignant tumor in the male urogenital system. Currently, castration-resistant prostate cancer (CRPC) is a bottleneck in the treatment of prostate cancer, which has a very poor prognosis, with a median survival of merely 12 months. Although androgen-deprivation therapy eliminates the majority of the androgens in circulation, CRPC patients adapt to low-level androgens by synthesizing intratumoral androgens or altering androgen receptors. This review summarizes the main ways of synthesizing testosterone and dihydrotestosterone (DHT), the enzymes involved, and changes of the androgen level in different stages of CRPC. Blocking any one of the pathways of androgen biosynthesis is likely to upregulate another and lead to incomplete androgen elimination and consequently drug resistance. Therefore, identifying the pathways of androgen biosynthesis may provide an opportunity for the development of the drugs for blocking the major pathways of androgen and introtumoral androgen biosynthesis and antagonizing androgen receptors.


Assuntos
Androgênios/biossíntese , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos , Di-Hidrotestosterona , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos , Testosterona/biossíntese
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