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1.
Eur Rev Med Pharmacol Sci ; 28(6): 2363-2371, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567599

RESUMO

OBJECTIVE: Breast carcinoma in situ accounts for a significant number of newly diagnosed breast cancer cases. However, the cause of this type of cancer is unclear, which has led to debates regarding treatment strategies. A Mendelian randomization (MR) study was conducted to explore whether complement system or complement C1q/tumor necrosis factor-related proteins (CTRPs) are causally associated with breast carcinoma in situ. MATERIALS AND METHODS: This two-sample multivariable MR study used genome-wide association study (GWAS) data for all complement system factors and CTRPs. Summary-level statistics were obtained from the breast carcinoma in situ GWAS database. The study employed the MR-Egger method, inverse variance weighted (IVW) method, and weighted median method. Additionally, sensitivity analyses, including the MR-Egger intercept, funnel plot, and leave-one-out analysis, were conducted to address uncertainties and enhance the reliability of the findings. RESULTS: The study indicated that certain immunomodulatory molecules might increase the risk of breast carcinoma in situ, with consistent results. Specifically, CTRP9 showed a 57.0% increased risk [IVW: odds ratio (OR) 0.570 (0.350, 0.928), p < 0.05], and complement factor H (FH)-related protein 5 (FHR-5) was linked to a 67.2% higher risk [IVW: OR 0.672 (0.477, 0.947), p < 0.05]. However, no associations were found with other molecules, suggesting the relationship between immunomodulatory molecules and cancer may be context-specific. CONCLUSIONS: This MR study marks the initial identification of a direct link between FHR-5 and CTRP9 and the susceptibility to breast carcinoma in situ. Delving into the roles of immunomodulatory molecules and immune responses within the tumor microenvironment holds considerable importance for the management of breast carcinoma in situ.


Assuntos
Carcinoma de Mama in situ , Humanos , Complemento C1q , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Microambiente Tumoral
2.
Zhonghua Wai Ke Za Zhi ; 61(12): 1099-1103, 2023 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-37932147

RESUMO

Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (ß=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (ß=0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.


Assuntos
Neoplasias Renais , Masculino , Feminino , Humanos , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Isquemia Quente/efeitos adversos , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Rim , Isquemia/cirurgia , Taxa de Filtração Glomerular
3.
Zhonghua Zhong Liu Za Zhi ; 45(11): 981-987, 2023 Nov 23.
Artigo em Chinês | MEDLINE | ID: mdl-37968085

RESUMO

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/secundário , Metástase Linfática , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Prognóstico , Nefrectomia , Análise de Sobrevida , Necrose/patologia , Necrose/cirurgia , Taxa de Sobrevida
4.
Zhonghua Zhong Liu Za Zhi ; 45(8): 681-689, 2023 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-37580273

RESUMO

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nomogramas , Estudos Retrospectivos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Prognóstico , Fatores de Risco , Nefrectomia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Necrose
5.
Zhonghua Wai Ke Za Zhi ; 61(5): 395-402, 2023 Mar 29.
Artigo em Chinês | MEDLINE | ID: mdl-36987674

RESUMO

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

6.
Zhonghua Yan Ke Za Zhi ; 59(2): 110-117, 2023 Feb 11.
Artigo em Chinês | MEDLINE | ID: mdl-36740440

RESUMO

Objective: To compare the clinical effects of and visual quality after correction of low-degree against-the-rule (ATR) corneal astigmatism by implantation of an astigmatism-corrected intraocular lens (IOL), femtosecond laser release and manual release in cataract surgery. Methods: It was a prospective cohort study. A total of 120 patients (120 eyes) with cataract combined with low-degree ATR corneal astigmatism diagnosed in Chongqing Aier Mega Eye Hospital from December 2017 to October 2020 were included and divided into 3 groups, each with 40 patients, according to their own selections of astigmatism correction methods during cataract surgery. In the astigmatism-corrected IOL group, phacoemulsification for cataract extraction combined with toric IOL implantation was performed. In the femtosecond laser release group, astigmatic keratotomy using a femtosecond laser was combined. In the manual release group, a limbal relaxing incision was made. Uncorrected distance visual acuity (UDVA) and corneal astigmatism were measured before surgery. At 3 months and 1 year after surgery, UDVA and best-corrected distance visual acuity were examined, as well as whole eye residual astigmatism by ARK-1, corneal astigmatism by the IOLMaster 500, whole eye high order aberration (HOA) and modulation transfer function (MTF) by the iTrace visual function analyzer. Analysis of variance was used for the comparison of data in a normal distribution. Repeated measures were used for the comparison within groups. The rank sum test was used for the comparison of data that were not normally distributed. Results: Of the 120 patients, 100 patients (100 eyes), including 44 males and 56 females, with an age of (66.48±6.20) years, completed the follow-up. Among the three groups, the differences were not statistically significant in terms of gender distribution, age, preoperative corneal astigmatism, UDVA and spherical equivalent of the IOL (all P>0.05). At 3 months and 1 year after surgery, the UDVA was significantly better than that before surgery in each group (Z=5.18, 5.04, 4.98, 4.99, 4.90, 4.89; all P<0.001). At the two time points, the differences in the whole eye residual astigmatism among the three groups were statistically significant (H=30.69, 31.23; both P<0.001). At 3 months, the whole eye residual astigmatism in the astigmatism-corrected IOL group was lower than that in the other two groups. At 1 year, the residual astigmatism in the astigmatism-corrected IOL group [0.25(0.00, 0.50) D] was also lower compared to that in the femtosecond laser release group [0.50(0.50, 0.75) D] and the manual release group [0.75(0.50, 0.75) D] (Z=-3.71, -5.18, -3.94, -5.15; all P<0.001). The differences in the HOA at 3 months and 1 year among the three groups were statistically significant (H=36.30, 34.38; both P<0.001). The HOA in the astigmatism-corrected IOL group was significantly higher than that in the other two groups at the two time points (Z=5.01, 4.73, 5.31, 5.27; all P<0.001). At 3 months and 1 year, the differences in the MTF value among the three groups were also statistically significant (H=30.02, 29.92; both P<0.001), and the MTF value in the femtosecond laser release group was significantly higher than that in the other two groups (Z=4.61, 4.67, 4.66, 4.69; all P<0.001). Conclusions: All the three astigmatism correction methods used at the time of cataract surgery can effectively correct low-degree ATR corneal astigmatism. The residual astigmatism in the whole eye after astigmatism-corrected IOL implantation is small and stable, while the HOA after release using the femtosecond laser is low with good visual quality.


Assuntos
Astigmatismo , Extração de Catarata , Catarata , Doenças da Córnea , Lentes Intraoculares , Facoemulsificação , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Astigmatismo/cirurgia , Astigmatismo/diagnóstico , Implante de Lente Intraocular/métodos , Estudos Prospectivos , Refração Ocular , Facoemulsificação/métodos , Catarata/terapia , Doenças da Córnea/cirurgia
7.
Blood Cancer J ; 7(7): e588, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28753595

RESUMO

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.


Assuntos
Biomarcadores Tumorais/biossíntese , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Proteínas de Neoplasias/biossíntese , Proteína 1 Supressora da Sinalização de Citocina/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Animais Geneticamente Modificados , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Nucleofosmina , Proteína 1 Supressora da Sinalização de Citocina/genética , Taxa de Sobrevida , Peixe-Zebra , Proteínas de Peixe-Zebra/biossíntese , Proteínas de Peixe-Zebra/genética
8.
Brain Res ; 1629: 298-308, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26505917

RESUMO

Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-ß1-42 (Aß1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aß1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Peptídeos/administração & dosagem , Escopolamina/toxicidade , Animais , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Camundongos
9.
Peptides ; 71: 196-201, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26239581

RESUMO

Neuropeptide S (NPS), the endogenous ligand of NPS receptor (NPSR), was reported to be involved in the regulation of arousal, anxiety, locomotion, learning and memory. The basal ganglia play a crucial role in regulating of locomotion-related behavior. Here, we found that NPSR protein of mouse was distributed in the substantia nigra (SN) and globus pallidus (LGP) by immunohistochemical analysis. However, less is known about the direct locomotion-related effects of NPS in both SN and LGP. Therefore, we investigated the role of NPS in locomotion processes, using the open field test. The results showed that NPS infused into the SN (0.03, 0.1, 1nmol) or LGP (0.01, 0.03, 0.1nmol) dose-dependently increased the locomotor activity in mice. SHA 68 (50mg/kg), an antagonist of NPSR, blocked the locomotor stimulant effect of NPS in both nuleus. Meanwhile, these effects of NPS were also counteracted by the CRF1 receptor antagonist antalarmin (30mg/kg, i.p.). In addition, we found that the expression of c-Fos was significantly increased after NPS was delivered into SN. In conclusion, these results indicate that NPS-NPSR system may regulate locomotion together with the CRF1 system in SN.


Assuntos
Locomoção/fisiologia , Neuropeptídeos/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Substância Negra/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Neuropeptídeos/farmacologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Pirimidinas/farmacologia , Pirróis/farmacologia , Receptores de Hormônio Liberador da Corticotropina/agonistas
10.
Neurobiol Learn Mem ; 123: 187-95, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103138

RESUMO

Kisspeptin (KP), the endogenous ligand of GPR54, is a recently discovered neuropeptide shown to be involved in regulating reproductive system, anxiety-related behavior, locomotion, food intake, and suppression of metastasis across a range of cancers. KP is transcribed within the hippocampus, and GPR54 has been found in the amygdala and hippocampus, suggesting that KP might be involved in mediating learning and memory. However, the role of KP in cognition was largely unclear. Here, we investigated the role of KP-13, one of the endogenous active isoforms, in memory processes, and determined whether KP-13 could mitigate memory impairment induced by Aß1-42 in mice, using novel object recognition (NOR) and object location recognition (OLR) tasks. Intracerebroventricular (i.c.v.) infusion of KP-13 (2µg) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-improving effects of KP-13 could be blocked by the GPR54 receptor antagonist, kisspeptin-234 (234), and GnRH receptors antagonist, Cetrorelix, suggesting pharmacological specificity. Then the memory-enhancing effects were also presented after infusion of KP-13 into the hippocampus. Moreover, we found that i.c.v. injection of KP-13 was able to reverse the memory impairment induced by Aß1-42, which was inhibited by 234. To sum up, the results of our work indicate that KP-13 could facilitate memory formation and prolong memory retention through activation of the GPR54 and GnRH receptors, and suppress memory-impairing effect of Aß1-42 through activation of the GPR54, suggesting that KP-13 may be a potential drug for enhancing memory and treating Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Hipocampo/metabolismo , Kisspeptinas/farmacologia , Transtornos da Memória/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores LHRH/metabolismo , Memória Espacial/efeitos dos fármacos , Animais , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Hipocampo/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Infusões Intraventriculares , Kisspeptinas/administração & dosagem , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de Kisspeptina-1 , Receptores LHRH/antagonistas & inibidores , Reconhecimento Psicológico/efeitos dos fármacos , Retenção Psicológica/efeitos dos fármacos
11.
Behav Brain Res ; 286: 39-48, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25687846

RESUMO

Phoenixin is an amidated neuropeptide, which is widely distributed in brain and periphery regions and is known for its key role in reproduction. Phoenixin-14 (PNX-14), one of the endogenous active isoforms, was reported to regulate pituitary gonadotrophin secretion by increasing the expression of the GnRH receptor mRNA. Studies showed that GnRH could regulate brain responses to anxiety. However, the role of PNX-14 in anxiety was largely unclear. Here, we investigated that the effects of PNX-14 in anxiety-related behavior in adult mice via the open field and elevated plus maze. PNX-14 was administered intracerebroventricularly (i.c.v.) in different doses (5, 10, 25 and 50 nmol), and dose-dependently induced anxiolytic effects. Then this anxiolytic action was presented after PNX-14 injected into the anterior hypothalamic area (AHA), while PNX-14 infused into the amygdala did not exert anxiolytic effects. GnRH receptor antagonist (Cetrorelix) could significantly antagonize the anxiolytic effects of PNX-14, while Atosiban, a competitive vasopressin/oxytocin receptor antagonist could not. Moreover, PNX-14 could significantly lower the core temperature and Cetrorelix could block this effect of PNX-14. Additionally, the AHA infusion of PNX-14 (5 nmol) increased the expression level of the GnRH mRNA in the hypothalamus and plasma concentrations of GnRH. Similarly, i.c.v. injection of PNX-20 also reduced the core temperature and exerted anxiolytic effects. Taken together, centrally injected PNX-14 generates anxiolytic effects in mice, via the activation of the AHA GnRH system.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Neuropeptídeos/administração & dosagem , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiopatologia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Ansiedade/fisiopatologia , Temperatura Corporal/efeitos dos fármacos , Cateteres de Demora , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Hipotálamo Anterior/efeitos dos fármacos , Hipotálamo Anterior/fisiopatologia , Masculino , Camundongos , RNA Mensageiro/metabolismo , Receptores de Ocitocina/antagonistas & inibidores , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Vasotocina/análogos & derivados , Vasotocina/farmacologia
12.
Colorectal Dis ; 14(2): 181-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21689263

RESUMO

AIM: The aim of the study was to assess the correlation between time-intensity curve (TIC) parameters and colorectal tumour angiogenesis using double contrast-enhanced ultrasound (DCEUS), in which an intraluminal contrast agent was used in combination with an intravascular contrast agent. METHOD: Thirty nine patients with colorectal tumours were examined preoperatively. During hydrocolonal examination with the intraluminal contrast agent, an intravascular contrast agent, SonoVue, was used to perform the DCEUS. The parameter arrival time (AT), time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were measured. Postoperative specimens were assessed for microvessel density (MVD) and vascular endothelial growth factor (VEGF). The correlation between TIC parameters and the expression of VEGF or MVD was studied. RESULTS: The mean values of AT, TTP, PI and AUC of the colorectal tumours were 14.32 ± 11.36 s, 30.61 ± 18.65 s, 20.38 ± 17.45 dB and 221.10 ± 156.09 dB.s, respectively. Both AUC and MVD were significantly higher in colorectal adenocarcinomas than in adenomas (all P < 0.05). A positive linear correlation was found between the AUC and MVD in colorectal tumours (r = 0.686, P = 0.0019). No correlation was found between VEGF and any TIC parameter. CONCLUSION: DCEUS is a valuable method for evaluating angiogenesis in colorectal tumours in vivo. The AUC has a positive linear correlation with MVD and could form a new index for assessing angiogenesis and the biological behaviour of colorectal tumours.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Neovascularização Patológica/diagnóstico por imagem , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenoma/irrigação sanguínea , Adenoma/patologia , Adulto , Idoso , Área Sob a Curva , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
13.
Mycologia ; 99(1): 33-41, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17663121

RESUMO

Synchronized maturation of ascospores of Sclerotinia sclerotiorum is desirable for establishing a transformation system, conducting genetic analyses of the pathogen, defining the precise epidemiological roles of ascospores and screening plant germplasm for resistance. In general, fresh apothecia collected from germinated sclerotia contained primarily immature or discharged asci. This study was undertaken to investigate whether maturation of asci and ascospores could be enhanced by incubation of excised apothecia and to determine the effects of factors such as temperature, excision time, light and ventilation on maturation of asci and ascospores in excised apothecia. Maturation of asci was compared between intact and excised apothecia that were incubated under similar conditions. Results demonstrated that temperature was an important factor affecting ascus maturation of S. sclerotiorum during incubation of excised apothecia, and the optimum temperature was around 21 C. After incubation at 21 C for 30 h, the percentage of undischarged mature asci in excised apothecia increased up to 70-80%. This increase was accompanied by a significant increase in ascospore production of up to 5 x 10(5) ascospores per apothecium. Detailed time course studies indicated that mature asci peaked at 30-36 h of postexcision incubation. Mature asci and the number of ascospores were higher in open incubation than in closed incubation, suggesting that accumulation of volatile substances was not required for ascus/ascospore maturation during postexcision incubation and ventilation could enhance the maturation process. Light also did not affect the maturation of asci during the incubation of excised apothecia. Germination rates for ascospores from excised apothecia under various treatments were similar to those from untreated apothecia but declined slightly with time postexcision. The incubation of excised apothecia promoted ascus maturation compared with intact apothecia.


Assuntos
Ascomicetos/crescimento & desenvolvimento , Esporos Fúngicos , Ascomicetos/citologia , Luz , Viabilidade Microbiana , Morfogênese , Temperatura , Fatores de Tempo
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