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BACKGROUND: Interferon stimulated exonuclease gene 20 (ISG20) has been reported to be correlated with macrophage infiltration in glioblastoma (GBM) in previous bioinformatics-based studies. This study explores the exact effect of ISG20 on macrophage polarization in GBM. METHODS: ISG20 expression in GBM tissues and cells was determined by RT-qPCR and/or immunohistochemistry. GBM cells were co-cultured with M0 macrophages (PMA-stimulated THP-1 cells) in vitro, followed by flow cytometry and ELISA to analyze the M2 polarization of macrophages. Fluorescence-contained GBM cells were intracranially injected into nude mice along with M0 macrophages to generate orthotopic xenograft tumor models. Upstream regulator of ISG20 was predicted using bioinformatics. Loss- or gain-of-function assays of Fos like 2 (FOSL2) and ISG20 were performed in GBM cells. DNA methylation level of FOSL2 was analyzed by bisulfite sequencing analysis. RESULTS: ISG20 was found highly expressed in GBM tissues and cells. ISG20 silencing in GBM cells decreased CD206 and CD163 levels in the co-cultured macrophages and reduced secretion of IL-10 and TGF-ß. It also enhanced survival of nude mice bearing xenograft tumors, blocked tumor growth, and suppressed M2 polarization of macrophages in vivo. FOSL2, highly expressed in GBM, bound to the ISG20 promoter to activate its transcription. FOSL2 silencing similarly blocked M2 polarization of macrophages, which was negated by ISG20 overexpression. The high FOSL2 expression in GBM was attributed to DNA hypomethylation. CONCLUSION: This study demonstrates that FOSL2 is highly expressed in GBM due to DNA hypomethylation. It activates transcription of ISG20, thus promoting M2 polarization of macrophages and GBM development.
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Neoplasias Encefálicas , Glioblastoma , Macrófagos , Camundongos Nus , Humanos , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Animais , Macrófagos/metabolismo , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Exonucleases/metabolismo , Exonucleases/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Carcinogênese/genética , Proliferação de Células , ExorribonucleasesRESUMO
M1-like macrophages have been reported to play critical roles in acute kidney injury (AKI). Here, we elucidated the role of ubiquitin-specific protease 25 (USP25) in M1-like macrophages polarization and AKI. High USP25 expression was correlated with a decline in renal function in patients with acute kidney tubular injury and in mice with AKI. In contrast, USP25 knockout reduced M1-like macrophage infiltration, suppressed M1-like polarization, and improved AKI in mice, indicating that USP25 was necessary for M1-like polarization and proinflammatory response. Immunoprecipitation assay and liquid chromatography-tandem mass spectrometry showed that the M2 isoform of pyruvate kinase, muscle (PKM2) was a target substrate of USP25. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated the USP25 regulated aerobic glycolysis and lactate production during M1-like polarization via PKM2. Further analysis showed that the USP25-PKM2-aerobic glycolysis axis positively regulated M1-like polarization and exacerbated AKI in mice, providing potential therapeutic targets for AKI treatment.
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Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , Piruvato Quinase/metabolismo , Rim/metabolismo , Macrófagos/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia/metabolismo , Músculos , Reperfusão , Glicólise , Camundongos Endogâmicos C57BL , Ubiquitina Tiolesterase/metabolismoRESUMO
Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.
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Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Suínos/genética , Animais , Estudo de Associação Genômica Ampla/veterinária , Fenótipo , Genômica , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Aquaporin 4 (AQP4), usually expressed at astrocytes end-feet, is a main component of the lymph-lymphatic system and promotes paravascular cerebrospinal fluid-interstitial fluid exchange. Moreover, angiotensin II type 1 (AT1) receptor affects amyloid ß (Aß) levels. This study aimed to detect the effect of AT1 receptor deficiency on the blood-brain barrier (BBB) of traumatic brain injury (TBI) mice and the effect on Aß level and glial lymphatic circulation. METHODS: TBI model was built using AT1 receptor knockout mice (AT1-KO) and C57BL/6 mice (wild type, WT). BBB integrity was detected by Evans blue extravasation. The expression of the astrocytic water channel AQP4 and astrocyte activation were evaluated with immunofluorescence. The expressions of amyloid precursor protein (APP), junction protein zonula occludens protein-1 (ZO-1) and occludin in mice brain were detected by Western blot (WB). Aß levels were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: AT1 receptor deficiency defended BBB integrity and rescued occludin and ZO-1 decrease in mice brain induced by TBI. AT1-KO mice had less increase of APP expression and Aß 1-42, Aß 1-40 levels compared to WT mice under TBI. Moreover, AT1 receptor deficiency was found to significantly inhibit AQP4 depolarization after TBI. CONCLUSION: T1 receptor deficiency attenuated TBI-induced impairments of BBB by rescuing tight junction proteins and inhibited AQP4 polarization, thus improving the function of glymphatic system to enhance interstitial Aß clearance in TBI mice brain.
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Barreira Hematoencefálica , Receptor Tipo 1 de Angiotensina , Receptor Tipo 1 de Angiotensina/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Ocludina/metabolismo , Ocludina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Aquaporina 4/metabolismo , Animais , CamundongosRESUMO
AIMS: Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression. METHODS AND RESULTS: From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3high group (34 patients) and a glomerular C3low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3low group. Renal biopsies in the C3high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-γ than those in the C3low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease. CONCLUSIONS: A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.
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Complemento C3/metabolismo , Glomerulonefrite por IGA/patologia , Glomérulos Renais/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/mortalidade , Humanos , Rim/metabolismo , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear. AQP4-/- and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Brain edema and Evans blue extravasation were conducted 24 h post-injury to evaluate the acute TBI. Morris water maze (MWM) was used to establish the long-term cognitive functions of AQP4-/- and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-ß clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay. AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-ß clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation. AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.
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Aquaporina 4/deficiência , Lesões Encefálicas Traumáticas/metabolismo , Neuroproteção/fisiologia , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Edema Encefálico/etiologia , Edema Encefálico/metabolismo , Lesões Encefálicas Traumáticas/complicações , Progressão da Doença , Sistema Glinfático/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos Knockout , Teste do Labirinto Aquático de Morris/fisiologiaRESUMO
BACKGROUND: Circular RNAs (circRNAs) play an important role in the tumorigenesis of glioma. Our study indicated that low hsa_circ_0008225 expression was associated with poor overall survival in patients with glioma. However, the relevant mechanism of hsa_circ_0008225 in glioma tumorigenesis remains unclear. METHODS: Two datasets (GSE86202 and GSE92322) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed circRNAs (DEcircRNAs) between glioma tissues and matched normal tissues were screened using R language. RESULTS: A total of 79 overlapping DEcircRNAs were identified by comparison of glioma and matched normal tissues. In addition, low hsa_circ_0008225 expression was associated with poor overall survival in patients with glioma. Overexpression of hsa_circ_0008225 markedly inhibited the proliferation, migration and invasion of SHG44 cells via inducing apoptosis. Mechanically, overexpression of hsa_circ_0008225 increased the expression of miR-890 targeted gene ZMYND11 via acting as a competitive 'sponge' of miR-890. CONCLUSION: Our results suggested that hsa_circ_0008225 functions as a tumor inhibitor in glioma by sponging miR-890 and then promoting the function of ZMYND11. Therefore, hsa_circ_0008225 could be a potential prognostic biomarker for the treatment of glioma.
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Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica/genética , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glioma/genética , Glioma/patologia , MicroRNAs , RNA Circular/fisiologia , Apoptose/genética , Movimento Celular/genética , Expressão Gênica , Glioma/mortalidade , Humanos , Invasividade Neoplásica/genética , RNA Circular/genética , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND AND AIMS: In this observational cohort study, we assessed the prognostic value of DC-SIGN+ cells in the pathogenesis and progression of IgA nephropathy (IgAN). METHODS AND RESULTS: A total of 139 adult IgAN patients were enrolled into this study from June 2009 to June 2010. We characterised DC-SIGN+ cells by immunohistochemistry or immunofluorescence in renal biopsy tissue. Correlations between the DC-SIGN, intercellular adhesion molecule 3 (ICAM-3), CD4 and CD8 were evaluated. Patients were classified into the DC-SIGNhigh and DC-SIGNlow groups. Depending on an average of 100-month follow-up, the predictive value of DC-SIGN+ cells in IgAN progression was analysed. DC-SIGN+ cells were found frequently in IgAN kidneys while rarely observed in normal kidneys, and almost all DC-SIGN+ cells expressed MHC-II. We also found that DC-SIGN+ cells were adjacent to ICAM-3-positive CD4+ and CD8+ lymphocytes. The density of DC-SIGN+ cells was positively and linearly correlated with the density of ICAM-3+ cells, CD4+ cells and CD8+ cells in renal biopsy tissues. In the DC-SIGNhigh group, the degree of renal lesion and inflammatory cell infiltration was more severe compared to the DC-SIGNlow group. Patients in the DC-SIGNhigh group also had increased incidences of deteriorating renal function during the follow up compared to patients in the DC-SIGNlow group. CONCLUSIONS: DC-SIGN+ cells probably served as a potential contributor to exacerbate local inflammatory response. The density of DC-SIGN+ cells was associated with the severity of renal lesions of the patients. High renal DC-SIGN+ cell density might be used as a predictor of poor prognosis in patients with IgAN.
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Moléculas de Adesão Celular/metabolismo , Células Dendríticas/patologia , Glomerulonefrite por IGA/patologia , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Antígenos CD/biossíntese , Biópsia , Moléculas de Adesão Celular/biossíntese , Contagem de Células , China , Células Dendríticas/metabolismo , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/terapia , Antígenos de Histocompatibilidade Classe II/biossíntese , Hospitais Universitários , Humanos , Inflamação/patologia , Estimativa de Kaplan-Meier , Rim/citologia , Rim/patologia , Modelos Lineares , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Terapia de Substituição Renal , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Linfócitos T/metabolismoRESUMO
BACKGROUND: Cardiovascular disease (CVD) events are the main cause of death in long-term hemodialysis (HD) patients. Macrophage colony- stimulating factor (M-CSF) is actively involved in the formation of atherosclerosis and causes plaque instability, thrombosis and the development of acute coronary syndromes. However, little information is available on the role of M-CSF in HD patients. We aimed to investigate the association between plasma M-CSF levels and CVD events as well as all-cause mortality in patients undergoing long-term HD. METHODS: Fifty two HD patients and 8 healthy controls were recruited in this study. HD patients were followed up from September 2014 to May 2017. The primary end point was CVD event, the secondary outcome was death from any cause. Patients were divided into two groups with low and high M-CSF levels based on the optimal cut-off value determined by the ROC curve. Cox regression analyses were used to assess the predictive value of plasma M-CSF for CVD events and all-cause mortality in HD patients. We tested the levels of plasma M-CSF and other inflammatory cytokines in surviving HD patients using ELISA or CBA kit. RESULTS: The average plasma level of M-CSF in 52 patients was approximately twice that of healthy controls (992.4 vs. 427.2 pg/mL; p < 0.05). During 32 months of follow-up, 26 patients (50.0%) had at least one CVD event and 8 patients (15.4%) died. The mean plasma M-CSF concentration increased in survivors after follow-up compared to that detected at baseline (1277.8 ± 693.3 vs. 997.2 ± 417.4 pg/mL; p < 0.05). Multivariate Cox regression analysis showed that plasma M-CSF is an independent risk factor for CVD events in HD patients (p < 0.05). In the Cox regression model after adjusting for gender and age, high M-CSF levels were related to an increased risk of all-cause death (p < 0.05). We also found that M-CSF levels were positively correlated with IL-6 and IL-18 levels (both p < 0.05), which are the major pathogentic cytokines that contribute to HD-related CVD events. CONCLUSION: M-CSF is a prognostic factor for CVD events and all-cause mortality in HD patients.
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Doenças Cardiovasculares/etiologia , Fator Estimulador de Colônias de Macrófagos/sangue , Diálise Renal/mortalidade , Fatores Etários , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Estudos de Casos e Controles , Causas de Morte , Feminino , Humanos , Interleucina-18/sangue , Interleucina-6/sangue , Interleucinas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Valores de Referência , Análise de Regressão , Diálise Renal/efeitos adversos , Fatores Sexuais , Fator de Necrose Tumoral alfa/sangueRESUMO
Many systems are dynamic and time-varying in the real world. Discovering the vital nodes in temporal networks is more challenging than that in static networks. In this study, we proposed a temporal information gathering (TIG) process for temporal networks. The TIG-process, as a node's importance metric, can be used to do the node ranking. As a framework, the TIG-process can be applied to explore the impact of temporal information on the significance of the nodes. The key point of the TIG-process is that nodes' importance relies on the importance of its neighborhood. There are four variables: temporal information gathering depth n, temporal distance matrix D, initial information c, and weighting function f. We observed that the TIG-process can degenerate to classic metrics by a proper combination of these four variables. Furthermore, the fastest arrival distance based TIG-process ( fad-tig) is performed optimally in quantifying nodes' efficiency and nodes' spreading influence. Moreover, for the fad-tig process, we can find an optimal gathering depth n that makes the TIG-process perform optimally when n is small.
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AIM: the number of intestinal IgA+ lymphocytes are decreased in acute liver necrosis and the mechanism remains poorly understood. The purpose of this study was to observe the role of lymphocyte homing and apoptosis associated with decreased intestinal IgA positive lymphocytes in acute liver necrosis. METHODS: the acute liver necrosis mouse model and LTßR pre-treatment were used to assess intestinal mucosal addressin cell adhesion molecule-1 (MAdCAM - 1) expression, cell apoptosis, IgA+ cells and secretory immunoglobulin A (SIgA). RESULTS: MAdCAM - 1 mRNA and protein expression decreased significantly in the acute necrosis group; 0.57 ± 0.032 fold vs. baseline (p < 0.05) and 0.45 ± 0.072 fold vs. baseline (p < 0.05), respectively. LTßR pre-treatment could significantly improve the decline of MAdCAM - 1 mRNA and protein expression in the intestinal mucosa (1.83 ± 0.064 fold vs. baseline, p < 0.05 and 1.75 ± 0.046 fold vs. baseline, p < 0.05, respectively) and partially restore the decline in IgA+ lymphocytes and SIgA levels. There were increased rates of enterocyte apoptosis in both the acute liver necrosis and LTßR pre-treatment group; 0.79% vs. control (p < 0.05) and 0.77% vs. control (p < 0.05), respectively). CONCLUSION: our results suggest that the dysfunction of lymphocyte homing and apoptosis are both involved with decreased intestinal IgA+ lymphocytes in acute liver necrosis. LTßR pre-treatment can partially restore IgA+ cells and SIgA by increasing MAdCAM - 1 expression, rather than inhibiting lymphocyte apoptosis.
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Moléculas de Adesão Celular/análise , Movimento Celular/fisiologia , Imunoglobulina A/análise , Fígado/patologia , Linfócitos/fisiologia , Mucoproteínas/análise , Alanina Transaminase/sangue , Animais , Apoptose , Aspartato Aminotransferases/sangue , Moléculas de Adesão Celular/genética , Movimento Celular/imunologia , Modelos Animais de Doenças , Enterócitos/fisiologia , Imunidade nas Mucosas/imunologia , Imunoglobulina A Secretora/análise , Marcação In Situ das Extremidades Cortadas , Fígado/imunologia , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucoproteínas/genética , Necrose/imunologia , Necrose/patologia , RNA Mensageiro/análiseRESUMO
Resveratrol is a naturally occurring phytoalexin found in red grapes, and believed to have neuroprotective, anti-oxidant, and anti-inflammatory effects. But little is known about its effect on the neural impairments induced by microglial over-activation, which leads to neuroinflammation and multiple pathophysiological damages. In this study, we aimed to investigate the protective effects of resveratrol on the impairments of neural development by microglial over-activation insult. The results indicated that resveratrol inhibited the lipopolysaccharide (LPS)-dependent release of cytokines from activated microglia and LPS-dependent changes in NF-κB signaling pathway. Conditioned medium (CM) from activated microglia treated by resveratrol directly protected primary cultured hippocampal neurons against LPS-CM-induced neuronal death, and restored the inhibitory effects of LPS-CM on dendrite sprouting and outgrowth. Finally, neurons cultured in CM from LPS-stimulated microglia treated by resveratrol exhibited increased spine density compared to those without resveratrol treatment. Our findings support that resveratrol inhibits microglial over-activation and alleviates neuronal injuries induced by microglial activation. Our study suggests the use of resveratrol as an alternative intervention approach that could prevent further neuronal insults.
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Hipocampo/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estilbenos/farmacologia , Animais , Animais Recém-Nascidos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , ResveratrolRESUMO
The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of 120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.
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Neoplasia Prostática Intraepitelial , Neoplasias da Próstata , Masculino , Humanos , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasia Prostática Intraepitelial/tratamento farmacológico , Finasterida/farmacologia , Finasterida/uso terapêutico , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Progressão da DoençaRESUMO
Objective: This study investigated the efficacy of different concentrations of Cholesterol-loaded cyclodextrin (CLC) on cryopreservation in boar sperm quality. Methods: In this study, we treated boar sperm with different concentrations of CLC before freezing and analyzed the sperm cholesterol concentration, plasma membrane, acrosome integrity rate and total motility rate before and after freeze-thawing. We also investigated the levels of reactive oxygen species (ROS), malondialdehyde (MDA), ATP, and structural- and oxidative-damage related proteins in all groups after thawing. Results: The results revealed that the cholesterol concentration of the CLC-treated groups was higher than that of the control group, both before freezing and after thawing (p < 0.05). The plasma membrane integrity rate, acrosome integrity rate, and total motility rate of sperm were also enhanced after thawing in the CLC-treated group (all p < 0.05). Moreover, ROS and MDA production and ATP loss were reduced in CLC-treated sperm during freezing and thawing (p < 0.05). Finally, CLC pretreatment partially prevented the consumption of various proteins involved in metabolism including CAPZB, HSP90AA1 and PGAM2 (p < 0.05). Conclusion: CLC treatment increased cholesterol concentration and decreased structural injury and oxidative damage during boar sperm freezing and thawing, improving the efficacy of sperm cryopreservation in boar.
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BACKGROUND: At present, there is no unified and effective treatment for extreme corrosive esophageal stenosis (CES) with esophagotracheal fistula (ETF). This case had extreme and severe esophageal stenosis (ES) and ETF after ingesting an enzyme-based chemical detergent, resulting in a serious pulmonary infection and severe malnutrition. Upper gastrointestinal imaging showed that he had an ETF, and endoscopy showed that he had extreme and severe esophageal stricture. This case was complex and difficult to treat. According to the domestic and foreign literature, there is no universal treatment that is low-risk. CASE SUMMARY: A patient came to our hospital with extreme ES, an ETF, and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzyme-based detergent. The ES was serious, and the endoscope was unable to pass through the esophagus. We treated him by endoscopic incision method (EIM), esophageal stent placement (ESP), and endoscopic balloon dilation (EBD) by using the bronchoscope and gastroscope. This treatment not only closed the ETF, but also expanded the esophagus, with minimal trauma, greatly reducing the pain of the patient. According to the literature, there are no similar reported cases. CONCLUSION: We report, for the first time, a patient with extreme CES complicated with ETF, where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM, ESP, and EBD.
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Objective: To explore the spatial relationship between A1 segment proximal anterior cerebral artery aneurysms and their main trunks, classify them anatomically and develop targeted treatment strategies. Methods: This single-center retrospective analysis involved 39 patients diagnosed with aneurysms originating from the proximal of A1 segment of the anterior cerebral artery (2014-2023). Classify the patient's aneurysm into 5 types based on the location of the neck involving the carrier artery and the spatial relationship and projection direction of the aneurysm body with the carrier artery, and outcomes from treatment methods were compared. Results: Among 39 aneurysms, 18 cases underwent endovascular intervention treatment, including 6 cases of stent assisted embolization, 1 case of flow-diverter embolization, 5 cases of balloon assisted embolization, and 6 cases of simple coiling. At discharged, the mRS score of all endovascularly treated patients was 0, and the GOS score was 5 at 6 months after discharge. At discharge, the mRS score of microsurgical clipping treated patients was 0 for 15 cases, 3 for 1 case, 4 for 1 case and 5 for 2 cases. Six months after discharge, the GOS score was 5 for 16 cases, 4 for 2 cases, 3 for 2 cases, and 1 for 1 case. GOS outcomes at 6 months were better for endovascularly treated patients (p = 0.047). Conclusion: Results showed better outcomes for the endovascular treatment group compared to microsurgical clipping at 6 months after surgery. The anatomical classification of aneurysms in this region may be of help to develop effective treatment strategies.
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In this study, we examined the effectiveness of percutaneous injected fibrin glue as a treatment for frontal sinus cerebrospinal fluid (CSF) rhinorrhea in a series of 4 cases. All 4 patients had fracture in the posterior wall of the frontal sinus. The anterior wall of the frontal sinus was punctured following high-resolution computed tomography imaging. In 3 out of 4 patients with defective skull due to prior frontal craniotomy, direct percutaneous puncture of the frontal sinus was used. Fibrin glue was injected to close the fistula and to seal the rhinorrhea. Surgery procedures lasted for 15-35 minutes (average 27.6 min). Rhinorrhea was stopped in all patients after the surgery, with no recurrence at a 10-month follow-up visit. In 1 case, the glue was expelled by coughing at 2 days after the surgery but was completely stopped with no recurrence after a second attempt. One patient with no recurrence at a 10-month follow-up died of tumor relapse at 12 months. In summary, fibrin glue could be used as a novel treatment for frontal sinus CSF rhinorrhea.
Assuntos
Rinorreia de Líquido Cefalorraquidiano/etiologia , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Seio Frontal/lesões , Fraturas Cranianas/complicações , Acidentes de Trânsito , Adulto , Rinorreia de Líquido Cefalorraquidiano/diagnóstico por imagem , Craniotomia , Feminino , Seio Frontal/diagnóstico por imagem , Seio Frontal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas Cranianas/diagnóstico por imagem , Fraturas Cranianas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Microglial activation and subsequent inflammatory responses are critical processes in aggravating secondary brain injury after intracerebral hemorrhage (ICH). Pterostilbene (3', 5'-dimethoxy-resveratrol) features antioxidant and anti-inflammation properties and has been proven neuroprotective. In this study, we aimed to explore whether Pterostilbene could attenuate neuroinflammation after experimental ICH, as well as underlying molecular mechanisms. Here, a collagenase-induced ICH in mice was followed by intraperitoneal injection of Pterostilbene (10 mg/kg) or vehicle once daily. PTE-treated mice performed significantly better than vehicle-treated controls in the neurological behavior test after ICH. Furthermore, our results showed that Pterostilbene reduced lesion volume and neural apoptosis, and alleviated blood-brain barrier (BBB) damage and brain edema. RNA sequencing and subsequent experiments showed that ICH-induced neuroinflammation and microglial proinflammatory activities were markedly suppressed by Pterostilbene treatment. With regard to the mechanisms, we identified that the anti-inflammatory effects of Pterostilbene relied on remodeling mitochondrial dynamics in microglia. Concretely, Pterostilbene reversed the downregulation of OPA1, promoted mitochondrial fusion, restored normal mitochondrial morphology, and reduced mitochondrial fragmentation and superoxide in microglia after OxyHb treatment. Moreover, conditionally deleting microglial OPA1 in mice largely countered the effects of Pterostilbene on alleviating microglial inflammation, BBB damage, brain edema and neurological impairment following ICH. In summary, we provided the first evidence that Pterostilbene is a promising agent for alleviating neuroinflammation and brain injury after ICH in mice, and uncovered a novel regulatory relationship between Pterostilbene and OPA1-mediated mitochondrial fusion.
Assuntos
Edema Encefálico , Lesões Encefálicas , Animais , Camundongos , Doenças Neuroinflamatórias , Microglia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Inflamação/tratamento farmacológico , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Hemorragia Cerebral/tratamento farmacológicoRESUMO
OBJECTIVE: Aneurysms occurring in the ophthalmic segment (C6) of the internal carotid artery (ICA) have complex anatomy. This poses a challenge for the use of traditional open surgery, which is gradually being replaced by endovascular treatment (EVT). However, multiple aneurysm (MA) EVT, especially in MAs occurring ipsilaterally, has not been specifically described or discussed. The present study aimed to propose a more concise clinical classification standard for ipsilateral C6 ICA MAs and report on the clinical experience with EVT. METHODS: The cases of 18 patients with ipsilateral C6 ICA MAs treated with EVT were retrospectively reviewed. The treatment results and procedure-related complications were recorded, and clinical and angiographic follow-ups were performed at least six months after surgery. RESULTS: A total of 38 ipsilateral C6 ICA aneurysms were treated during the study period and classified into four main types and six total subtypes based on anatomical features. There was a failure to coil through the stent in one aneurysm, while the remaining 37 were successfully treated using various EVT methods. Of these, 36 were completely concluded. One aneurysm had a size reduction, and one had no changes during the angiographic follow-up. All Tubridge flow diverter stents were patent. All patients achieved satisfactory clinical outcomes and were independent at the final follow-up. CONCLUSION: EVT may be safe and feasible for the treatment of C6 ICA MAs. Traditional stent-assisted coiling methods, the Willis covered stent, and the double-layered low-profile visualized intraluminal support stent all achieved favorable results. The flow diverter stent is also considered a safe and efficient option for selected aneurysms, but the visual deficit risk should be considered. The present study introduces a new EVT classification option based on the anatomical features of an aneurysm.
Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Artéria Carótida Interna/cirurgia , Estudos Retrospectivos , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Stents , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodosRESUMO
The ß3-adrenergic receptor (ADRB3), a G-protein coupled receptor, plays a major role in energy metabolism and regulation of lipolysis and homeostasis. We detect the single nucleotide polymorphism (SNP) variation in full-length sequence of ovine ADRB3 gene in 12 domestic sheep populations within four types by polymerase chain reaction-single strand conformation polymorphism and sequencing to reveal the breed difference. Twenty-two SNPs, 12 of which in the exon 1 and ten in the intron, were detected, and 12 new exonic and four new intronic SNPs were found. Most SNPs presented in Shanxi Dam Line and least ones in Dorset. The average SNP number in both meat and dual purpose for meat and wool breeds was significantly higher than general and dual purpose breeds for wool and meat. Frequency of each SNP in studied breeds or types was different. The 18C Del and 1617T Ins majorly existed in dual purpose breeds for wool and meat. The 25A Del, 119C>G and 130C>T were mostly found in the meat and dual purpose for meat and wool breeds. The 1764C>A more frequently presented in meat than in other types. The majority of variations came from within the populations as suggested by analysis of molecular variance. Close relationship presented among the Chinese and western breeds, respectively. In conclusion, SNPs of ovine ADRB3 gene can reflect the breed difference and within- and between-population variations, and to a great extent, the breed relationship.