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1.
Cancer Cell Int ; 24(1): 261, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049021

RESUMEN

BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a common malignant tumor of the urinary system, and its incidence is increasing. ERBB3 binding protein (EBP1) is upregulated in various cancers. However, the connection between EBP1 and KIRC has not been reported. METHODS: The expression of EBP1 in normal kidney tissue and KIRC tissue was analyzed through database and tissue microarray. EBP1 was knocked down in KIRC cell lines, and its impact on KIRC proliferation was assessed through CCK-8, soft agar assay, and flow cytometry. Scratch and transwell assays were used to evaluate the influence of EBP1 on KIRC invasion and migration. Nude mice tumor experiment were conducted to examine the effect of EBP1 on tumor tissue. Database analysis explored potential pathways involving EBP1, and validation was performed through Western blot experiments and p38 inhibitor. RESULTS: EBP1 is upregulated in KIRC and significantly correlates with clinical staging, pathological grading, and lymph node metastasis in patients. The mechanism research showed that knocking down EBP1 inhibited KIRC proliferation, invasion, and migration and inhibited p38 phosphorylation and the expression of hypoxia-inducible factor-1α (HIF-1α) in KIRC. p-38 inhibitor (SB203580) inhibits p38 phosphorylation and HIF-1α expression and suppresses cell viability in a concentration-dependent manner, but has no effect on EBP1 expression. HEK 293T cells overexpressing EBP1 showed increased expression of phosphorylated p38 and HIF-1α and enhanced cell viability, however, SB203580 inhibited this effect of EBP1. CONCLUSION: EBP1 may promote the occurrence and development of KIRC by regulating the expression of p38/HIF-1α signaling pathway.

2.
Neurosurg Rev ; 47(1): 109, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456944

RESUMEN

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.


Asunto(s)
Nomogramas , Neuralgia del Trigémino , Humanos , Radiómica , Estudios Retrospectivos , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/cirugía , Pronóstico
3.
Neurosurg Rev ; 47(1): 44, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38216699

RESUMEN

BACKGROUND: The course of disease after microvascular decompression (MVD) in patients with hemifacial spasm (HFS) is variable. The purpose of this study was to develop and validate a nomogram to predict the probability of delayed cure after microvascular decompression in patients with hemifacial spasms based on clinical multivariate factors. METHODS: A retrospective data collection was performed on 290 patients with HFS undergoing MVD at our center from January 2017 to January 2022. The patients were randomly assigned to the training cohort (n = 232) and validation cohort (n = 58) at a ratio of 8:2. Retrospective analysis was performed of information on clinical, radiological, and intraoperative findings and clinical outcomes. Univariate and multivariate analyses were performed in the training cohort, and a nomogram was constructed using a stepwise logistic regression approach. The receiver operating characteristic (ROC) was calculated to evaluate the reliability of the nomogram model. Decision curve analysis (DCA) was used to assess the clinical application value of the nomogram model. RESULTS: In the training cohorts, 73 patients (73/232) had a delayed cure. In the validation cohorts, 18 patients (18/58) had a delayed cure. We developed a novel nomogram model to predict the risk of delayed cure after MVD in HFS patients based on the presence of vertebral artery compression, venous compression, absence of LSR, degree of facial nerve indentation, degree of neurovascular compression, and internal auditory canal vascular looThe area under the curve (AUC) of the nomogram model was 0.9483 in the training cohort and 0.9382 in the validation cohort. The calibration curve showed good correspondence between the predicted and actual probabilities in the training and validation groups. The decision curve showed that the nomogram model had good performance in clinical applications. CONCLUSIONS: We developed and validated a preoperative and intraoperative multivariate factors nomogram to predict the possibility of delayed cure after MVD in HFS patients, which may help clinicians in the comprehensive management of HFS.


Asunto(s)
Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Humanos , Espasmo Hemifacial/cirugía , Resultado del Tratamiento , Nomogramas , Estudios Retrospectivos , Reproducibilidad de los Resultados
4.
BMC Surg ; 24(1): 154, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745320

RESUMEN

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.


Asunto(s)
Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Arteria Vertebral , Humanos , Espasmo Hemifacial/cirugía , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arteria Vertebral/cirugía , Adulto , Cirugía para Descompresión Microvascular/métodos , Resultado del Tratamiento , Anciano , Descompresión Quirúrgica/métodos , Estudios de Seguimiento
5.
BMC Pediatr ; 23(1): 142, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997989

RESUMEN

OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.


Asunto(s)
Epilepsia , Obesidad Infantil , Masculino , Femenino , Humanos , Niño , Lactante , Preescolar , Adolescente , Estudios Retrospectivos , Obesidad Infantil/complicaciones , Pérdida de Sangre Quirúrgica , Sobrepeso/complicaciones , Epilepsia/complicaciones , Epilepsia/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Índice de Masa Corporal , Resultado del Tratamiento
6.
Cancer Cell Int ; 22(1): 60, 2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35114996

RESUMEN

PURPOSE: Present work systematically reviewed relevant literature based on 18F-FDG PET parameters and conducted a meta-analysis to examine the prognostic value of maximal standard uptake value (SUVmax), total lesional glycolysis (TLG), and metabolic tumour volume (MTV) in the prognosis of malignant pleural mesothelioma (MPM). METHODS: The relevant literature published in English were searched on PubMed, Cochrane Library, and EMBASE databases. We also evaluated the significance of SUVmax, TLG, and MTV in prognosis prediction using pooled hazard ratios (HRs). RESULTS: The current study comprised 12 primary studies with a total of 1307 MPM cases. According to our results, the pooled HR (95% confidence interval [CI]) of increased SUVmax for overall survival (OS) was 1.30 (95% CI 1.13-1.49, P = 0.000), whereas the increased TLG was 1.81(95% CI 1.25-2.61, P = 0.089). The increased MTV was not significantly related to OS (1.14 [95% CI 0.87-1.50, P = 0.18]).However, study design-stratified subgroup analysis suggested that differences in OS of retrospective and prospective subgroups were statistically significant, and no significant heterogeneity among different studies was observed. CONCLUSION: Based on the findings from the present work, PET/CT can significantly affect the prognosis prediction in MPM cases. Also, the increased SUVmax and TLG values predict an increased risk of mortality.

7.
Exp Lung Res ; 48(4-6): 187-197, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35924334

RESUMEN

Background: Insulin-like growth factor-1 (IGF-1), a member of the insulin family, has a high degree of homology with insulin and exhibits anti-inflammatory and anti-oxidative stress properties. However, the potential protective effect of IGF-1 on hyperoxia-induced lung injury remains unknown. In this study, we aimed to explore the effects and mechanism of action of IGF-1 in hyperoxia-induced lung injury in neonatal rats. Materials and Methods: Hematoxylin-eosin staining was used to observe pathological changes in lung tissue; transmission electron microscopy was used to examine the ultrastructure, and ELISA was used to detect the level of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Further, malondialdehyde, glutathione, and superoxide dismutase activities in lung tissue were evaluated. TUNEL staining was used to detect cell apoptosis, and western blot analysis was used to detect the expression of Bax, Bcl-2, Caspase-3, p-PERK, p-eIF2α, ATF4, and CHOP in the lung tissue. Moreover, the wet/dry weight ratio of lung tissue was determined. Results: Intraperitoneal injection of IGF-1 effectively reduced lung tissue damage induced by hyperoxia; production of inflammatory cells and release of pro-inflammatory cytokines, oxidative stress, and cell apoptosis. Further, IGF-1 down-regulated the expression of ATF4, CHOP, and Bax/Bcl-2, and inhibited the phosphorylation of PERK and eIF2α. Conclusion: The results suggest that IGF-1 reduces hyperoxia-induced lung inflammation and oxidative stress in neonatal rats through the PERK/eIF2α/ATF4/CHOP signaling pathway and inhibits cell apoptosis.


Asunto(s)
Hiperoxia , Insulinas , Lesión Pulmonar , Neumonía , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/farmacología , Animales , Apoptosis , Citocinas/metabolismo , Estrés del Retículo Endoplásmico , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2 Eucariótico de Iniciación/farmacología , Hiperoxia/complicaciones , Hiperoxia/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Insulinas/metabolismo , Insulinas/farmacología , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Transducción de Señal , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción CHOP/farmacología , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/farmacología , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/farmacología
8.
Pharm Biol ; 60(1): 1732-1738, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36086879

RESUMEN

CONTEXT: Salidroside (SAL), one of the major glycosides isolated from the roots of Rhodiola rosea L. (Crassulaceae), has anti-inflammatory, antioxidant, and antidiabetic properties. OBJECTIVE: Our study assessed whether SAL exerts a protective effect on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via the Akt/GSK-3ß signalling pathway. MATERIALS AND METHODS: Adult male Wistar rats were divided into three groups (n = 8): normal control, DN + vehicle, and DN + SAL. SAL (50 mg/kg/day, oral) was administered for 8 weeks. Biochemical and histopathologic examinations were performed to evaluate the therapeutic effects of SAL on oxidative stress, inflammation, renal function, and apoptosis. RESULTS: SAL induced rats demonstrated ameliorated levels of FBG (20.53 ± 0.72 mmol/L vs. 26.02 ± 1.44 mmol/L), urine albumin excretion (27.00 ± 1.46 mmol/L vs. 41.00 ± 1.59 mmol/L), blood urea nitrogen (14.42 ± 0.70 mmol/L vs. 17.77 ± 0.72 mmol/L), and serum creatinine (112.80 ± 6.98 mmol/L vs. 159.00 ± 3.81 mmol/L) compared to normal control rats, along with the alleviation of renal pathologic changes by improving the irregular shape of glomeruli tissues. Biochemical analysis showed that SAL-treated animals displayed suppressed levels of serum inflammatory cytokines and kidney oxidative stress markers and attenuated apoptotic characteristics. Moreover, it increased the phosphorylation levels of Akt and GSK-3ß in kidneys. DISCUSSION AND CONCLUSION: The present study validated the involvement of the Akt/GSK-3ß signalling pathway in renal improvement. These findings can form the basis to investigate the protective effect of SAL in DN in clinical trials.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Animales , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/prevención & control , Glucósidos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Masculino , Estrés Oxidativo , Fenoles , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Estreptozocina/farmacología
9.
Mol Carcinog ; 60(4): 252-264, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33634940

RESUMEN

The ErbB3 binding protein 1 (Ebp1) has been reported in several cancers, in which it can act as either a pro-oncogenic regulator or a tumor suppressor. However, the biological function and molecular mechanism of Ebp1 p48 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that the long isoform of Ebp1, p48, is highly expressed in HCC tissues compared with normal tissues. Ebp1 p48 expression was correlated with the tumor size in HCC patients. Silencing Ebp1 p48 by transduction with lentiviral shEbp1 dramatically reduced the proliferation rate, soft agar colony generation, and tumor formation in vivo. We further demonstrated that Ebp1 p48 knockdown resulted in decreased p38 phosphorylation, which subsequently reduced hypoxia-inducible factor 1α (HIF1α) expression. Moreover, Ebp1 p48 knockdown led to an upregulation of p53 expression through MDM2 downregulation. Taken together, these results suggest that the Ebp1/p38/HIF1α signaling pathway and the Ebp1-mediated downregulation of p53 are involved in hepatocarcinogenesis. Therefore, Ebp1 and its downstream signaling pathways may be promising therapeutic targets of HCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Imidazoles/farmacología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Trasplante de Neoplasias , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Piridinas/farmacología , Análisis de Supervivencia , Análisis de Matrices Tisulares , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
10.
Cancer Cell Int ; 21(1): 293, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34090445

RESUMEN

BACKGROUND: The expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer. METHODS: The Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan-Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and ß-catenin activity was measured by a luciferase reporter system assay. RESULTS: Higher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of ß-catenin and its downstream targets, p-GSK-3ß and cyclin D1. CONCLUSION: FOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/ß-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.

11.
Korean J Physiol Pharmacol ; 25(3): 217-225, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33859062

RESUMEN

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

12.
Cancer Cell Int ; 20: 409, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32863768

RESUMEN

BACKGROUND: Diagnosis of metastatic castrate resistant prostate cancer (mCRPC) with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment. There are a number of prognostic biomarkers for CRPC, but there are no validated predictive biomarkers to guide in clinical decision-making. Specific biomarkers are needed that enable to understand the natural history and complex biology of this heterogeneous malignancy, identify early response to treatment outcomes and to identify the population of men most likely to benefit from the treatment. In this systematic review, we discuss the existing literature for the role of biomarkers in CRPC and how they aid in the prognosis, treatment selection and survival outcomes. METHODS: We performed a literature search on PubMed and EMBASE databases from January 2015 through February 2020 in accordance to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Articles were assessed to identify relevant observational studies and randomized controlled trials regarding biomarkers which aid in identifying progression to mCRPC as well as predictive biomarkers which help in treatment selection. RESULTS: We identified 3640 number of hits of which 58 articles were found to be relevant. Here we addressed biomarkers in the context of prognosis, prediction and patient selection of therapy. These biomarkers were found to be effective as prognostic or predictive factors under variety of conditions. The higher levels for all these biomarkers were associated with shorter median OS and sometimes PFS. Lower amounts of biomarkers in serum or urine were associated with prolonged survival outcomes, longer time to CRPC development or CRPC progression and longer median follow-up irrespective of any therapy. CONCLUSION: We observed that the biomarkers included in our study predicted clinically relevant survival outcomes and treatment exposure. Though the current biomarkers are prognostic when measured prior to initiating treatment, not all are validated as predictive markers in post treatment setting. A greater understanding of biomarkers in CRPC is need of the hour for development of more personalized approach to maximize benefit and minimize harm in men with CRPC.

13.
Exp Mol Pathol ; 112: 104333, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31705880

RESUMEN

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is closely linked to the occurrence and development of many malignant tumors. Many studies have reported that enhanced expression of LETM1 in several types of human cancers was associated with poor clinical outcomes; however, its clinical significance in gastric adenocarcinoma (GA) has not been elucidated. In this study, we assessed the expression of LETM1 along with the genes related to cancer stemness, cell cycle, and PI3K/Akt signaling in 189 paraffin-embedded GA tissue samples and GA-derived cell lines using immunohistochemistry (IHC), western blotting, and immunofluorescence. Our results showed that the expression of LETM1 was strongly correlated with the tumor grade, primary tumor (pT) stage, lymph node metastasis, clinical stage, and tumor gross type of GA. The Kaplan-Meier survival analysis revealed that patients with GA with high expression of LETM1 exhibit a shorter overall survival (OS) rate. Univariate and multivariate Cox regression analysis indicated that LETM1 is an independent poor prognostic factor of GA. Significantly, LETM1 expression was positively correlated with the expression of cancer stemness-related genes such as CD44 and LGR5 and expression of cell-cycle related gene, cyclin D1. Further, the expression of proteins involved in PI3K/Akt signaling pathway, such as pPI3K-p85 and pAkt-Thr308, was also increased. Additionally, small interfering RNA (esiRNA)-mediated silencing of LETM1 expression in GA-derived cell lines MKN28 and MKN74 strongly inhibited the expression of stemness and cell cycle-related proteins, suppressed cancer cell spheroid formation, migration and invasion ability, and affected cell cycle distribution. Furthermore, the GA-derived cell line AGS exhibited enhanced expression of LETM1, CD44, LGR5, and HIF1-α under hypoxic conditions. Lastly, we blocked PI3K expression using an inhibitor LY294002, which downregulated the expression of LETM1, pPI3K-p85, and pAkt-Thr308. Taken together, our results demonstrate that LETM1 regulates cell proliferation and promotes tumorigenicity of GA, and its overexpression is associated with the poor progression of GA. Therefore, LETM1 could serve as a potential prognostic biomarker and a therapeutic target for the better clinical management of GA.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Proteínas de Unión al Calcio/genética , Proteínas de la Membrana/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patología , Anciano , Proliferación Celular/genética , Ciclina D1/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Receptores de Hialuranos/genética , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteína Oncogénica v-akt/genética , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Neoplasias Gástricas/patología
14.
Surg Radiol Anat ; 42(4): 461-471, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31897654

RESUMEN

PURPOSE: The newborn umbilicus is provided by a fibrous ring after closure with a scar at the bottom. Since it is believed to be embedded in the linea alba, a specific connection with the rectus sheath was not yet hypothesized for the umbilicus. However, there are no or few descriptions about the development and growth. METHODS: We histologically examined 28 fetuses at 8-40 weeks: 6 fetuses at 8 weeks, 12 at 10-14 weeks and 10 at 31-40 weeks. RESULTS: An initial rectus sheath issued a linear mesenchymal condensation toward the umbilical cord at 10-14 weeks and, an established sheath provided a fibrous band around the umbilical cord at 31-40 weeks. The rectus sheath margins made an acute turn toward the skin at the superior and lateral rims of umbilicus and dispersed into a loose tissue of the cord. In contrast, the sheath margin changed its direction gradually to the superficial side at the inferior rim and inserted at a border between the skin epidermis and a mesothelium-like covering of the cord. The developing umbilical ring contained no or few elastic fibers. CONCLUSION: Instead of the underdeveloped linae alba, the rectus sheath seemed to be tightly connected with the umbilicus at birth. Rather than an expected elasticity, the rectus muscle contraction was likely to play a critical role in the closure after birth. Via the umbilical ring, the fetal rectus sheath also seemed to tightly connect with the skin at the inferior rim of umbilicus.


Asunto(s)
Desarrollo Fetal , Recto del Abdomen/embriología , Ombligo/embriología , Feto/anatomía & histología , Edad Gestacional , Humanos
15.
Korean J Physiol Pharmacol ; 24(3): 223-232, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32392913

RESUMEN

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

16.
Proc Natl Acad Sci U S A ; 112(31): E4288-97, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26187928

RESUMEN

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early-stage nonsmall cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here, we identify microRNA-224 (miR-224) to be significantly up-regulated in NSCLC tissues, particularly in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion, and proliferation by directly targeting the tumor suppressors TNFα-induced protein 1 (TNFAIP1) and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 functions as a potent oncogenic miRNA in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated miR-224, thus, facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 toward enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Regiones no Traducidas 3'/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Islas de CpG/genética , Metilación de ADN/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Sistema de Señalización de MAP Quinasas/genética , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Fenotipo , Regiones Promotoras Genéticas/genética , Proteínas/genética , Proteína Smad4/genética , Regulación hacia Arriba/genética
17.
Korean J Physiol Pharmacol ; 20(6): 613-619, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27847438

RESUMEN

Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-α and IL-1ß), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-3ß). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-3ß. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-3ß signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.

18.
Front Pharmacol ; 15: 1396023, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808258

RESUMEN

Salidroside (SAL), a phenylpropanoid bioactive compound, has various pharmacological properties, including antioxidant, anti-inflammatory, and hepatoprotective effects. However, the pharmacological effects and mechanisms of action of SAL on cholestatic liver injury are unclear. This study investigated the mechanism and effects of salidroside (SAL) on intestinal flora distribution and hepatic stellate cell (HSC) activation in cholestatic hepatic fibrosis. Bile duct ligation was used to cause cholestasis BALB/c mice. The therapeutic efficacy of SAL in liver fibrosis was assessed via serum/tissue biochemical analyses and liver tissue hematoxylin and eosin and Masson staining. Inflammation and oxidative stress were analyzed using enzyme-linked immunosorbent assay and western blotting. HSC were activated in vitro using lipopolysaccharide, and the effects of SAL on HSC migration and inflammatory factor expression were detected via scratch, transwell, and western blotting assays. The effects of SAL on the PI3K/AKT/GSK-3ß pathway in vivo and in vitro were detected using western blotting. 16sRNA sequencing was used to detect the effect of SAL on the diversity of the intestinal flora. Ileal histopathology and western blotting were used to detect the protective effect of SAL on the intestinal mucosal barrier. SAL reduces liver inflammation and oxidative stress and protects against liver fibrosis with cholestasis. It inhibits HSC activation and activates the PI3K/AKT/GSK-3ß pathway in vitro and in vivo. Additionally, SAL restores the abundance of intestinal flora, which contributes to the repair of the intestinal mucosal barrier, inhibits endotoxin translocation, and indirectly inhibits HSC activation, reversing the course of cholestatic liver fibrosis. SAL inhibits HSC activation through the PI3K/AKT/GSK-3ß pathway and improves intestinal flora distribution, thereby protecting and reversing the progression of hepatic fibrosis.

19.
J Ethnopharmacol ; 334: 118564, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38996946

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Alcoholic depression, a disorder of the central nervous system, is characterized by alcohol abuse, which causes blood-brain barrier disruption and oxidative damage in the brain. The rhizome of Rhodiola crenulate, from which Dazhu Hongjingtian Injection (DZHJTI) is derived, has been traditionally employed in ethnopharmacology to treat neurological disorders due to its neuroprotective, anti-inflammatory, and antioxidant properties. However, the exact mechanism by which DZHJTI alleviates alcoholic depression remains unclear. AIM OF THE STUDY: This study aimed to investigate the antidepressant effects of DZHJTI and its underlying mechanisms in a mouse model of alcohol-induced depression. MATERIALS AND METHODS: A model of alcoholic depression was established using C57BL/6J mice, and the effects of DZHJTI on depression-like behaviors induced by alcohol exposure were assessed through behavioral experiments. Histopathological examination was conducted to observe nerve cell damage and microglial activation in the hippocampal region. Oxidative stress indices in the hippocampus, inflammatory factors, and serum levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured using ELISA. Expression of proteins related to the Nrf2/HO-1/NLRP3 signaling pathway was determined by Western blot analysis. RESULTS: DZHJTI attenuated depression-like behaviors, neuronal cell damage, oxidative stress levels, inflammatory responses, and microglial activation. It also restored levels of brain-derived neurotrophic factor, brain myelin basic protein, DA, and 5-HT in mice with chronic alcohol exposure. After DZHJTI treatment, the expressions of Nuclear Respiratory Factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1) increased in the hippocampus, whereas the levels of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD, cleaved caspase-1, interleukin (IL)-1ß, and IL-18 decreased. CONCLUSIONS: DZHJTI ameliorates alcohol-induced depressive symptoms in mice through its antioxidant and anti-inflammatory effects, involving mechanisms associated with the Nrf2/HO-1/NLRP3 signaling pathway. This study highlights the potential of DZHJTI as a therapeutic option for alcohol-related depression and suggests the scope for future research to further elucidate its mechanisms and broader clinical applications.


Asunto(s)
Depresión , Medicamentos Herbarios Chinos , Etanol , Hemo-Oxigenasa 1 , Hipocampo , Factor 2 Relacionado con NF-E2 , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Transducción de Señal , Animales , Masculino , Ratones , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Depresión/inducido químicamente , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Hemo-Oxigenasa 1/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inflamación/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Rhodiola/química , Transducción de Señal/efectos de los fármacos
20.
Heliyon ; 10(9): e30000, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38694083

RESUMEN

Background: Trigeminal neuralgia (TN) secondary to a dural arteriovenous fistula (DAVF) is quite rare, and the goal of treatment is to resolve both the fistula and the pain. Case presentation: We herein report a case of TN secondary to a DAVF in a 64-year-old woman with a 1-year history of right-sided TN. Brain magnetic resonance imaging and digital subtraction angiography showed a right tentorial DAVF. Interventional embolization was performed, but the pain was not relieved after the operation. Six months later, we performed microvascular decompression of the trigeminal nerve. During the operation, we electrocoagulated the tortuous and dilated malformed vein, which was compressing the trigeminal nerve, to reduce its diameter and mitigate the compression on the cisternal segment of the trigeminal nerve. That patient's pain was relieved postoperatively. In addition, we reviewed the literature of TN caused by DAVF and found a total of 30 cases, 22 of which were treated by interventional embolization. Of these 22 cases, the interventional embolization healed the fistula with pain relief in 14 cases and healed the fistula without pain relief in 8 cases. We found that the venous drainage methods of the 8 cases were all classified into the posterior mesencephalic group. Conclusions: We believe that this drainage pattern contributes to the more common occurrence of unrelieved pain. For such patients, microvascular decompression can be performed with intraoperative coagulation to narrow the dilated veins until the cisternal segment of the trigeminal nerve is no longer compressed. Satisfactory curative effects can be obtained using this technique.

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