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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.
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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.
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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 fármacosRESUMEN
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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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.
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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 SeguimientoRESUMEN
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.
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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.
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Nomogramas , Neuralgia del Trigémino , Humanos , Radiómica , Estudios Retrospectivos , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/cirugía , PronósticoRESUMEN
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.
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Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Humanos , Espasmo Hemifacial/cirugía , Resultado del Tratamiento , Nomogramas , Estudios Retrospectivos , Reproducibilidad de los ResultadosRESUMEN
Objective: To predict the volume and shape of the balloon before PBC by reconstructing the Meckel's cave (MC) and establishing a volumetric measurement model, supporting preoperative preparation and intraoperative decisions. Methods: The clinical data of 31 patients with good therapeutic effects who underwent PBC are retrospectively collected, including preoperative MRI, the volume of contrast agent injected into the balloon, and intraoperative lateral X-ray images. The MC on the affected side of the 31 patients is reconstructed based on MRI using 3D Slicer, while the volume of the MC is calculated to compare with the volume of contrast agent. The width (W) and length (L) of the model of the MC in lateral view are measured and used to classify the shape of the MC based on W/L. The consistency between the W/L of the model of the MC and the W/L of the intraoperative balloon is evaluated. Results: For volume, the mean value of the models of the MC (V1) in 31 patients is 399.77±155.13 mm³, while the mean value of the contrast agent injected during PBC (V2) is 539.03±111.93 mm³. The formula obtained by linear regression is V2= 392.1 + 0.3676×V1. Based on the value of W/L, the shape of the MC is classified into thin "pear" in 5 patients (16.13%), standard "pear" in 22 patients (70.97%), and square "pear" in 4 patients (12.90%). There is no significant difference in W/L between the models of the MC and the intraoperative balloons in 31 patients (P=0.221). Conclusion: In 31 patients with good efficacy, it is verified that the prediction of the MC before PBC by 3D Slicer is consistent with the actual situation of the intraoperative balloon. This method can provide certain basis for preoperative preparation and intraoperative judgment.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Cod (Gadus), a kind of herb from the Chinese herb. Traditionally, it has used to treat trauma, reduce swelling and relieve pain in order to exert its anti-inflammatory activity. Recent reports based on its hydrolyzed or enzymatic extracts have shown its anti-inflammatory, mucosal barrier protecting properties. However, its mechanism of improvement in ulcerative colitis is not clear. AIM OF THE STUDY: This study aimed to explore the preventive and protective effect of cod skin collagen peptide powder (CP) on mice with UC and to explore the underlying mechanism. MATERIALS AND METHODS: Mice with dextran sodium sulfate (DSS)-induced UC were treated with CP by gavage, and the anti-inflammatory effects of CP were assessed using general physical, pro-inflammatory cytokine, histopathological, immunohistochemical, macrophage flow cytometry, and inflammatory signaling pathway assays. RESULTS: CP ameliorates inflammation by upregulating mitogen-activated protein kinase phosphatase-1 (MKP-1) and thereby decreasing the phosphorylation levels of P38 and JNK. It also polarizes macrophages in the colon towards the M2 phenotype, which helps to reduce tissue damage and promotes colon repair. At the same time, CP also inhibits the development of fibrosis, one of the complications of UC, by upregulating ZO-1, Occludin, and downregulating α-SMA, Vimentin, Snail, and Slug. CONCLUSION: In this study, we found CP reduced inflammation in mice with UC by inducing MKP-1 expression, which caused dephosphorylation of mitogen-activated protein kinase (MAPK). CP also restored mucosal barrier function and inhibited the development of fibrosis complicating UC in these mice. Taken together, these results suggested that CP improved the pathological manifestations of UC in mice, suggesting that it can play a biological role as a nutritional supplement for preventing and treating UC.
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Colitis Ulcerosa , Colitis , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Dextranos , Polvos/uso terapéutico , Colitis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Colon , Antiinflamatorios/efectos adversos , Fibrosis , Sulfato de Dextran , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , FN-kappa B/metabolismoRESUMEN
Introduction: Despite verifying proton magnetic resonance spectroscopy (1H-MRS) for focal localization in magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE), it is necessary to illustrate metabolic changes and screen for effective biomarkers for monitoring therapeutic effect. We used 1H-MRS to investigate the role of metabolic levels in MRI-negative TLE. Materials and methods: Thirty-seven patients (n = 37, 14 women) and 20 healthy controls (n = 20, 11 women) were investigated by 1H-MRS. We compared the metabolite level changes in the epileptic and contralateral sides on the mesial temporal and dorsolateral prefrontal cortices and analyzed their association with clinical symptoms. Results: γ-Aminobutyric acid (GABA) levels were significantly lower on the epileptic side (2.292 ± 0.890) than in the contralateral side (2.662 ± 0.742, p = 0.029*) in patients on the mesial temporal lobe. N-acetylaspartate (NAA) levels were significantly lower on the epileptic side (7.284 ± 1.314) than on the contralateral side (7.655 ± 1.549, p = 0.034*). NAA + N-acetylaspartylglutamate levels were significantly lower on the epileptic side (7.668 ± 1.406) than on the contralateral side (8.086 ± 1.675, p = 0.032*). Glutamate levels were significantly lower on the epileptic side (7.773 ± 1.428) than on the contralateral side (8.245 ± 1.616, p = 0.040*). Moreover, a significant negative correlation was found between GABA levels in the epileptic mesial temporal lobe and tonic-clonic seizure frequency (r = -0.338, p = 0.046*). Conclusion: γ-Aminobutyric acid (GABA) is a potential biomarker for lateralization and monitoring seizure frequency in MRI-negative TLE.
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Background: Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients. Methods: Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours. Results: COX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion. Conclusion: Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.
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Glioma , Medicina de Precisión , Humanos , Pronóstico , Simulación del Acoplamiento Molecular , ADN Mitocondrial , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Mitocondrias/genéticaRESUMEN
BACKGROUND: Lymphovascular space invasion (LVSI) is a prognostic factor in the existing TNM classification system. The present meta-analysis assessed the role of LVSI in predicting the prognosis of stage IA to IIB cervical cancer (CC). MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library electronic databases were searched to determine relevant articles published in the English language. Our search deadline was May 2022. Critical Appraisal of Prognostic Studies was used to assess the quality for each article. Pooled hazard ratios (HRs) were used to evaluate the performance of LVSI in prognosis prediction. RESULTS: We enrolled 8 studies involving 25,352 patients published after 2010. Thus, high LVSI was an unfavorable factor in predicting overall survival (HR, 2.08; 95% confidence interval, 1.63-2.66; Pâ =â .006) and disease-free survival (HR, 2.20; 95% confidence interval, 1.79-2.70; Pâ =â .000) for patients with CC. However, the disease-free survival and overall survival were significantly different on univariate analysis based on the subgroup analysis stratified by analysis method, but no obvious heterogeneity was found across diverse articles. CONCLUSIONS: The present study showed that LVSI predicts the poor prognostic outcome of stage IA to IIB CC. However, well-designed clinical articles should further assess the independent prognosis prediction performance of LVSI in CC.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Pronóstico , Neoplasias del Cuello Uterino/patología , Supervivencia sin Enfermedad , Modelos de Riesgos Proporcionales , Estadificación de Neoplasias , Estudios Retrospectivos , Invasividad NeoplásicaRESUMEN
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.
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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 TratamientoRESUMEN
Glutamine (Gln) is an immunomodulatory protein that mediates oxidative stress, inflammation, and apoptosis, but has not been reported in the treatment of hyperoxia (Hyp)-induced brain injury. The aim of this study was to determine whether Gln could improve hyp-induced brain injury in neonatal rats to and later learning and memory dysfunction, and to explore its possible mechanisms. We prepared a model of neonatal rat brain injury caused by normobaric hyperoxia while administered with Gln for 7 days for evaluation. Learning memory function was assessed with the Morris water maze test. Histological analysis, protein expression analysis, oxidative stress and inflammation level analysis were performed using hippocampal tissue. Gln treatment significantly reduced brain tissue water content, oxidative stress levels, microglia activation and inflammatory factor expression, and attenuated tissue damage and apoptosis in the hippocampal region. Gln ameliorates hyp-induced learning, memory impairment in neonatal rats in water maze test. It also increased MKP-1 protein expression and decreased p-p38, p-ERK and p-JNK. Therefore, it is hypothesized that Gln may exert neuroprotective effects by increasing MKP-1 expression to negatively regulate MAPK signaling, with potential cognitive improvement in hyp-induced brain injury.
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Background: Parkinson's disease (PD) is a common, degenerative disease of the nervous system that is characterized by the death of dopaminergic neurons in the substantia nigra densa (SNpc). There is growing evidence that copper (Cu) is involved in myelin formation and is involved in cell death through modulation of synaptic activity as well as neurotrophic factor-induced excitotoxicity. Methods: This study aimed to explore potential cuproptosis-related genes (CRGs) and immune infiltration patterns in PD and the development of Cu chelators relevant for PD treatment. The PD datasets GSE7621, GSE20141, and GSE49036 were downloaded from the Gene Expression Omnibus (GEO) database. The consensus clustering method was used to classify the specimens of PD. Using weighted gene co-expression network analysis (WGCNA) and random forest (RF) tree model, support vector machine (SVM) learning model, extreme gradient boosting (XGBoost) model, and general linear model (GLM) algorithms to screen disease progression-related models, the column charts were created to verify the accuracy of these CRGs in predicting PD progression. Single sample genomic enrichment analysis (ssGSEA) was used to estimate the correlation between genes associated with copper poisoning and genes associated with immune cells and immune function. Molecular docking was used to verify interactions with copper chelating agents associated with cuproptosis for PD treatment. Results: Through ssGSEA, we identified three copper poisoning related genes ATP7A, NFE2L2 and MTF1, which are related to immune cells in PD. We also verified that LAGASCATRIOL can bind to NFE2L2 through molecular docking. Consistent cluster analysis identified two subtypes, among which C2 subtype was just enriched in PD. And to more accurately diagnose PD progression, patients can benefit from a feature map based on these genes. Conclusions: CRGs such as NFE2L2, MTF1, and ATP7B were identified to be associated with the pathogenesis of PD and provide a possible new direction for the treatment of PD, which needs further in-depth study.
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BACKGROUND: The role of the lymph node ratio (LNR) in the existing tumor node metastasis classification system should be verified as one of the prognosis prediction factors. This work evaluated LNR's performance in predicting cervical cancer (CC) prognosis through a meta-analysis. METHOD: Related studies were retrieved from the Cochrane Library, EMBASE, and PubMed databases. The language was restricted to English. The combined hazard ratios (HRs) were utilized to analyze the prognostic value of LNR. RESULTS: Our study included 8 articles with 3325 subjects published after 2015. Based on our analysis, high LNR was the adverse prognostic factor for overall survival (OS, HRâ =â 1.45; 95% CIâ =â 1.23-1.73; Pâ =â .238) and disease-free survival (DFS, HRâ =â 2.69; 95% CIâ =â 1.98-3.66; Pâ =â .597) among the CC cases. Furthermore, as revealed by subgroup analysis, in CC patients, median LNR of about 0.0625 and 0.066 served as the prominent risk factor for DFS and OS. CONCLUSIONS: The current work illustrates that elevated LNR is related to the dismal prognosis of CC. More well-designed clinical studies are warranted for assessing whether LNR is a factor independently predicting the prognosis of CC.
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Ganglios Linfáticos , Neoplasias del Cuello Uterino , Femenino , Humanos , Pronóstico , Metástasis Linfática/patología , Ganglios Linfáticos/patología , Índice Ganglionar , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Estudios Retrospectivos , Escisión del Ganglio LinfáticoRESUMEN
Atrial natriuretic peptide (ANP) plays a pivotal role in the regulation of the cardiovascular system. The ANP level increases during atrial fibrillation (AF), suggesting that AF may provoke ANP secretion, but its potential mechanism is still unclear. In the present study, the potential mechanisms of rapid atrial pacing (RAP) regulating ANP secretion was explored. Rabbits were subjected to burst RAP, ANP secretion increased whereas cyclic guanosine monophosphate (cGMP) concentrations decreased during RAP. The p-Akt and p-GSK-3ß levels decreased in atrial tissues. Natriuretic peptide receptor A (NPR-A) protein and particulate guanylate cyclase (PGC) activity were detected. The sensitivity of NPR-A to ANP decreased, leading to the decrease of PGC activity. Also, the isolated atrial perfusion system were made in the rabbit model, cGMP was shown to inhibit ANP secretion, and the Akt inhibitor LY294002 (LY) and GSK-3ß inhibitor SB216763 (SB) attenuated the inhibitory effects of cGMP on ANP secretion and enhanced the inhibitory effects of cGMP on atrial dynamics. In conclusion, NPR-A interacts with ANP to regulate PGC expression, and influence the expression of cGMP during RAP, which involves in the Akt/GSK-3ß signaling pathway. From the aforementioned points we conclude that cGMP regulates ANP secretion by the Akt/GSK-3ß signaling pathway during atrial pacing.
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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.
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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/farmacologíaRESUMEN
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.