Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Toxicol Appl Pharmacol ; 472: 116570, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37268026

RESUMEN

Bone cancer pain is a difficult-to-treat pathologic condition that impairs the patient's quality of life. The effective therapy options for BCP are restricted due to the unknown pathophysiology. Transcriptome data were obtained from the Gene Expression Omnibus database and differentially expressed gene extraction was performed. DEGs integrated with pathological targets found 68 genes in the study. Butein was discovered as a possible medication for BCP after the 68 genes were submitted to the Connectivity Map 2.0 database for drug prediction. Moreover, butein has good drug-likeness properties. To collect the butein targets, we used the CTD, SEA, TargetNet, and Super-PRED databases. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed butein's pharmacological effects, indicating that butein may aid in treating BCP by altering the hypoxia-inducible factor, NF-kappa B, angiogenesis, and sphingolipid signaling pathways. Moreover, the pathological targets integrated with drug targets were obtained as the shared gene set A, which was analyzed by ClueGO and MCODE. Biological process analysis and MCODE algorithm further analyzed that BCP related targets were mainly involved in signal transduction process and ion channel-related pathways. Next, we integrated targets related to network topology parameters and targets of core pathways, identified PTGS2, EGFR, JUN, ESR1, TRPV1, AKT1 and VEGFA as butein regulated hub genes by molecular docking, which play a critical role in its analgesic effect. This study lays the scientific groundwork for elucidating the mechanism underlying butein's success in the treatment of BCP.


Asunto(s)
Neoplasias Óseas , Dolor en Cáncer , Medicamentos Herbarios Chinos , Osteosarcoma , Humanos , Farmacología en Red , Simulación del Acoplamiento Molecular , Calidad de Vida , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Biología Computacional
2.
Neurosurg Rev ; 46(1): 171, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37436536

RESUMEN

The systemic inflammatory response index (SIRI) is a well-known marker of systemic inflammation reflecting the body's inflammatory/immune state. The study aimed to evaluate the relationship between the SIRI on admission and aneurysmal subarachnoid hemorrhage (aSAH)-associated pneumonia and compare with other currently used bio-markers. We reviewed 562 successive patients with aneurysmal SAH who underwent endovascular treatment between January 2019 and September 2021. ASAH-associated pneumonia was diagnosed using the modified Centers for Disease Control and Prevention criteria. The SIRI on admission was calculated as monocyte count × neutrophil count / lymphocyte count. Multiple logistic regression models were used for data analysis. A total of 158 (28.11%) patients developed aSAH-associated pneumonia. Using the Multiple logistic regression analysis, a notable dose-response association was found between the elevated SIRI (fourth quartile) and aSAH-associated pneumonia (adjusted odds ratio = 6.759; 95% confidence interval [CI], 3.280-13.930; p < 0.001 [p for trend < 0.001]). The SIRI (0.701, 95% CI: 0.653-0.749) presented a higher area under the curve (AUC) than systemic immune- inflammation index (SII) (0.669, 95% CI: 0.620-0.718) (p = 0.089); neutrophil-to-lymphocyte ratio (NLR) (0.665, 95% CI: 0.616-0.714) (p = 0.035) and platelet-lymphocyte ratio (PLR) (0.587, 95% CI: 0.534-0.641) (p < 0.001). A higher SIRI on admission was associated with aSAH-associated pneumonia, which may guide further clinical trials of prophylactic antibiotic therapy.


Asunto(s)
Aneurisma , Neumonía , Hemorragia Subaracnoidea , Humanos , Biomarcadores , Hemorragia Subaracnoidea/complicaciones , Inflamación/complicaciones , Neumonía/complicaciones , Hospitales , Estudios Retrospectivos
3.
Neurosurg Rev ; 46(1): 142, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37338601

RESUMEN

Inflammation contributes to deep vein thrombosis (DVT) formation in patients with aSAH after endovascular treatment. The relationship between systemic immune-inflammatory index (SII) as an inflammatory marker and DVT formation remains unclear. Thus, this study aims to evaluate the association between SII and aSAH-associated DVT following endovascular treatment. We enrolled 562 consecutive patients with aSAH after endovascular treatment at three centers from January 2019 to September 2021. The endovascular treatments included simple coil embolization and stent-assisted coil embolization. Deep venous thrombosis (DVT) was assessed by Color Doppler ultrasonography (CDUS). Multivariate logistic regression analysis was used to establish the model. We assessed the association of the SII, neutrophil-to-lymphocyte ratio (NLR), the systemic inflammatory response index (SIRI), platelet-lymphocyte ratio (PLR), and DVT by using restricted cubic spline (RCS). ASAH-associated DVT was found in 136 (24.20%) patients. Based on the multiple logistic regression analysis, the correlation was found between aSAH-associated DVT and elevated SII (fourth quartile) (adjusted odds ratio = 8.20 [95% confidence interval, 3.76-17.92]; p < 0.001 [p for trend < 0.001]), elevated NLR (fourth quartile) (adjusted odds ratio = 6.94 [95% confidence interval, 3.24-14.89]; p < 0.001 [p for trend < 0.001]), elevated SIRI (fourth quartile) (adjusted odds ratio = 4.82 [95% confidence interval, 2.36-9.84]; p < 0.001 [p for trend < 0.001]), and elevated PLR (fourth quartile) (adjusted odds ratio = 5.49 [95% confidence interval, 2.61-11.57]; p < 0.001 [p for trend < 0.001]). The increased SII was correlated with the formation of aSAH-associated DVT after endovascular treatment.


Asunto(s)
Hemorragia Subaracnoidea , Trombosis de la Vena , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Inflamación/complicaciones , Linfocitos , Plaquetas , Trombosis de la Vena/complicaciones , Estudios Retrospectivos
4.
J Stroke Cerebrovasc Dis ; 32(4): 107052, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36780759

RESUMEN

BACKGROUND AND PURPOSE: Inflammation involves in the progression of intracranial aneurysms (IAs). However, whether the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker links to IAs stability is unidentified. This study was performed to assess the association of the NLR with IAs stability. METHODS: We retrospectively reviewed the medical records of patients diagnosed with unruptured IAs from January 2014 to June 2018. According to the quartiles of the NLR, patients with unruptured IAs were categorized into four groups. We evaluated the association between the NLR and IAs stability scores and IAs growth. Multiple logistic regression models were used in the analysis. RESULTS: A significant dose-response association was found between the NLR with IAs stability scores and IAs growth. After adjustment for potential confounders, an elevated NLR (fourth quartile) was associated with increased PHASES score (>5) (adjusted odds ratio [OR], 2.007; 95% confidence interval [CI], 1.361-2.960; p<0.001 [p for trend <0.001]), increased ELAPSS score (>15) (adjusted OR, 1.581; 95% CI, 1.074-2.328; p=0.020 [p for trend =0.001]), increased JAPAN 3-year rupture risk score (>5) (adjusted OR, 1.512; 95% CI, 1.033-2.215; p=0.034 [p for trend <0.001]), and IAs growth (adjusted OR, 16.759; 95% CI, 3.022-92.928; p=0.001 [p for trend <0.001]). CONCLUSION: An elevated NLR was associated with increased IAs stability scores and IAs growth. The association between NLR and IAs stability need further investigate.


Asunto(s)
Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Estudios Retrospectivos , Neutrófilos , Factores de Riesgo , Linfocitos
5.
Neurochem Res ; 47(7): 1791-1798, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35426597

RESUMEN

Gangliosides are important components of the neuronal cell membrane and play a vital role in the development of neurons and the brain. They participate in neurotransmission and are considered as the structural basis of learning and memory. Gangliosides participate in several and important physiological processes, such as cell differentiation, cell signaling, neuroprotection, nerve regeneration and apoptosis. The stability of ion concentration in excitable cells is particularly important in the maintenance of a steady state of cells and in the regulation of physiological functions. Ion concentration has been found to be related to the ganglioside's regulation in many neurological diseases, and several studies have found that they can stabilize intracellular ion concentration by regulating ion channels, which highlights their important regulatory role in neuronal excitability and synaptic transmission. Gangliosides can influence some forms of ion transport, by directly binding to ion transporters or through indirect binding and activation of transport proteins via appropriate signaling pathways. Therefore, the important and special role of gangliosides in the homeostasis of ion concentration is becoming a hot topic in the field and a theoretical basis in promoting help gangliosides use as key drugs for the treatment of nervous system diseases.


Asunto(s)
Gangliósidos , Enfermedades del Sistema Nervioso , Encéfalo/metabolismo , Gangliósidos/metabolismo , Humanos , Regeneración Nerviosa , Enfermedades del Sistema Nervioso/metabolismo , Neuronas/metabolismo , Transducción de Señal
6.
Neurochem Res ; 46(4): 755-769, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33389472

RESUMEN

Cerebral ischemia leads to reactive astrogliosis and glial scar formation. Glial scarring can impede functional restoration during the recovery phase of stroke. Salidroside has been shown to have neuroprotective effects after ischemic stroke, but its impact on long-term neurological recovery, especially whether it regulates reactive astrogliosis and glial scar formation, is unclear. In this study, male adult C57/BL6 mice were subjected to transient cerebral ischemia injury followed by intravenous salidroside treatment. Primary astrocytes were treated with lipopolysaccharide (LPS) or conditioned medium from cultured primary neurons subjected to oxygen-glucose deprivation (CM-OGD). Salidroside significantly improved long-term functional outcomes following ischemic stroke in the rotarod and corner tests. It also reduced brain glial scar volume and decreased expression of the glial scar marker, glial fibrillary acidic protein (GFAP) and inhibited astrocyte proliferation. In primary astrocyte cultures, salidroside protected astrocytes from CM-OGD injury-induced reactive astroglial proliferation, increasing the percentage of cells in G0/G1 phase and reducing the S populations. The inhibitory effect of salidroside on the cell cycle was related to downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA expression and increased p27Kip1 mRNA expression. Similar results were found in the LPS-stimulated injury model in astroglial cultures. Western blot analysis demonstrated that salidroside attenuated the CM-OGD-induced upregulation of phosphorylated Akt and glycogen synthase kinase 3ß (GSK-3ß). Taken together, these results suggested that salidroside can inhibit reactive astrocyte proliferation, ameliorate glial scar formation and improve long-term recovery, probably through its effects on the Akt/GSK-3ß pathway.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Gliosis/tratamiento farmacológico , Glucósidos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fenoles/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Astrocitos/efectos de los fármacos , Encéfalo/patología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Proliferación Celular/efectos de los fármacos , Gliosis/etiología , Gliosis/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo
7.
J Neuroinflammation ; 15(1): 39, 2018 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-29426336

RESUMEN

BACKGROUND: Following stroke, microglia can be driven to the "classically activated" pro-inflammatory (M1) phenotype and the "alternatively activated" anti-inflammatory (M2) phenotype. Salidroside (SLDS) is known to inhibit inflammation and to possess protective effects in neurological diseases, but to date, the exact mechanisms involved in these processes after stroke have yet to be elucidated. The purpose of this study was to determine the effects of SLDS on neuroprotection and microglial polarization after stroke. METHODS: Male adult C57/BL6 mice were subjected to focal transient cerebral ischemia followed by intravenous SLDS injection. The optimal dose was determined by evaluation of cerebral infarct volume and neurological functions. RT-PCR and immunostaining were performed to assess microglial polarization. A transwell system and a direct-contact coculture system were used to elucidate the effects of SLDS-induced microglial polarization on oligodendrocyte differentiation and neuronal survival. RESULTS: SLDS significantly reduced cerebral infarction and improved neurological function after cerebral ischemia. SLDS treatment reduced the expression of M1 microglia/macrophage markers and increased the expression of M2 microglia/macrophage markers after stroke and induced primary microglia from M1 phenotype to M2 phenotype. Furthermore, SLDS treatment enhanced microglial phagocytosis and suppressed microglial-derived inflammatory cytokine release. Cocultures of oligodendrocytes and SLDS-treated M1 microglia resulted in increased oligodendrocyte differentiation. Moreover, SLDS protected neurons against oxygen glucose deprivation by promoting microglial M2 polarization. CONCLUSIONS: These data demonstrate that SLDS protects against cerebral ischemia by modulating microglial polarization. An understanding of the mechanisms involved in SLDS-mediated microglial polarization may lead to new therapeutic opportunities after stroke.


Asunto(s)
Isquemia Encefálica/prevención & control , Polaridad Celular/efectos de los fármacos , Glucósidos/uso terapéutico , Microglía/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Fenoles/uso terapéutico , Animales , Isquemia Encefálica/patología , Polaridad Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Glucósidos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/fisiología , Neuroprotección/fisiología , Fenoles/farmacología , Ratas
8.
Stroke ; 47(2): 498-504, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26732561

RESUMEN

BACKGROUND AND PURPOSE: Interleukin-4 (IL-4) is a unique cytokine that may contribute to brain repair by regulating microglia/macrophage functions. Thus, we examined the effect of IL-4 on long-term recovery and microglia/macrophage polarization in 2 well-established stroke models. METHODS: Transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion was induced in wild-type and IL-4 knockout C57/BL6 mice. In a separate cohort of wild-type animals, IL-4 (60 ng/d for 7 days) or vehicle was infused into the cerebroventricle after transient middle cerebral artery occlusion. Behavioral outcomes were assessed by the Rotarod, corner, foot fault, and Morris water maze tests. Neuronal tissue loss was verified by 2 independent neuron markers. Markers of classically activated (M1) and alternatively activated (M2) microglia were assessed by real-time polymerase chain reaction, immunofluorescence, and flow cytometry. RESULTS: Loss of IL-4 exacerbated sensorimotor deficits and impaired cognitive functions ≤21 days post injury. In contrast to the delayed deterioration of neurological functions, IL-4 deficiency increased neuronal tissue loss only in the acute phase (5 days) after stroke and had no impact on neuronal tissue loss 14 or 21 days post injury. Loss of IL-4 promoted expression of M1 microglia/macrophage markers and impaired expression of M2 markers at 5 and 14 days post injury. Administration of IL-4 into the ischemic brain also enhanced long-term functional recovery. CONCLUSIONS: The cytokine IL-4 improves long-term neurological outcomes after stroke, perhaps through M2 phenotype induction in microglia/macrophages. These results are the first to suggest that immunomodulation with IL-4 is a promising approach to promote long-term functional recovery after stroke.


Asunto(s)
Isquemia Encefálica/inmunología , Interleucina-4/inmunología , Macrófagos/inmunología , Microglía/inmunología , ARN Mensajero/metabolismo , Receptores de Superficie Celular/inmunología , Daño por Reperfusión/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/genética , Infusiones Intraventriculares , Interleucina-4/genética , Interleucina-4/farmacología , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/efectos de los fármacos , Pruebas Neuropsicológicas , Receptores de Superficie Celular/genética , Daño por Reperfusión/genética
9.
Tumour Biol ; 37(5): 6323-30, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26628298

RESUMEN

Inhibitor of apoptosis-stimulating protein of p53 (iASPP), encoded by PPP1R13L gene, is often overexpressed in human cancers. From the PPP1R13L gene, at least two isoforms, iASPP-L and iASPP-SV, are produced through alternative splicing. However, the role of these isoforms in glioma is still elusive. In this study, we examined the expression of iASPP-SV in astrocytic glioma tissues with different grades and normal human cerebral tissues. The result showed a higher messenger RNA (mRNA) expression level of iASPP-SV in astrocytic glioma patients with World Health Organization (WHO) grade II to IV in comparison to the normal controls. Additionally, mRNA expression level of iASPP-SV was gradually increased with the raise of the grade in glioma. High mRNA expression level of iASPP-SV was significantly associated with malignant WHO grades (P < 0.001). The protein expression level of iASPP-SV was consistent with the mRNA expression level. The Kaplan-Meier analysis revealed that high iASPP-SV mRNA expression significantly affected overall survival and progression-free survival (both P < 0.001). Furthermore, multivariate analysis indicated that the mRNA expression of iASPP-SV was an independent prognostic marker in glioma (P < 0.001). To further explore the role of iASPP-SV in glioma, U87 cells were transfected with iASPP-SV by lentivirus and then treated with temozolomide (TMZ). Overexpression of iASPP-SV promoted the cell viability and downregulated the expression of pro-apoptosis genes (Bax, Puma, p21, and Noxa) to inhibit apoptosis induced by TMZ. Our study provides the first evidence that high iASPP-SV expression may be a novel prognostic factor and therapeutic target for glioma.


Asunto(s)
Glioma/tratamiento farmacológico , Glioma/genética , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Pronóstico , Proteínas Represoras/biosíntesis , Adulto , Anciano , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/patología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas Represoras/genética , Temozolomida
10.
Zhonghua Yi Xue Za Zhi ; 95(39): 3217-9, 2015 Oct 20.
Artículo en Zh | MEDLINE | ID: mdl-26814122

RESUMEN

OBJECTIVE: To investigate the relevant factors affecting the prognosis of traumatic optic neuropathy (TON). METHODS: A total of 685 cases (719 eyes) of TON from June 2007 to June 2012 were analyzed retrospectively. A total of 9 independent variables (X) including sex, side of TON, duration of coma, vision after trauma, fracture of optic nerve canal, fracture of big ridge of sphenoid bone, hematoma in sphenoid sinus and surgical treatment, and the dependent variable (Y) of visual prognosis were analyzed using the unconditioned Logistic regression analysis to find the risk factors for the visual prognosis of TON. RESULTS: A total of 325 eyes (45.2%) recovered out of 719 eyes. Four variables showed a significant relation with the visual recovery: duration of coma>0.5 h (X3, P<0.01), remnant vision after trauma (X4, P<0.01) and sphenoid ridge fractures (X7, P<0.01), and surgical treatment (X9, P<0.01). These factors above were also proved to be significant in Logistic regression. CONCLUSION: The duration of coma>0.5 h, no light perception after trauma, sphenoid ridge fractures are risk factors of visual recovery, while surgical treatment is the protective factor for the visual recovery after TON.


Asunto(s)
Enfermedades del Nervio Óptico , Visión Ocular , Fracturas Óseas , Hematoma , Humanos , Modelos Logísticos , Traumatismos del Nervio Óptico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
11.
World Neurosurg ; 181: e1130-e1137, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37995993

RESUMEN

OBJECTIVE: This study presents the clinical characteristics, imaging manifestations, and surgical experience in 38 patients diagnosed with craniofacial fibrous dysplasia in fronto-orbital region (foFD). METHODS: We retrospectively analyzed the clinical data from 38 patients who had surgery for foFD. The surgical procedure typically involved extensive tumor removal, followed by immediate reconstruction of the frontal bone and orbit using synthetic materials. Additionally, 9 patients underwent simultaneous microscopic decompression of the optic canal. RESULTS: Common clinical manifestations included progressive fronto-orbital bone deformity (35), proptosis (28), orbital dystopia (21), and visual impairment (9). The disease primarily affecting the frontal bone (38), the sphenoid bone (28), and the ethmoid bone (24). The optic canal was involved in 9 patients with functional impairment. Computed tomography scans in all 38 cases revealed satisfactory repair material positioning and complete resolution of frontal deformities. Among the 9 patients who underwent optic canal decompression, 7 experienced partial recovery of visual acuity after surgery. CONCLUSIONS: In the surgical treatment of foFD, it is crucial to achieve maximal bone resection and repair skull defects, while decompressing the optic canal can provide significant benefits for patients with decreased visual function preoperatively. The use of preformed artificial materials offers advantages in aesthetic restoration after lesion excision.


Asunto(s)
Displasia Fibrosa Craneofacial , Displasia Fibrosa Ósea , Enfermedades Orbitales , Humanos , Estudios Retrospectivos , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Ósea/cirugía , Órbita/diagnóstico por imagen , Órbita/cirugía , Enfermedades Orbitales/cirugía , Tomografía Computarizada por Rayos X
12.
Stroke ; 44(7): 1973-80, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23696548

RESUMEN

BACKGROUND AND PURPOSE: p53-mediated neuronal death is a central pathway of stroke pathophysiology, but its mechanistic details remain unclear. Here, we identified a novel microRNA mechanism that downregulation of inhibitory member of the apoptosis-stimulating proteins of p53 family (iASPP) by the brain-specific microRNA-124 (miR-124) promotes neuronal death after cerebral ischemia. METHODS: In a mouse model of focal permanent cerebral ischemia, the expression of iASPP and miR-124 was quantified by reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence staining, and Western blot. Luciferase reporter assay was used to validate whether miR-124 can directly bind to the 3'-untranslated region of iASPP mRNA. To evaluate the role of miR-124, miR-124 mimic and its inhibitor were transfected into Neuro-2a cells and C57 mice. RESULTS: There was no change in the iASPP mRNA level in cerebral ischemia. However, iASPP protein was remarkably decreased, with a concurrent elevation in miR-124 level. Furthermore, miR-124 can bind to the 3'-untranslated region of iASPP in 293T cells and downregulate its protein levels in Neuro-2a cells. In vivo, infusion of miR-124 decreased brain levels of iASPP, whereas inhibition of miR-124 enhanced iASPP levels and significantly reduced infarction in mouse focal cerebral ischemia. CONCLUSIONS: These data demonstrate that p53-mediated neuronal cell death after stroke can be nontranscriptionally regulated by a novel mechanism involving suppression of endogenous cell death inhibitors by miR-124. Further dissection of microRNA regulatory mechanisms may lead to new therapeutic opportunities for preventing neuronal death after stroke.


Asunto(s)
Isquemia Encefálica/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , MicroARNs/fisiología , Proteínas Represoras/metabolismo , Accidente Cerebrovascular/metabolismo , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo/fisiología , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria
13.
J Ethnopharmacol ; 311: 116448, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37030557

RESUMEN

ETHNOPHARMACOLOGY RELEVANCE: Tripterygium wilfordii Hook. f. has been widely used in clinical practice due to its good anti-inflammatory and analgesic activities. However, its application is limited by potential toxicity and side effects. AIM OF THE STUDY: The study aimed to identify the mechanisms responsible for the pharmacological activity and cardiotoxicity of the main monomers of Tripterygium wilfordii. MATERIALS AND METHODS: Database analysis predicted that ion channels may be potential targets of Tripterygium wilfordii. The regulatory effects of monomers (triptolide, celastrol, demethylzeylasteral, and wilforgine) on protein Nav1.5 and Nav1.7 were predicted and detected by Autodock and patch clamping. Then, we used the formalin-induced pain model and evaluated heart rate and myocardial zymograms to investigate the analgesic activity and cardiotoxicity of each monomer in vivo. RESULTS: All four monomers were able to bind to Nav1.7 and Nav1.5 with different binding energies and subsequently inhibited the peak currents of both Nav1.7 and Nav1.5. The monomers all exhibited analgesic effects on formalin-induced pain; therefore, we hypothesized that Nav1.7 is one of the key analgesic targets. Demethylzeylasteral reduced heart rate and increased the level of creatine kinase-MB, thus suggesting a potential cardiac risk; data suggested that the inhibitory effect on Nav1.5 might be an important factor underlying its cardiotoxicity. CONCLUSION: Our findings provide an important theoretical basis for the further screening of active monomers with higher levels of activity and lower levels of toxicity.


Asunto(s)
Triterpenos , Canales de Sodio Activados por Voltaje , Tripterygium , Cardiotoxicidad
14.
Trials ; 24(1): 207, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36941714

RESUMEN

BACKGROUND: Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5-33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. METHODS: This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18-90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. DISCUSSION: This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.


Asunto(s)
Hematoma Subdural Crónico , Humanos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Prospectivos , Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/cirugía , Recurrencia , Drenaje/efectos adversos , Drenaje/métodos , Resultado del Tratamiento , Craneotomía/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
15.
Int J Biol Macromol ; 216: 537-546, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35809671

RESUMEN

Corydalis yanhusuo W. T. Wang, a traditional Chinese herbal medicine, has been used as an analgesic for thousands of years and it also promotes blood circulation. In this study, 33 Corydalis yanhusuo alkaloid active components were acquired from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). A total of 543 pain-related targets, 1774 arrhythmia targets, and 642 potential targets of these active components were obtained using Swiss Target Prediction, GeneCards, Open Target Platform, and Therapeutic Target Database. Fifty intersecting targets were visualized through a Venn diagram, KEGG and GO pathway enrichment analysis. The analysis proposed that sodium ion channels are likely potential targets of Corydalis yanhusuo active components as analgesia and anti-arrhythmia agents. Molecular docking showed that the 33 components could bind to Nav1.7 and Nav1.5 (two subtypes of ion channel proteins) with different binding energies. In a patch clamp study, dihydrosanguinarine and dihydrochelerythrine, two monomers with the strongest binding effects, could inhibit the peak currents and promote both activation and inactivation phases of Nav1.5. Meanwhile, dihydrosanguinarine and dihydrochelerythrine could also inhibit peak currents and promote the activation phase of Nav1.7. Therefore, the findings from this study provide valuable information for future uses of traditional Chinese medicines to treat pain and cardiovascular disease.


Asunto(s)
Corydalis , Medicamentos Herbarios Chinos , Canales de Sodio Activados por Voltaje , Analgésicos/farmacología , Analgésicos/uso terapéutico , Antiarrítmicos , Corydalis/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento Molecular , Dolor , Extractos Vegetales/química
16.
J Ethnopharmacol ; 297: 115567, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-35870684

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a chronic liver disease that can lead to cirrhosis, liver failure, and hepatocellular carcinoma, and it is associated with long-term adverse outcomes and mortality. As a primary resource for complementary and alternative medicine, traditional Chinese medicine (TCM) has accumulated a large number of effective formulas for the treatment of liver fibrosis in clinical practice. However, studies on how to systematically optimize TCM formulas are still lacking. AIM OF THE REVIEW: To provide a methodological reference for the systematic optimization of TCM formulae against liver fibrosis and explored the underlying molecular mechanisms; To provide an efficient method for searching for lead compounds from natural sources and developing from herbal medicines; To enable clinicians and patients to make more reasonable choices and promote the effective treatment toward those patients with liver fibrosis. MATERIALS AND METHODS: TCM formulas related to treating liver fibrosis were collected from the Web of Science, PubMed, the China National Knowledge Infrastructure (CNKI), Wan Fang, and the Chinese Scientific Journals Database (VIP). Furthermore, the TCM compatibility patterns were mined using association analysis. The core TCM combinations were found by designing an optimized formulas algorithm. Finally, the hub target proteins, potential molecular mechanisms, and active compounds were explored through integrative pharmacology and docking-based inverse virtual screening (IVS) approaches. RESULTS: We found that the herbs for reinforcing deficiency, activating blood, removing blood stasis, and clearing heat were the basis of TCM formulae patterns. Furthermore, the combination of Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge; Chinese salvia/Danshen), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge; Astragalus/Huangqi), and Radix Bupleuri (Bupleurum chinense DC.; Bupleurum/Chaihu) was identified as core groups. A total of six targets (TNF, STAT3, EGFR, IL2, ICAM1, PTGS2) play a pivotal role in TCM-mediated liver fibrosis inhibition. (-)-Cryptotanshinone, Tanshinaldehyde, Ononin, Thymol, Daidzein, and Formononetin were identified as active compounds in TCM. And mechanistically, TCM could affect the development of liver fibrosis by regulating inflammation, immunity, angiogenesis, antioxidants, and involvement in TNF, MicroRNAs, Jak-STAT, NF-kappa B, and C-type lectin receptors (CLRs) signaling pathways. Molecular docking results showed that key components had good potential to bind to the target genes. CONCLUSION: In summary, this study provides a methodological reference for the systematic optimization of TCM formulae and exploration of underlying molecular mechanisms.


Asunto(s)
Medicamentos Herbarios Chinos , Plantas Medicinales , Salvia miltiorrhiza , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Medicina Tradicional China/métodos , Simulación del Acoplamiento Molecular
17.
Ann Transl Med ; 10(10): 542, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35722373

RESUMEN

Background: The choice and efficacy of surgical or/and surgical treatments for traumatic optic neuropathy (TON) remained controversial by now. This study aims to present the outcomes of surgical and nonsurgical treatments for TON in our center. Methods: A total of 685 consecutive patients were retrospectively included in the study. And divided into surgical and non-surgical groups. All cases were treated with corticosteroids for 3 days after admission. Endoscopic optic decompression was applied to 479 patients of surgical group; The other 206 patients of nonsurgical were administered with corticosteroids alone. The visual outcomes before and after treatment were compared with Wilcoxon rank and tests. The improvement rate between two groups were compared with chi-square test. Results: The visual acuity (VA) after treatment was significantly better than that before treatment (P=0.000). Overall VA improvement rate in the surgical group was better than that in non-surgical group (42.8% vs. 35.4%) with no significant difference (P=0.072). The VA improvement rate was significant greater in the surgical group than that in the non-surgical group in the patients with NLP before treatment (P=0.028). The VA improvement rate was better in the surgical group than that in the non-surgical group (71.9% vs. 57.8%) but with no significant difference. The final overall VA was 0.1 or better in 43 cases; 104 cases were able to count fingers; hand motion (HM) became perceivable in 132 cases; light perception (LP) was achieved in 53 cases; and no light perception (NLP) remained in 353 cases. Conclusions: Endoscopic optic nerve decompression (EOND) combined with corticosteroids or corticosteroids alone could reach the improvement for patients with TON. The EOND combined with corticosteroids could achieve better VA improvement in patients with NLP.

18.
Gland Surg ; 10(12): 3314-3323, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35070891

RESUMEN

BACKGROUND: As one of the most common intracranial tumors, pituitary adenomas, especially the Cushing's disease subtype, have been studied for many years. However, at present, effective methods for the early diagnosis of pituitary adenomas are very limited, especially for subtypes such as Cushing's disease. Therefore, it is of urgent importance to find effective molecular targets to develop new diagnostic and therapeutic methods for pituitary adenomas. METHODS: We showed the abnormally high expression of miR-30d in pituitary adenomas by analyzing data in the Gene Expression Omnibus (GEO) database and revealed a novel molecular mechanism of miR-30d in regulating the proliferation and invasion of a pituitary adenoma cell line (AtT-20). Cell culture and transfection, and RNA interference (RNAi) were used to treat AtT-20 cells to test the effects of miR-30d and TIMP3 on cells. Quantitative polymerase chain reaction (qPCR) was used to determine the messenger RNA (mRNA) expressions. We used 3-(4,5-diphenyltetrazolium bromide) (MTT) to determine cell viabilities. An invasion assay was performed using Transwell chambers. Luciferase activity was tested with a dual-luciferase assay. RESULTS: We found that the expression of miR-30d in pituitary adenoma was higher than that in normal pituitary tissues. It was revealed that miR-30d promoted the proliferation and invasion of AtT-20 cells by inhibiting the expression of TIMP3. In the above process, miR-30d could bind to the 3'-untranslated region (3'-UTR) of TIMP3 mRNA. CONCLUSIONS: The mir-30d/TIMP3 signaling pathway plays an important regulatory role in pituitary adenomas. These new discoveries may reveal more functions of miR-30d and lay the foundation for future clinical development of new drug targets.

19.
Ann Transl Med ; 9(2): 168, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33569470

RESUMEN

BACKGROUND: This study aimed to explore the molecular mechanism of mild hypothermia in in the treatment of cerebral ischemia, microRNA (miRNA) microarrays and bioinformatics analysis were employed to examine the miRNA expression profiles of rats with mild therapeutic hypothermia after middle cerebral artery occlusion (MCAO). METHODS: MCAO was induced in Male Sprague-Dawley rats. Mild hypothermia treatment began from the onset of ischemia and maintained for 3 hours. miRNA expressions following focal cerebral ischemia and mild hypothermia treatment were profiled using microarray technology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functions of the target genes in mild therapeutic hypothermia after MCAO. 60 min before MCAO, mimics and inhibitor of miR-291b were injected into the right lateral ventricle respectively, then the infarct volume and neuronal apoptosis were analyzed. RESULTS: Six upregulated miRNAs and 6 downregulated miRNAs were detected 4 hours after mild therapeutic hypothermia, and after 24 hours, 41 and 10 miRNAs were upregulated and downregulated, respectively. The target genes of the differentially expressed genes were mainly related with multicellular organism development and the mucin type O-glycan biosynthesis pathway was the most enriched KEGG pathway. Among the differentially expressed miRNAs, miR-291b was selected to assess the effects of mild therapeutic hypothermia in MCAO rats. At 24 hours after mild therapeutic hypothermia, miR-291b overexpression was proved to exhibit neuroprotective effects. CONCLUSIONS: The results showed that miRNAs might play a pivotal role in mild therapeutic hypothermia in cerebral ischemia/reperfusion injury. Further understanding of the mechanism and function of miRNAs would help to illuminate the mechanism of mild therapeutic hypothermia in cerebral ischemia/reperfusion injury.

20.
Ann Transl Med ; 9(2): 136, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33569438

RESUMEN

BACKGROUND: The aim of the present study was to discuss the efficacy of delayed wider endoscopic optic decompression in traumatic optic neuropathy (TON). METHODS: A total of 479 patients were treated with corticosteroids and delayed wider endoscopic optic decompression, including the injury-to-surgery interval, within 2 weeks in patients with no light perception (NLP), and within 1 month in patients with residual eyesight. Based on the traditional decompression range, the superior wall of the optic canal was further decompressed. The preoperative and postoperative visual acuities (VAs) were reviewed, and the therapeutic efficacy was analyzed. RESULTS: The final VA was 0.1 or better in 29 cases, finger count in 79 cases, hand motion in 99 cases, light perception (LP) in 25 cases, and NLP in 247 cases. A total of 136 patients (136/383, 35.5%) recovered after NLP treatment, and 78 patients (69/96, 71.9%) had improved residual eyesight. The improvement rate in patients with residual eyesight was significantly higher than that of patients with NLP (P<0.01). Moreover, the total VA after treatment was better than that before surgery (P<0.01). CONCLUSIONS: Delayed wider optic nerve decompression plus corticosteroids remains an effective and safe therapeutic strategy for patients with delayed treatment intervals of more than 1 week, especially for those with residual eyesight within 1 month.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA