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BACKGROUND: Pulmonary sequestration (PS) is a rare congenital lower airway malformation. This study presents the clinical and imaging features and surgical outcomes of PS in adults, and compare the safety and feasibility of minimally invasive surgery versus open thoracotomy for PS. METHODS: Adult patients with PS treated at our center from July 2011 to September 2021 were included. Information regarding the patient demographics, clinical and CT features, arterial supply and venous drainage, and surgical outcomes were collected. RESULTS: Ninety seven patients were included. The most common CT findings were mass lesions (50.5%) and cystic lesions (20.6%). The vast majority of the lesions (96 out of 97) were located close to the spine in the lower lobes (left vs. right: 3.6 vs. 1). Arterial supply was mainly provided by the thoracic aorta (87.4%) and abdominal aorta (10.5%). Intralobar and extralobar PS accounted for 90.7% and 9.3% of the patients, respectively. Three (4.5%) patients who underwent minimally invasive surgery were converted to open thoracotomy due to dense adhesions. Though no significant differences regarding operative time (P = 0.133), the minimally invasive surgery group was significantly better than the open thoracotomy group regarding intraoperative blood loss (P = 0.001), drainage volume (P = 0.004), postoperative hospital days (P = 0.017) and duration of chest drainage (P = 0.001). There were no cases of perioperative mortality. Only four (4.1%) patients developed postoperative complications, and no significant difference existed between the two groups. CONCLUSION: Our study revealed PS can present with a variety of different clinical and radiologic manifestations. Clinicians should consider the possibility of PS when diagnosing a lesion in the lower lobes close to the spine. Moreover, minimally invasive surgery is a safe and effective treatment modality for the treatment of PS in an experienced center.
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Secuestro Broncopulmonar , Humanos , Adulto , Secuestro Broncopulmonar/diagnóstico por imagen , Secuestro Broncopulmonar/cirugía , Secuestro Broncopulmonar/complicaciones , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Pulmón/patología , Resultado del TratamientoRESUMEN
BACKGROUND: We characterized the clinical features, radiographic characteristics, and response to treatment of immunocompetent and immunocompromised patients with pulmonary cryptococcosis (PC). METHODS: We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection between May 2015 and November 2020 in a tertiary referral center. RESULTS: A total of 21 males and 18 females were included in the study. 23 patients were immunocompetent and 20 out of the 39 were asymptomatic. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). Single nodule pattern was the most frequent lesion pattern (33 out of 39, 84.6%) and right upper lobe was the most common site of location (15 out of 47, 31.9%). The majority of lesions were located peripherally (38 out of 47, 80.9%) and most lesions were 1-2 cm in diameter (30 out of 47, 63.8%). Cavitation was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04) and there was complete resolution of PC in all patients treated with anti-fungal therapy. CONCLUSIONS: Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients. Single nodule pattern was the most frequent lesion pattern in PC patients. Cavitation was more likely to occur in immunocompromised patients than in immunocompetent patients.
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Criptococosis/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico , Adulto , Criptococosis/diagnóstico por imagen , Criptococosis/tratamiento farmacológico , Femenino , Humanos , Inmunocompetencia , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Radiografía , Estudios RetrospectivosRESUMEN
BACKGROUND: Blend sign on initial computed tomography (CT) is associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the mechanisms underlying the blend sign formation are poorly understood. The present study aimed to explore the possible mechanism of the CT blend sign in patients with ICH. METHODS: Seventy healthy rabbits were selected to prepare an ICH model. The animals were assigned to a whole blood group + whole blood group (ww group, 50 rabbits), a whole blood + plasma group (wp group, 10 rabbits) or a whole blood + serum group (ws group, 10 rabbits). The animals of the ww group were allocated to five subgroups based on the interval between the first infusion of blood and the second one. The subgroups included ww 1 h group (with an interval of 1 h), ww 2 h group, ww 3 h group, ww 4 h group and ww 5 h group. The rabbits from each group received first infusion of 0.3 mL of whole blood into the basal ganglia area to form a hematoma. Then, they received a second infusion of the same amount of whole blood, plasma or serum into the brain to form another hematoma adjacent to the first one. RESULTS: A hematoma with two densities on brain CT could be formed in each group after a second infusion of blood into the brain. A significant difference in CT attenuation values was observed between the hyperattenuation and the hypoattenuation in all the groups. However, only the morphological features of the hematoma in the ww group was in accordance with the CT blend sign observed in humans. The CT attenuation values in the hypodensity area of the ww 4 h group or the ww 5 h group were decreased compared with the ww 1 h group to the ww 3 h group. CONCLUSIONS: The CT blend sign observed in humans might be composed of two parts of blood with different ages. The hypodense area might be blood with older age and the hyperdense area might be new bleeding.
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Hemorragia Cerebral , Hematoma , Anciano , Animales , Ganglios Basales , Hemorragia Cerebral/diagnóstico por imagen , Humanos , Neuroimagen , Conejos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To study the molecular mechanisms of miR-18a aggravating intracranial hemorrhage (ICH) by increasing the blood-brain barrier (BBB) permeability. METHODS: Brain microvascular endothelial cells (BMVECs) and astrocytes were isolated, identified, and co-cultured to establish in vitro BBB model. BMVECs co-cultured with astrocytes were stimulated with or without thrombase and then transfected with miR-18a mimic and/or si-RUNX1. The trans-endothelial electric resistance (TEER) and FlNa flux were measured, respectively. The potential interaction between RUNX1 and miR-18a was also detected. Additionally, SD rats were injected with fresh autologous non-anticoagulant blood into the brain basal ganglia to establish ICH model. After administration with miR-18a, sh-miR-18a, miR-18a+RUNX1, sh-miR-18a+sh-RUNX1, respectively, BBB permeability was assessed. RESULTS: After overexpressing miR-18a, the expression levels of RUNX1, Occludin and ZO-1 were decreased, but the Evan's blue contents and brain water contents were significantly increased in ICH rats. Additionally, rat neurological function was impaired, accompanying with an increase of TEER and fluorescein sodium flux. MiR-18a was a direct target of RUNX1 and it could bind to the promoters of RUNX1 to inhibit the expression of Occuldin and ZO-1. Consistently, these phenomena could also be observed in the corresponding cell model. Conversely, miR-18a knockdown or RUNX1 overexpression just presented an improvement effect on ICH. CONCLUSIONS: MiR-18a plays a critical role during ICH because it targets to RUNX1 to inhibit the expression of tight junction proteins (Occludin and ZO-1) and then disrupt BBB permeability. MiR-18a might be a probable therapeutic target for ICH diseases.
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Barrera Hematoencefálica/metabolismo , Permeabilidad Capilar , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Hemorragias Intracraneales/metabolismo , MicroARNs/metabolismo , Ocludina/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Animales , Astrocitos/metabolismo , Astrocitos/patología , Barrera Hematoencefálica/patología , Células Cultivadas , Técnicas de Cocultivo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Modelos Animales de Enfermedad , Impedancia Eléctrica , Células Endoteliales/metabolismo , Células Endoteliales/patología , Hemorragias Intracraneales/genética , Hemorragias Intracraneales/patología , Masculino , MicroARNs/genética , Ocludina/genética , Ratas Sprague-Dawley , Transducción de Señal , Proteína de la Zonula Occludens-1/genéticaRESUMEN
A patient with thymoma associated immunodeficiency syndrome (Good's syndrome) and bronchiectasis was retrospectively analyzed. Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. It is important to bear in mind that Good's syndrome should be included in the differential diagnosis When patients repeatedly visited for bronchiectasis or infection, we should alert to their immune state and history of thymoma. Early screening of immunological status and aggressive correction of immune deficiency are beneficial to improving the prognosis to patients with Good's syndrome.
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Agammaglobulinemia , Bronquiectasia , Timoma , Neoplasias del Timo , Agammaglobulinemia/complicaciones , Bronquiectasia/complicaciones , Humanos , Estudios Retrospectivos , Timoma/complicaciones , Neoplasias del Timo/complicacionesRESUMEN
OBJECTIVE: The first-line treatment for epilepsy, a chronic neurological disorder characterized by spontaneous seizures, includes the application of anticonvulsant drug therapy. Only one-third of patients are incapable of complete controlling of their seizures after the administration of ≥2 pharmaceuticals. Here, we aimed to observe the ultrastructure changes and the expression of ZnT3 and GFAP in the hippocampus of drug-resistant epileptic rats. METHODS: A total of 50 healthy adult male SD rats were used to generate the model ofepilepsy by amygdala kindling. After the rats were successfully kindled, pharmacoresistant epileptic (PRE) rats were selected according to their response to phenobarbital and phenytoin. The ultrastructure as well as the expression of zinc transporter 3 (ZnT3, a member of a growing family of mammalian zinc transporters) and glial fibrillary acidic protein (GFAP) were compared among PRE, pharmacosensitive epileptic (PRE), and normal (NRC) rats. RESULTS: The PRE rats displayed severe synapses, neuronal degeneration, and necrosis. Moreover, the expression of ZnT3 and GFAP was significantly increased in both PRE and PSE rats; compared with NRC rats, the promotion of this expression was more pronounced in the PRE rats. CONCLUSIONS: Taken together, obvious synapses, neuronal degeneration, necrosis, mossy fiber sprouting, and astrogliosis were found in the drug-resistant epileptic rat model induced by amygdala kindling.
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Epilepsia , Preparaciones Farmacéuticas , Amígdala del Cerebelo , Animales , Epilepsia/inducido químicamente , Proteína Ácida Fibrilar de la Glía , Hipocampo , Humanos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To explore the changes and influencing factors about expressions of tumor-related gene mRNA in workers who smelt arsenic. METHODS: There were 37 workers who smelt arsenic, 43 workers who stopped exposure to arsenic for 85 days, and 51 individuals as control group which selected by random cluster sampling. Arsenic species( iAs, MMA, and DMA) in urine were determined by atomic absorption spectrophotometer with an As speciation pretreatment system. Real time PCR( RT-PCR)was performed to detect the expressions of 4 tumor-related gene mRNAs. RESULTS: The concentrations of iAs, MMA and DMA in urine of workers who smelt arsenic, stopped exposure to arsenic for 85 days, and control group were( 133. 97 ± 109. 53), ( 208. 93 ±171. 43) and( 820. 35 ± 487. 39) µg/( g·creatinine)( workers who smelt arsenic), ( 123. 31 ± 112. 72), ( 176. 21 ± 157. 19) and( 467. 73 ± 392. 17) µg/( g·creatinine)( workers who stopped exposure to arsenic), ( 1. 55 ±1. 49), ( 0. 10 ±0. 09) and( 10. 47 ±7. 85) µg/( g·creatinine)( control group). Compared to control group, the concentrations of 3 arsenic species were all higher in worker came from arsenic smelting. Compared to workers who were smelting arsenic, DMA are lower in workers who stopped exposure to arsenic for 85 days( P < 0. 05). The relative mRNA expressions of Lin28, Bax, Bcl-2 and Fas in 3 groups were( 8. 88 ± 2. 42), ( 6. 87 ± 1. 10), ( 7. 24 ± 2. 31) and( 8. 23 ±2. 90)( workers who smelt arsenic), ( 6. 21 ± 2. 94), ( 5. 81 ± 1. 72), ( 4. 50 ± 1. 59)and( 6. 89 ± 2. 35)( workers who stopped exposure to arsenic), ( 5. 60 ± 1. 43), ( 5. 56 ±0. 98), ( 4. 88 ± 1. 39) and( 6. 92 ± 1. 87)( control group). Compared to control group, relative mRNA expressions of Lin28, Bax, Bcl-2 and Fas were all higher in worker who were smelting arsenic( P < 0. 05). CONCLUSION: The expressions of tumor-related gene mRNAs are high in workers who smelt arsenic, and the methylation metabolism of arsenic play great role in the process of relative mRNAs expresses.
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Arsénico/toxicidad , Metilación/efectos de los fármacos , Neoplasias/inducido químicamente , Neoplasias/genética , Exposición Profesional/efectos adversos , ARN Mensajero/genética , Animales , Arsénico/orina , Arsenicales , Humanos , Espectrofotometría AtómicaRESUMEN
The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mammalian/mechanistic target of rapamycin complex 1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver. The Dermo1-Cre-driven Tsc2 conditional knockout mice had body growth retardation and died approximately 3 weeks after birth. Significant phenotypes were observed in the postnatal kidney and lung. Inactivation of Tsc2 in kidney mesenchyme caused polycystic lesions starting from the second week of age, with increased cell proliferation, tubular epithelial hyperplasia, and epithelial-mesenchymal transition. In contrast, Tsc2 deletion in lung mesenchyme led to decreased cell proliferation, reduced postnatal alveolarization, and decreased differentiation with reduced numbers of alveolar myofibroblast and type II alveolar epithelial cells. Two major findings thus result from this model: inactivation of Tsc2 in mesoderm-derived cells causes increased cell proliferation in the kidneys but reduced proliferation in the lungs, and inactivation of Tsc2 in mesoderm-derived cells causes epithelial-lined renal cysts. Therefore, Tsc2-mTOR signaling in mesenchyme is essential for the maintenance of renal structure and for lung alveolarization.
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Enfermedades Renales Poliquísticas/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Femenino , Humanos , Riñón/metabolismo , Riñón/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Mesodermo/patología , Ratones , Ratones Noqueados , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/patología , Serina-Treonina Quinasas TOR/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/genéticaRESUMEN
Deficiency in pulmonary surfactant results in neonatal respiratory distress, and the known genetic mutations in key components of surfactant only account for a small number of cases. Therefore, determining the regulatory mechanisms of surfactant production and secretion, particularly during the transition from prenatal to neonatal stages, is essential for better understanding of the pathogenesis of human neonatal respiratory distress. We have observed significant increase of bone morphogenetic protein (BMP) signaling in neonatal mouse lungs immediately after birth. Using genetically manipulated mice, we then studied the relationship between BMP signaling and surfactant production in neonates. Blockade of endogenous BMP signaling by deleting Bmpr1a (Alk3) or Smad1 in embryonic day 18.5 in perinatal lung epithelial cells resulted in severe neonatal respiratory distress and death, accompanied by atelectasis in histopathology and significant reductions of surfactant protein B and C, as well as Abca3, whereas prenatal lung development was not significantly affected. We then identified a new BMP-Smad1 downstream target, Nfatc3, which is known as an important transcription activator for surfactant proteins and Abca3. Furthermore, activation of BMP signaling in cultured lung epithelial cells was able to promote endogenous Nfatc3 expression and also stimulate the activity of an Nfatc3 promoter that contains a Smad1-binding site. Therefore, our study suggests that the BMP-Alk3-Smad1-Nfatc3 regulatory loop plays an important role in enhancing surfactant production in neonates, possibly helping neonatal respiratory adaptation from prenatal amniotic fluid environment to neonatal air breathing.
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Adaptación Fisiológica , Proteínas Morfogenéticas Óseas/fisiología , Pulmón/metabolismo , Surfactantes Pulmonares/metabolismo , Respiración , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Animales Recién Nacidos , Secuencia de Bases , Sitios de Unión , Expresión Génica , Pulmón/crecimiento & desarrollo , Ratones Endogámicos C57BL , Ratones Transgénicos , Regiones Promotoras Genéticas , Transducción de Señal , Proteína Smad1/metabolismo , Activación TranscripcionalRESUMEN
BACKGROUND: The effects of performing a minimally invasive procedure at different stages after intracerebral hemorrhage on perihematomal MMP-9 expression and blood-brain barrier (BBB) permeability were evaluated. METHODS: Sixty rabbits were randomly distributed into a model control group (MC group, 30 rabbits) or a minimally invasive group (MI group, 30 rabbits). A model of intracerebral hemorrhage was established in the MC and MI group. In the MI group, the intracerebral hematoma was evacuated by stereotactic minimally invasive procedures over 6 hours (6 rabbits), 12 hours (6 rabbits), 18 hours (6 rabbits) 24 hours or 48 hours (6 rabbits) following successful induction of intracerebral hemorrhage. The same procedure was performed in the MC group at the same time point but without evacuating the hematoma. All the animals were sacrificed within two weeks after the hematoma was surgically evacuated. A neurological deficit score was determined, and the perihematomal MMP-9 level and the BBB permeability were measured. RESULTS: The neurological deficit score, perihematomal MMP-9 level and BBB permeability of the MI group decreased significantly compared to the MC group. Performing the MI procedure 6-12 h after intracerebral hemorrhage showed the most favorable outcome. CONCLUSIONS: Regarding the pathophysiological changes surrounding the hematoma, the optimal time window of performing MI procedures for the intracerebral hematoma evacuation might be within 6-12 h after hemorrhage.
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Barrera Hematoencefálica/patología , Hemorragia Cerebral/cirugía , Metaloproteinasa 9 de la Matriz/metabolismo , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Neuroquirúrgicos/métodos , Animales , Agua Corporal , Hemorragia Cerebral/enzimología , Hemorragia Cerebral/patología , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Conejos , Técnicas Estereotáxicas , Terapia TrombolíticaRESUMEN
BACKGROUND: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA. OBJECTIVE: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE. METHODS: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, ß2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR. RESULTS: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, ß2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy. CONCLUSION: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Epilepsia Refractaria , Hipocampo , Ratas Sprague-Dawley , Receptores de GABA-A , Animales , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Epilepsia Refractaria/metabolismo , Ratas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Receptores de GABA-A/metabolismo , Receptores de GABA-A/biosíntesis , Pilocarpina/toxicidad , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Modelos Animales de Enfermedad , Fenobarbital/farmacologíaRESUMEN
Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24 h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.
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AIMS: Synaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure-induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis-inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF. METHODS: An intraperitoneal injection of lithium chloride-pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF. RESULTS: Parthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ-H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction. SIGNIFICANCE: SV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.
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Factor Inductor de la Apoptosis , Modelos Animales de Enfermedad , Epilepsia Refractaria , Glicoproteínas de Membrana , Proteínas del Tejido Nervioso , Ratas Sprague-Dawley , Animales , Ratas , Factor Inductor de la Apoptosis/metabolismo , Masculino , Proteínas del Tejido Nervioso/metabolismo , Epilepsia Refractaria/metabolismo , Epilepsia Refractaria/tratamiento farmacológico , Glicoproteínas de Membrana/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Anticonvulsivantes/farmacologíaRESUMEN
A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.
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Accumulating evidence suggests that patients with pulmonary lymphangioleiomyomatosis (PLAM) have a markedly higher prevalence of breast cancer (BC) than the general population. However, the underlying pathophysiological mechanisms remain unclear. Therefore, in this study, we employed a bioinformatics approach to understand the association between PLAM and estrogen receptor (ER)-positive BC. The PLAM (GSE12027) and ER-positive BC (GSE42568, GSE29044, and GSE29431) datasets were obtained from the Gene Expression Omnibus database, and GEO2R was used to identify common differentially expressed genes (DEGs) between them. Functional annotation was performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified and verified using western blotting and immunohistochemistry. We conducted an immune infiltration analysis; based on the results, selected 102 common DEGs for follow-up analysis. Functional analyses revealed that the DEGs were mostly enriched in cell proliferation, gene expression regulation, and tumor-related pathways. Four hub genes-ESR1, IL6, PLA2G4A, and CAV1-were further analyzed, and CAV1 was revealed to be associated with clinical outcomes and immune infiltration in ER-positive BC. This study proposes a common, possible pathogenesis of PLAM and ER-positive BC. These common pathways and pivotal genes may provide new directions for further mechanistic studies.
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Neoplasias de la Mama , Neoplasias de los Bronquios , Linfangioleiomiomatosis , Humanos , Femenino , Neoplasias de la Mama/patología , Perfilación de la Expresión Génica/métodos , Linfangioleiomiomatosis/genética , Mapas de Interacción de Proteínas/genética , Biología Computacional/métodos , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6-methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. However, the biomechanism of METTL14 in NSCLC is not very clear. METHODS: Here, immunohistochemical (IHC) assay was employed to detect METTL14 in NSCLC tissues. The biological functions of METTL14 were demonstrated using cell transfection, cell proliferation assay, cell clone formation assay, cell cycle analysis, cell death analysis, transwell and wound healing assays. Transcriptome and methylated RNA immunoprecipitation (MERIP)-sequencing were used to explore the pathways and potential mechanism of METTL14 in NSCLC. RNA sequencing, METTL14 rip-sequencing, and METTL14 merip-sequencing were conducted to identify the potential targets of METTL14. RESULTS: METTL14 was significantly correlated with clinical pathological parameters of differentiation and M stage. Additionally, METTL14 promotes cell proliferation, induces cell death, and enhances cell migration and invasion in vitro. Transcriptome and MeRIP-sequencing reveal oncogenic mechanism of METTL14. RIP-sequencing highlights CSF1R and AKR1C1 as targets of METTL14. After validation with TCGA dataset, colony stimulating factor 1 receptor (CSF1R) showed significant positive coefficient with METTL14, and was presumed to be one target of METTl14 in lung cancer and verified by the cellular experiments. CONCLUSION: In conclusion, our results revealed the clinical significance of m6A RNA modification atlas, the function, and molecular targets CSF1R of METTL14 in NSCLC cell lines. The RNA m6A methyltransferase METTL14 promotes the progression of NSCLC by targeted CSF1R.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , ARN , Proteínas Tirosina Quinasas Receptoras , ARN Mensajero , MetiltransferasasRESUMEN
BACKGROUND: PPARγ has been reported to participate in intracerebral hemorrhage (ICH) progression, and recruit RAD21 through binding DNA. Our study aimed to explore the roles of PPARγ/RAD21 in ICH and their related mechanisms. METHODS: ICH models in vitro and in vivo were established using thrombin and autologous blood injection, respectively. After that, rosiglitazone (RSG), GW9662, and RAD21 knockdown/overexpression plasmids were used to treat the ICH models. The cell apoptosis, the related inflammatory cytokines levels, and the neurological function of the rats were examined. Real-time quantitative PCR (RT-qPCR), western blot and immunofluorescence were employed to determine the expression of the M1/M2 polarization-related markers. Finally, the interaction of PPARγ and RAD21 in microglial cells was observed using double labeled immunofluorescence and co-immunoprecipitation. RESULTS: After thrombin induction, the cell apoptosis, and TNF-α, IL-1ß and IL-10 contents were all significantly increased (P < 0.05); whereas RSG and RAD21 overexpression evidently inhibited the apoptosis of thrombin-caused microglial cells, reduced TNF-α and IL-1ß contents, further increased IL-10 content (P < 0.05). The combination of RAD21 and PPARγ was enhanced by RSG and RAD21 overexpression. In vivo experiments showed that RSG and RAD21 overexpression decreased neurological deficit score, brain water content and hematoma volume. Additionally, RSG and RAD21 overexpression up-regulated the expression of PPARγ, RAD21, Arg1, KLF4, and TGF-ß, whereas down-regulated iNOS and CD32 expression. The actions of GW9662 and RAD21 knockdown were opposite to those of RSG and RAD21 overexpression. CONCLUSION: PPARγ/RAD21 may alleviate ICH progression through promoting M2-type polarization of microglial cells and inhibiting inflammatory response.
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Lesiones Encefálicas , Neoplasias Encefálicas , Ratas , Animales , PPAR gamma/metabolismo , Interleucina-10/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Microglía/metabolismo , Trombina/metabolismo , Trombina/farmacología , Rosiglitazona/uso terapéutico , Rosiglitazona/farmacología , Hemorragia Cerebral/metabolismo , Lesiones Encefálicas/metabolismo , Neoplasias Encefálicas/metabolismoRESUMEN
Objective: The prognostic role of perineural invasion (PNI) in resected non-small cell lung cancer (NSCLC) remains unclear. A meta-analysis was performed to compare the overall survival (OS) of patients with resected NSCLC with and without PNI. Methods: The PubMed, EMBASE, and Web of Science databases were systematically searched to identify relevant studies investigating the effect of PNI on OS in patients with resected NSCLC. Pooled hazard ratio (HR) and 95% confidence intervals (CI) were estimated using a random-effects model. Separate meta-analyses using adjusted or unadjusted HR for OS were performed using Stata/SE 12.0. Results: Eleven studies comprising 2,279 patients were included. In total, PNI was identified in 9% (median, 4%-31%) of patients with resected NSCLC. The unadjusted pooled effect of the PNI was significantly associated with worse OS (HR, 2; 95% CI, 1.65-2.43). Adjusting for potential confounders yielded a similar result, with OS being significantly worse (HR, 2.13; 95% CI, 1.8-2.51) for patients exhibiting PNI. Conclusion: This meta-analysis indicates that the PNI is a strong prognostic factor for unfavorable outcomes in patients with resected NSCLC. Further large-scale prospective lung cancer trials are required to validate these results.
RESUMEN
We explored the association between the serum level of cystatin C (CysC) at admission and short-term functional outcome in patients with hypertensive intracerebral hemorrhage (HICH) without chronic kidney disease (CKD). A total of 555 patients with HICH were consecutively recruited after admission and were followed-up for 3 months after admission. The primary outcome was poor functional outcome (modified Rankin Scale [mRS] score ≥ 3). The median serum CysC level in our cohort was 1.03 mg/L (interquartile range, .89-1.20). Patients were categorized into four groups according to the serum CysC quartiles. Multivariate logistic regression analysis revealed a negative association between serum CysC and poor functional outcome at 3-month follow-up (quartile [Q]1 vs. Q4: adjusted odds ratio [OR] = .260, 95% confidence interval [CI] = .098, .691, p < .001). The negative association between serum CysC and poor functional outcome at 3 months was more pronounced in subgroups with smaller hematoma volume (≤ 30 mL), and absence of secondary intraventricular hemorrhage (IVH). Addition of serum CysC to a model containing conventional risk factors improved the model performance with net reclassification index (NRI) of .426% (p < .001) and integrated discrimination improvement (IDI) of .043% (p < .001) for poor functional outcome. Serum CysC was found to be a negative predictor of poor short-term functional outcome in HICH patients independent of renal function.
Asunto(s)
Hipertensión , Hemorragia Intracraneal Hipertensiva , Humanos , Cistatina C , Tasa de Filtración Glomerular , Hipertensión/complicaciones , Hemorragia Cerebral/epidemiología , Riñón/fisiología , BiomarcadoresRESUMEN
The extraction of potassium from polyhalite ore (K2SO4·MgSO4·2CaSO4·2H2O) can help alleviate potassium resource shortages in China. In this study, the leaching behavior of potassium extracted from polyhalite ore in water was investigated using leaching experiments and kinetic analysis. The effects of various factors, such as liquid-to-solid ratio, leaching temperature, leaching time, and polyhalite ore particle size were comprehensively studied. It was found that high temperatures improved the reaction rate and efficiency at the beginning (1-15 min) but reduced the final leaching efficiency of potassium. And this phenomenon is discussed from the aspects of the dissolution-reprecipitation of potassium, newly formed solid products during the leaching process, and leaching thermodynamics. The leaching of potassium followed the Avrami model, with an apparent activation energy of 26.29 kJ/mol. Additionally, it was determined that the mixed controlled step (surface chemical reaction and diffusion) was the controlling step during potassium leaching. This study clarified the leaching mechanism of the polyhalite in water, and the causes of hindering the leaching of potassium were analyzed. The research results can provide theoretical reference and solutions for parameter design for the enhanced leaching process and selection of leaching agents in the future.