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1.
Nat Commun ; 15(1): 4237, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762492

RESUMEN

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/ß inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.


Asunto(s)
Antígeno B7-H1 , Proteínas del Choque Térmico HSC70 , Lisosomas , Proteínas del Choque Térmico HSC70/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Lisosomas/metabolismo , Animales , Ratones , Humanos , Femenino , Línea Celular Tumoral , Proteolisis , Endosomas/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Ratones Endogámicos C57BL , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno CTLA-4/metabolismo , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Membrana Celular/metabolismo , Proteínas de la Mielina , Proteínas con Dominio MARVEL
2.
J Transl Med ; 21(1): 894, 2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071307

RESUMEN

The immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects.


Asunto(s)
Linfocitos T CD8-positivos , Tumor Carcinoide , Humanos , Linfocitos T CD8-positivos/metabolismo , Antígeno B7-H1/metabolismo , Tumor Carcinoide/metabolismo , Microambiente Tumoral , Linfocitos Infiltrantes de Tumor/metabolismo , Pronóstico
3.
Signal Transduct Target Ther ; 8(1): 426, 2023 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-37925421

RESUMEN

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , ARN Circular , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Endoteliales/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/patología , Metástasis Linfática , Sumoilación/genética , Factores de Transcripción , ARN Circular/genética
4.
Cancer Med ; 12(13): 14025-14036, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37329224

RESUMEN

BACKGROUND: Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. METHODS: The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. RESULTS: The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). CONCLUSION: TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.


Asunto(s)
Carcinoma de Células Escamosas , Timoma , Neoplasias del Timo , Humanos , Pronóstico , Timoma/patología , Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias , Neoplasias del Timo/patología , Estudios Retrospectivos
5.
Org Biomol Chem ; 21(24): 4955-4961, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37272190

RESUMEN

Herein we described the catalytic epoxidation of α,ß-enone, with peroxide in situ generated, via a predominant single electron transfer and a minor energy transfer pathway. We use inexpensive natural vitamin B2 (riboflavin, RF) or its simple ester (riboflavin tetraacetate, RFT) as the photocatalysts, commonly used 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) as both the electron source and organic base, and ambient air as the terminal oxidant, under visible-light irradiation and room temperature.

6.
Thorac Cancer ; 14(15): 1339-1347, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37037477

RESUMEN

BACKGROUND: This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. METHODS: We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan-Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. RESULTS: With a median follow-up of 60 months (range: 1-128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty-three patients experienced recurrence or metastasis. The total 10-year progression-free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka-Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka-Koga stage in the type B2 subgroup. CONCLUSION: Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.


Asunto(s)
Timoma , Neoplasias del Timo , Humanos , Timoma/cirugía , Timoma/diagnóstico , Estudios Retrospectivos , Neoplasias del Timo/cirugía , Neoplasias del Timo/diagnóstico , Pronóstico , Supervivencia sin Progresión , Estadificación de Neoplasias , Resultado del Tratamiento
7.
J Agric Food Chem ; 71(1): 825-835, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36583663

RESUMEN

Per- and polyfluoroalkyl substances (PFASs) are a novel class of emerging persistent organic pollutants (POPs) owing to their environmental persistence and bioaccumulation. Red swamp crayfish is a major source of exposure to PFASs, while the dietary intake of PFASs from crayfish is still unclear. We investigated the concentrations of PFASs in 130 batches of crayfish and 100 environmental samples from Middle and Lower Reaches of the Yangtze River Delta. Seven Perfluoroalkyl carboxylic acids (PFCAs), 3 Perfluoroalkyl sulfonates (PFSAs), and 6:2 Cl-PFESA were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Meanwhile, PFASs exposure levels were examined concretely in four tissues of crayfish and different circulation links. The average daily intake (ADI) risk model was used to evaluate the human health risk of consuming crayfish and suggested that the risk of PFASs exposure is at a low level.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Animales , Humanos , Contaminantes Químicos del Agua/análisis , Astacoidea , Ríos , Cromatografía Liquida , Fluorocarburos/toxicidad , Fluorocarburos/análisis , Espectrometría de Masas en Tándem , Medición de Riesgo , Monitoreo del Ambiente/métodos , Ácidos Alcanesulfónicos/análisis
8.
Expert Rev Anticancer Ther ; 22(12): 1349-1355, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36373901

RESUMEN

OBJECTIVES: The present study explores an extremely rare disease, thymic mucosa-associated lymphoid tissue (MALT) lymphoma, for its characteristics and prognostic factors by analyzing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From 2000 to 2018, cases with a diagnosed thymic MALT lymphoma were extracted. Clinical characteristics, treatments, and survival patterns of these cases were analyzed. RESULTS: Thymic MALT lymphoma (n = 26) accounted for 0.09% of all MALT lymphomas. With a sex ratio of 0.53 (male/female), 68% white population was affected. Most cases were diagnosed with Ann Arbor stage I (50%), yet advanced-stage did not show worse prognosis (p = 0.236). Different treatment protocols did not influence the overall prognosis (p > 0.99). The 5- and 10- year overall survival rates were 83.1% and 78.2%, respectively. Older than 70 years may be an independent risk factor for overall survival (HR = 7.166 [95% CI 1.173-43.756], p = 0.033). CONCLUSION: Thymic MALT lymphoma is a highly rare disease with a favorable prognosis. Ann Arbor staging might not be appropriate to classify severity of this disease or its treatment. Older people may have worse survival. A standardized treatment mode needs to be established, and surgery could remain as the mainstay.


Asunto(s)
Linfoma de Células B de la Zona Marginal , Femenino , Humanos , Masculino , Anciano , Linfoma de Células B de la Zona Marginal/terapia , Enfermedades Raras
9.
J Thorac Dis ; 14(8): 2894-2907, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36071772

RESUMEN

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is a rare disease. The present meta-analysis aims at accumulating current evidence to explore the clinical characteristics, treatments, and prognoses of thymic MALT lymphoma. Methods: We searched seven databases for studies published between the start date of database establishment and September 15, 2021. We included studies of patients with histological diagnoses and excluded those without data specifically on thymic MALT lymphoma. The quality was analyzed using an assessment tool. All data were tabulated. Pooled proportion was obtained using random-effects model. Statistical analysis was performed on R statistic software. Results: Overall, 52 case reports and 13 case series were eligible. The quality of case reports was inferior to that of case series in terms of selection (P<0.001). Based on the analysis of patients in the case reports, age, gender, concurrent diseases, and tumor size did not differ between limited-stage and advanced-stage cases. Surgery is the mainstay to treat thymic MALT lymphoma. The surgical approach and extent did not influence the occurrence of events. Patients at Ann Arbor stage I were prone to not receiving postoperative therapy (P=0.011), though it may not reduce the occurrence of events (P=0.637). The five-year overall survival (OS) rate and five-year progression-free survival (PFS) rate were 97.2% and 88.4%, respectively. Patients with advanced-stage disease were more likely to suffer events (P=0.009). Conclusions: Thymic MALT lymphoma is an extremely rare disease with a favorable prognosis. Currently available evidence is insufficient to draw solid judgments about treatment and prognosis. However, patients may benefit if thymectomy is chosen as the primary treatment. In some patients, lymph node sampling or dissection should be considered. In addition, if the patient is at an advanced-stage, postoperative therapy should be considered.

10.
Foods ; 11(15)2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35954009

RESUMEN

Perchlorate is a well-known thyroid-disrupting chemical as well as an extremely stable inorganic pollutant widely distributed in the environment. Therefore, perchlorate posts potential risks to the environment as well as human health. Crayfish is a dominant aquatic food with increasing consumption levels in recent years. It is crucial to evaluate the accumulation of perchlorate with well-water-soluble properties in crayfish and to assess its health risks. In our present study, we obtained crayfish samples from cultivated ponds and markets based on the regions of the Middle and Lower Reaches of the Yangtze River. The perchlorate concentration was measured in all 206 samples using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Monte Carlo simulation was used to perform health risk assessments. The results indicated that perchlorate levels ranged from 7.74-43.71 µg/kg for cultivated crayfish and 4.90-16.73 µg/kg for crayfish sold in markets. The perchlorate accumulation mainly occurred in exoskeleton parts. All the HQ values were remarkable, at less than one-indicating that perchlorate exposure through the ingestion of crayfish does not pose an appreciable risk to human health.

11.
Front Nutr ; 9: 904557, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873419

RESUMEN

Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.

12.
Orphanet J Rare Dis ; 17(1): 215, 2022 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-35668481

RESUMEN

BACKGROUND: Thymic neuroendocrine tumors comprise a heterogeneous group of rare diseases. This study aimed to investigate the real-world clinicopathological features and treatment outcomes of thymic neuroendocrine tumors. RESULTS: A total of 104 patients diagnosed with thymic neuroendocrine tumors in a single institution from 1983 to 2021 were eligible. Fourteen (13.46%) and 28 (26.92%) patients diagnosed with thymic neuroendocrine tumors suffered from multiple endocrine neoplasia and ectopic adrenocorticotropic hormone syndrome, respectively. Ninety-seven (93.27%) patients underwent surgical resection, including 79 (81.44%) with radical resection. Except for 5 patients lost during follow-up, the 1-, 3- and 5-year overall survival rates were 91.8%, 70.2% and 54.6%, respectively. The median overall survival was 61.57 months. Multivariate analysis revealed that years at diagnosis (HR 0.559, 95% CI 0.364-0.857, p = 0.008), radical resection (HR 2.860, 95% CI 1.392-5.878, p = 0.004), pathological grade (HR 1.963, 95% CI 1.058-3.644, p = 0.033) and Masaoka-Koga stage (HR 2.250, 95% CI 1.548-3.272, p = 0.000) exerted significant differences in overall survival among 99 patients. In the surgery group, multivariate Cox regression analysis exhibited significant overall survival differences in years at diagnosis (HR 0.563, 95% CI 0.367-0.866, p = 0.009), neoadjuvant therapy (HR 0.248, 95% CI 0.071-0.872, p = 0.030), radical resection (HR 3.674, 95% CI 1.685-8.008, p = 0.001), pathological grade (HR 2.082, 95% CI 1.098-3.947, p = 0.025) and Masaoka-Koga stage (HR 2.445, 95% CI 1.607-3.719, p = 0.000). CONCLUSIONS: Radical resection and Masaoka-Koga stage were independent prognostic factors for the survival of patients with thymic neuroendocrine tumors. Systemic therapy and integrated management of patients with advanced-stage disease require high-level clinical evidence.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias del Timo , Humanos , Estadificación de Neoplasias , Tumores Neuroendocrinos/patología , Pronóstico , Estudios Retrospectivos , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Resultado del Tratamiento
14.
Expert Rev Anticancer Ther ; 22(2): 215-228, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34596477

RESUMEN

BACKGROUND: For early stage non-small cell lung cancer, whether limited resection can yield comparable outcomes to those of lobectomy hasn't been established. We compared Overall survival (OS) and lung cancer-specific survival (LCSS) after segmentectomy or lobectomy in stage IA1 (≤10 mm) lung adenocarcinoma (LUAD) patients. RESEARCH DESIGN AND METHODS: We retrospectively recruited patients who'd been diagnosed with lung cancer for the first time and treated with segmentectomy or lobectomy, with or without previous other malignancy. RESULTS: 1788 patients were included. After propensity score matching: 5-year OS were 85.6% for segmentectomy and 84.7% for lobectomy (p=0.951); 5-year LCSS were 93.5% for segmentectomy; and 93.0% for lobectomy (p=0.726). Cox regression analysis revealed segmentectomy was comparable to lobectomy in OS and LCSS. Having a second lung cancer later in life was associated with a worse LCSS for lobectomy (p<0.05) rather than segmentectomy. After patients were stratified according to malignancy history, subgroup analyses showed no significant prognosis differences between two surgeries. CONCLUSIONS: For stage IA1 LUAD patients who were diagnosed with lung cancer for the first time, with or without previous other malignancy, segmentectomy yields comparable outcomes to those of lobectomy. It may provide better outcomes for patients with multiple suspicious nodules.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Neumonectomía , Estudios Retrospectivos , Programa de VERF
15.
Cancer Manag Res ; 13: 8527-8534, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34803401

RESUMEN

BACKGROUND: Given the lack of evidence-supported guidance for therapeutic recommendations of primary mediastinal malignant germ cell tumors (PMMGCTs), our study aimed to investigate the clinicopathological features, treatment strategies, and prognostic factors of PMMGCTs. METHODS: We carried out a consecutive retrospective evaluation on a series of patients diagnosed with PMMGCTs in Peking Union Medical College Hospital from January 2000 to August 2020. RESULTS: A total of 58 patients were eligible, consisting of 51 males and seven females. There were 15 patients with seminomas, 39 with nonseminomatous germ cell tumors (NSGCTs), and four with mixed germ cell tumors (GCTs). The 5-year overall survival was 45%, with a median survival time of 32.37 months. Except for the lost follow-up of seven patients, a univariate analysis of overall survival on the remaining patients showed significant differences in pathological type (mixed GCTs were regarded as NSGCTs) (p=0.036), tumor size (>11cm) (p=0.006), and other sites metastases (OSM) (p=0.001), respectively. Multivariate Cox regression analysis revealed that OSM and surgical resection were independently associated with overall survival in all kinds of PMMGCTs. CONCLUSION: OSM was an independent risk factor for patients with PMMGCTs. Surgery was proved to contribute to long-term survival. More in-depth clinical evidence is urgently needed to guide the treatment of PMMGCTs.

16.
Cells ; 10(8)2021 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-34440645

RESUMEN

Mitochondria play an essential role in supplying energy for the health and survival of neurons. Mitophagy is a metabolic process that removes dysfunctional or redundant mitochondria. This process preserves mitochondrial health. However, defective mitophagy triggers the accumulation of damaged mitochondria, causing major neurodegenerative disorders. This review introduces molecular mechanisms and signaling pathways behind mitophagy regulation. Furthermore, we focus on the recent advances in understanding the potential role of mitophagy in the pathogenesis of major neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's, etc.) and aging. The findings will help identify the potential interventions of mitophagy regulation and treatment strategies of neurodegenerative diseases.


Asunto(s)
Mitocondrias/patología , Mitofagia , Degeneración Nerviosa , Enfermedades Neurodegenerativas/patología , Neuronas/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Humanos , Mitocondrias/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Transducción de Señal
17.
Virol Sin ; 36(6): 1421-1430, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34228261

RESUMEN

Coronaviruses (CoVs) are important human and animal pathogens that cause respiratory and gastrointestinal diseases. Porcine epidemic diarrhoea (PED), characterized by severe diarrhoea and vomiting in pigs, is a highly lethal disease caused by porcine epidemic diarrhoea virus (PEDV) and causes substantial losses in the swine industry worldwide. However, currently available commercial drugs have not shown great therapeutic effects. In this study, a fluorescence resonance energy transfer (FRET)-based assay was applied to screen a library containing 1,590 compounds and identified two compounds, 3-(aminocarbonyl)-1-phenylpyridinium and 2,3-dichloronaphthoquinone, that target the 3C-like protease (3CLpro) of PEDV. These compounds are of low molecular weight (MW) and greatly inhibited the activity of this enzyme (IC50 values were obtained in this study). Furthermore, these compounds exhibited antiviral capacity against another member of the CoV family, feline infectious peritonitis virus (FIPV). Here, the inhibitory effects of these compounds against CoVs on Vero cells and feline kidney cells were identified (with EC50 values) and cell viability assays were performed. The results of putative molecular docking models indicate that these compounds, labeled compound 1 and compound 2, contact the conserved active sites (Cys144, Glu165, Gln191) of 3CLpro via hydrogen bonds. These findings provide insight into the antiviral activities of compounds 1 and 2 that may facilitate future research on anti-CoV drugs.


Asunto(s)
Antivirales/farmacología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Infecciones por Coronavirus , Coronavirus Felino , Enfermedades de los Porcinos , Animales , Gatos , Chlorocebus aethiops , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/veterinaria , Coronavirus Felino/efectos de los fármacos , Simulación del Acoplamiento Molecular , Porcinos , Enfermedades de los Porcinos/virología , Células Vero
18.
J Int Med Res ; 48(2): 300060519868628, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31448662

RESUMEN

OBJECTIVE: Popliteal artery entrapment syndrome is a rare cause of popliteal artery aneurysms. We present a rare case of a false aneurysm associated with popliteal artery entrapment syndrome that was treated with endovascular repair that initially failed. CASE REPORT: A 60-year-old man with a false popliteal artery aneurysm and limb ischemia was treated with endovascular repair that initially failed. The popliteal artery was suspected to be compressed by an abnormal bundle of muscle according to the findings of a subsequent magnetic resonance imaging examination. The popliteal artery was entrapped by an abnormal slip of the medial gastrocnemius muscle head. Parts of the popliteus muscle were also involved in compression of the popliteal artery, which was not distinguished on preoperative magnetic resonance imaging. Thus, the patient was diagnosed with a mixed type of popliteal artery entrapment syndrome (types III and IV). Bypass with the small saphenous vein was then performed. The patient was finally discharged with satisfactory relief of his ischemic symptoms. CONCLUSION: Popliteal artery entrapment syndrome should be considered before treating popliteal artery aneurysms, especially atypical pseudoaneurysms without significant atherosclerosis. Definitive surgical management rather than endoluminal treatment is required unless combined with open decompressive surgery to correct the musculotendinous anatomy.


Asunto(s)
Aneurisma Falso , Aneurisma , Arteriopatías Oclusivas , Síndrome de Atrapamiento de la Arteria Poplítea , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/cirugía
19.
Ann Vasc Surg ; 66: 309-317, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31863951

RESUMEN

BACKGROUND: This study analyzes the demographics of patients affected by Takayasu arteritis (TA). The study further explores the correlation and other contributory factors to the regional differences between the ratios of females to males (sex ratio). METHODS: This was a retrospective study using 1,011 clinical cases diagnosed with TA (as per 1990 American College of Rheumatology criteria) between 1982 and 2015 collected from the Peking Union Medical College Hospital (PUMCH) database. Literature review of TA studies published from 1992 to 2016 via the PubMed search was also conducted with exclusion of the studies less than 50 cases. General characteristics, sex ratios and regional differences worldwide, sex ratio variation in different age group, relationship between sex ratio and gross domestic product (GDP) per capita, and main lesion involved in different sexual group were statistically analyzed. RESULTS: The average age of these 1,011 patients was 32.5 ± 15.1 years, with 763 women comprising 75.5% of the cohort, giving a female-to-male ratio (F:M ratio) of 3.1:1. The F:M ratio of TA patients at PUMCH was equal to that of a previous study from China, but significantly lower than that in Japan, Italy, Turkey, Mexico, Korea (all P < 0.05), but higher than that in India (P < 0.05), and Thailand (although not statistically significant at P = 0.08). The sex ratio of TA patients between PUMCH and Japanese databases significantly differed at all age groups (P < 0.05), with the exception of the youngest (≤9 years; P = 0.57) and oldest (≥70 years; P = 0.32) patients. A significant correlation between the TA F:M ratio and GDP per capita was observed, with a correlation coefficient of ρ = 0.730 (P = 0.04). A sex difference in lesion distribution was also observed: women had significantly more aortic arch involvement (P = 0.02), whereas lower limb artery involvement was more frequent in men (P < 0.001). CONCLUSIONS: The sex ratio of patients with TA in China significantly differed from that in many other countries. Genetics, dietary habits, and environmental conditions may affect the incidences of TA in female versus male patients. Aortic arch branch vessels are involved more frequently in women; renal artery and iliac artery involvements are more common in men.


Asunto(s)
Salud Global , Arteritis de Takayasu/epidemiología , Adolescente , Adulto , Anciano , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Arteritis de Takayasu/diagnóstico , Factores de Tiempo , Adulto Joven
20.
World J Clin Cases ; 7(13): 1671-1676, 2019 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-31367626

RESUMEN

BACKGROUND: Innominate artery aneurysms (IAAs) are relatively rare. Endovascular therapy has been an alternative to open surgery in some IAA cases, but open repair is still necessary in complicated cases. CASE SUMMARY: We report a 35-year-old female who suffered from Takayasu's arteritis. The patient did not get regular treatment, and IAA and right common carotid artery aneurysm developed, which complicated with occlusion of the left carotid artery, subclavian artery, and the initial part of the left vertebral artery. The patient also had moderate aortic valve insufficiency. With inflammation being controlled well, the patient received the surgery for arterial aneurysms of innominate and right common carotid arteries and aortic valve insufficiency. The shunts for cerebral blood supply were designed to protect the brain and the surgery was conducted successfully under extracorporeal circulation. CONCLUSION: The case illustrates that open surgery may be appropriate for some complicated IAAs, and brain protection is important.

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