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1.
Cell Prolif ; : e13702, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956970

RESUMEN

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

2.
Biochim Biophys Acta Mol Basis Dis ; 1869(7): 166761, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37247698

RESUMEN

Endometriosis is an estrogen-dependent, progesterone-resistant gynecological disease with an unknown pathogenesis. Compared to women without endometriosis, women with endometriosis have a remarkably high heme level in the peritoneal fluid. To further investigate the pathomechanisms of heme in endometriosis, we aimed to identify the dysregulated expression of heme-trafficking proteins, such as PGRMC1/2 that are also receptors that mediate the non-genomic responses to progesterone, and heme-degrading enzymes between ectopic endometrial stromal cells and their normal counterparts. We found that heme could regulate progesterone receptor-related gene expression. Functional human endometrial stromal cell experiments showed that heme promotes cell proliferation and migration in a heme oxygenase-1-independent manner; moreover, blocking oxidative phosphorylation/ATP generation could abolish these effects of heme in vitro, whereas intraperitoneal hemopexin administration could alleviate heme-triggered ectopic lesions in vivo. Therefore, heme likely mediates the induction of progesterone resistance and simultaneously induces endometriosis via the mitochondrial oxidative phosphorylation pathway.


Asunto(s)
Endometriosis , Enfermedades Uterinas , Femenino , Humanos , Progesterona/farmacología , Progesterona/metabolismo , Endometriosis/genética , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Endometrio/patología , Estrógenos/metabolismo , Proteínas de la Membrana/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
3.
BMC Infect Dis ; 22(1): 947, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36526990

RESUMEN

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiología , Tiempo de Internación , China/epidemiología , Factores de Riesgo , Estudios Retrospectivos
4.
Cell Mol Life Sci ; 79(3): 173, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35244789

RESUMEN

During embryo implantation, apoptosis is inevitable. These apoptotic cells (ACs) are removed by efferocytosis, in which macrophages are filled with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the relationship between efferocytosis-related metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here, we report positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum levels of IL-33 and sST2, along with IL-33 and ST2, efferocytosis and metabolism of dMΦs, from patients with normal pregnancies and unexplained recurrent pregnancy loss (RPL). We revealed disruption of the IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from patients with RPL. The dMΦs that engulfed many apoptotic cells secreted more sST2 and less TGF-ß, which polarized dMΦs toward the M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis-related metabolism of RPL dMΦs toward oxidative phosphorylation and exacerbated the disruption of the IL-33/ST2 signaling pathway. Metabolic disorders also lead to dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and secondary necrosis. We also screened the efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback axis of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation with mouse IL-33 reduced the embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for homeostasis of the microenvironment at the maternal-fetal interface.


Asunto(s)
Apoptosis , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Aborto Espontáneo/inmunología , Aborto Espontáneo/patología , Animales , Decidua/citología , Femenino , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33/sangre , Interleucina-33/deficiencia , Interleucina-33/genética , Macrófagos/citología , Macrófagos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Oligomicinas/farmacología , Fosforilación Oxidativa , Embarazo , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Tirosina Quinasa del Receptor Axl
5.
Genes (Basel) ; 12(2)2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33499090

RESUMEN

It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.


Asunto(s)
Aborto Habitual/genética , Variaciones en el Número de Copia de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Aborto Habitual/metabolismo , Adulto , Alelos , Biomarcadores , Aberraciones Cromosómicas , Biología Computacional/métodos , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Embarazo , Estudios Retrospectivos , Transducción de Señal , Adulto Joven
6.
Int J Biol Sci ; 17(1): 339-352, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390854

RESUMEN

Background: Cervical cancer is a common malignant disease in female patients accompanied by activation of autophagy in tumor cells. However, the exact regulatory factors of autophagy and its effects on the immune response remain unknown. Methods: The induction of autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine and epacadostat was detected by western blot analysis and by an autophagy detection kit. Following co-culture with pre-treated HeLa and SiHa cells, U937 cells were analyzed by flow cytometry to detect CD80, CD86, CD163 and CD206 expression and the induction of phagocytosis. Results: IFN-γ caused a significant increase in the autophagy levels of HeLa and SiHa cells by promoting indoleamine-2,3-dioxygenase-1 (IDO1) expression. The induction of phagocytosis in HeLa and SiHa cells and the expression levels of CD80 and CD86 in U937 cells were increased significantly following treatment with recombinant human IFN-γ. This effect was associated with the induction of tumor cell autophagy. IFN-γ treatment and IDO1 overexpression promoted tryptophan depletion and kynurenine accumulation in cervical cancer cells. The latter was more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophages. In vivo, IDO1 overexpression restricted tumor growth in C57 mice and enhanced the induction of phagocytosis in macrophages. Conclusions: IFN-γ promoted induction of autophagy and macrophage phagocytosis in cervical cancer cells possibly via IDO1 expression and kynurenine metabolism.


Asunto(s)
Autofagia , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interferón gamma/metabolismo , Quinurenina/metabolismo , Activación de Macrófagos , Neoplasias del Cuello Uterino/metabolismo , Femenino , Células HeLa , Humanos , Fagocitosis , Células U937 , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/mortalidad
7.
Neurol Sci ; 42(6): 2397-2409, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33057978

RESUMEN

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
8.
Acta Pharmacol Sin ; 41(11): 1457-1464, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32424239

RESUMEN

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.


Asunto(s)
Lesión Renal Aguda/prevención & control , Apoptosis/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Proteínas de Motivos Tripartitos/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Membrana Celular/metabolismo , Células Epiteliales , Femenino , Humanos , Yohexol/análogos & derivados , Riñón/patología , Túbulos Renales Proximales/citología , Masculino , Fosfatidilserinas/metabolismo , Sustancias Protectoras/metabolismo , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapéutico , Proteínas de Motivos Tripartitos/metabolismo
9.
Reproduction ; 158(3): 257-266, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31299634

RESUMEN

Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22 µmol/L, 95% confidence interval (CI): 12.54-16.71), compared with the EMS-free group (9.517 µmol/L, 95% CI: 8.891-10.1053). This abnormal accumulation was not associated with the color of PF, phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophages (pMφs) was observed in the EMS group. Consistently, a high-concentration (30 µmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low-concentration (10 µmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) and the CD14+ peripheral monocytes (CD14+ Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pMφs in EMS.


Asunto(s)
Líquido Ascítico/química , Endometriosis/metabolismo , Hemo/análisis , Macrófagos/metabolismo , Enfermedades Peritoneales/metabolismo , Fagocitosis/fisiología , Adulto , Endometriosis/patología , Femenino , Humanos , Macrófagos/patología , Persona de Mediana Edad , Adulto Joven
10.
Aging (Albany NY) ; 11(5): 1589-1601, 2019 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-30853665

RESUMEN

The ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) is an objective approach to predicting poor outcomes in acute ischemic stroke (AIS). The impact of TG/HDL-C on hemorrhagic transformation (HT) after AIS remains unknown. The aim of this study was to explore the accurate effect of TG/HDL-C on HT after AIS. We enrolled a total of 1423 patients with AIS in the training cohort from a prospective, consecutive hospital-based stroke registry. Of the 1423 patients, HT occurred in 155 (10.89%) patients. The incidence of HT after AIS was significantly increased when there were low levels of TG (P=0.016) and TG/HDL-C (P=0.006) in patients with AIS attributable to large artery atherosclerosis (LAA), but not in those who suffered from cardioembolic stroke. After adjustment for covariates, a lower TG/HDL-C (OR=0.53, 95%CI=0.20-0.93) that was more than TG alone (OR=0.61, 95%CI=0.27-0.98) independently increased the risk of HT in LAA. Furthermore, our established nomogram indicated that lower TG/HDL-C was an indicator of HT. These findings were further validated in the test cohort of 558 patients with AIS attributable to LAA. In summary, a low level of TG/HDL-C is correlated with greater risk of HT after AIS attributable to LAA.


Asunto(s)
Aterosclerosis/patología , Isquemia Encefálica/patología , HDL-Colesterol/sangre , Lipasa/sangre , Accidente Cerebrovascular/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
Am J Reprod Immunol ; 82(2): e13088, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30614132

RESUMEN

Efferocytosis, which is known as the phagocytic clearance of dying cells by professional as well as non-professional phagocytes, including a great number of intracellular/extracellular factors and signals, is interrelated with the immune system, contributing to local and systemic homeostasis, especially in tissues with high constitutive rates of apoptosis. Accumulating studies have indicated that immune dysregulation is associated with the pathogenesis of the female reproductive system, which causes preeclampsia (PE), recurrent spontaneous abortion (RSA), ruptured ectopic pregnancy, and so on. And some studies have revealed the pleiotropic and essential role of efferocytosis in these obstetrical disorders. More specifically, the occurrence and development of these diseases were in connection with some efferocytosis-related factors and signals, such as C1q, MBL, and IL-33/ST2. In this review, we systematically review the diverse impacts of efferocytosis in immune system and discuss its relevance to normal and pathological pregnancy. These findings may instruct future basic researches as well as clinical applications of efferocytosis-related factors and signals as latent predictors or therapeutic targets on the obstetrical disorders.


Asunto(s)
Apoptosis/inmunología , Fagocitos/inmunología , Fagocitosis/inmunología , Complicaciones del Embarazo/inmunología , Embarazo/inmunología , Aborto Habitual/inmunología , Animales , Femenino , Humanos , Interleucina-33/inmunología , Interleucina-33/metabolismo , Macrófagos/inmunología , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/inmunología , Glicoproteínas de Membrana/inmunología , Fagocitos/citología , Fagocitosis/fisiología , Preeclampsia/inmunología , Complicaciones del Embarazo/patología , Embarazo Ectópico/inmunología , Receptores de Complemento/inmunología
12.
Int J Mol Med ; 43(2): 945-955, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30569127

RESUMEN

Angiogenesis is an essential process involved in various physiological, including placentation, and pathological, including cancer and endometriosis, processes. Melatonin (MLT), a well­known natural hormone secreted primarily in the pineal gland, is involved in regulating neoangiogenesis and inhibiting the development of a variety of cancer types, including lung and breast cancer. However, the specific mechanism of its anti­angiogenesis activity has not been systematically elucidated. In the present study, the effect of MLT on viability and angiogenesis of human umbilical vein endothelial cells (HUVECs), and the production of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS), under normoxia or hypoxia was analyzed using Cell Counting kit 8, tube formation, flow cytometry, ELISA and western blot assays. It was determined that the secretion of VEGF by HUVECs was significantly increased under hypoxia, while MLT selectively obstructed VEGF release as well as the production of ROS under hypoxia. Furthermore, MLT inhibited the viability of HUVECs in a dose­dependent manner and reversed the increase in cell viability and tube formation that was induced by hypoxia/VEGF/H2O2. Additionally, treatment with an inhibitor of hypoxia inducible factor (HIF)­1α (KC7F2) and MLT synergistically reduced the release of ROS and VEGF, and inhibited cell viability and tube formation of HUVECs. These observations demonstrate that MLT may serve dual roles in the inhibition of angiogenesis, as an antioxidant and a free radical scavenging agent. MLT suppresses the viability and angiogenesis of HUVECs through the downregulation of HIF­1α/ROS/VEGF. In summary, the present data indicate that MLT may be a potential anticancer agent in solid tumors with abundant blood vessels, particularly combined with KC7F2.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Melatonina/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Biomarcadores , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipoxia
13.
Sci Rep ; 8(1): 13074, 2018 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-30166568

RESUMEN

The aim of this study was to investigate the diagnostic value of the platelet count-to-spleen volume ratio (PSR) for diagnosing hepatic fibrosis in patients with hepatocellular carcinoma (HCC). In this interim analysis of an on-going prospective study, 117 patients with HCC and with or without cirrhosis or fibrosis in different stages were analyzed. Fibrosis staging negatively correlated with PSR and the liver volume-to-spleen volume ratio (LSR), while it positively correlated with aspartate aminotransferase-to-platelet ratio index (APRI), Frons' index, S-index and a fibrosis index based on four factors (FIB-4). The area under the receiver operating characteristic curve (AUROC) was significantly larger for PSR (0.777) than LSR (0.633, P = 0.002). Among patients with significant fibrosis, AUROC for PSR did not differ significantly from the AUROCs for APRI (0.789, P = 0.825), Frons' index (0.674, P = 0.102), FIB-4 (0.704, P = 0.251) or S-index (0.696, P = 0.204). Among patients with severe fibrosis, AUROC was significantly higher for PSR (0.808) than for LSR (0.685, P = 0.003), Frons' index (0.673, P = 0.014), FIB-4 (0.684, P = 0.029), or S-index (0.672, P = 0.016); in contrast, the AUROC for PSR was not significantly different from that for APRI (0.739, P = 0.215). Among patients with cirrhosis, AUROC was significantly higher for PSR (0.814) than for LSR (0.671, P = 0.001) or S-index (0.679, P = 0.022), while the AUROC for PSR did not differ significantly from those for APRI (0.711, P = 0.105), Frons' index (0.722, P = 0.061) or FIB-4 (0.708, P = 0.079). Our results suggest that PSR may be a useful non-invasive model for diagnosing liver fibrosis stage in patients with HCC in China.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/patología , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Estadificación de Neoplasias , Curva ROC , Bazo/diagnóstico por imagen , Bazo/patología
14.
Reproduction ; 156(5): 397-404, 2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30087159

RESUMEN

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO). Furthermore, IDO+NK cells possessed lower NKp46 and NKG2D but higher IL-10 than that of IDO-NK. Co-culture with endometrial stromal cells (nESCs) from healthy control or ectopic ESCs (eESCs) from women with EMS led to a significant increase in the IDO level in NK cells from peripheral blood, particularly eESCs, and an anti-TGF-ß neutralizing antibody suppressed these effects in vitro. NK cells co-cultured with ESC more preferentially inhibited the viability of nESCs than eESCs did, and pretreating with 1-methyl-tryptophan (1-MT), an IDO inhibitor, reversed the inhibitory effect of NK cells on eESC viability. These data suggest that ESCs induce IDO+NK cells differentiation partly by TGF-ß, and that IDO further restricts the cytotoxicity of NK cells in response to eESCs, which provides a potential therapeutic strategy for EMS patients, particularly those with a high number of impaired cytotoxic IDO+NK cells.


Asunto(s)
Endometriosis/inmunología , Endometrio/inmunología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Células Asesinas Naturales/enzimología , Adulto , Líquido Ascítico/inmunología , Estudios de Casos y Controles , Células Cultivadas , Endometrio/citología , Femenino , Humanos , Persona de Mediana Edad , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptor 1 Gatillante de la Citotoxidad Natural/metabolismo , Células del Estroma/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Adulto Joven
15.
Am J Reprod Immunol ; 79(6): e12836, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29500844

RESUMEN

PROBLEM: To explore whether IL-33/ST2 axis modulates the polarization and efferocytosis of decidual macrophages (dMφs). METHOD OF STUDY: The phenotype characteristics of dMφs from both normal pregnant women and recurrent spontaneous abortion (RSA) patients were determined by real-time polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Then, the efferocytosis and expression of IL-33 and its receptor (ST2) in dMφs were analyzed by FCM. Finally, the effects of sST2, a decoy receptor for IL-33 that inhibits the IL-33/ST2 signaling pathway, on the polarization and efferocytosis of dMφs and human macrophage cell line U937 were investigated. RESULTS: Compared with normal pregnancy, dMφs from RSA patients presented a M1 phenotype with high secretion of IL-33, whereas the expression of ST2 decreased. However, dMφs from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells (DSCs) compared with dMφs from normal pregnancy patients. Treatment with recombinant human sST2 led to the up-regulation of M1 bias and efferocytosis ability of both normal dMφs and U937. CONCLUSION: This study indicates that IL-33 secreted by dMφs promotes M2 bias at the feto-maternal interface, and as a result, RSA might attribute to the disturbance of IL-33/ST2 axis and the enhancement of efferocytosis of dMφs subsequently.


Asunto(s)
Aborto Habitual/metabolismo , Aborto Espontáneo/metabolismo , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Fagocitosis/fisiología , Aborto Habitual/patología , Aborto Espontáneo/patología , Adulto , Apoptosis/fisiología , Línea Celular Tumoral , Femenino , Humanos , Embarazo , Transducción de Señal/fisiología , Células del Estroma/metabolismo , Células del Estroma/patología , Células U937 , Regulación hacia Arriba/fisiología
16.
Curr Neurovasc Res ; 13(1): 45-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26666638

RESUMEN

In patients with severe carotid artery stenosis, the effects of carotid artery reopening, achieved either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), on cognitive functions remain elusive. Herein, we conducted a prospective study to determine whether and to what extent CEA and CAS affected cognitive performance. Patients admitted to the Department of Neurology or Vascular Surgery in Nanjing First Hospital from December 2012 to March 2015 with a diagnosis of severe carotid artery stenosis (>70%) were included in the study. Among them, 77 patients underwent CEA, 81 patients underwent CAS, and 77 patients who refused to receive aforementioned interventions were enrolled in control group. Of note, all patients in this study received basic pharmacological treatment according to the American Heart Association/American Stroke Association guidelines. Cognitive functions were evaluated by a broad spectrum of neuropsychological tests including the Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and event related potential P300 on the day prior to and at 3 months after indicated intervention. When compared with basic pharmacological treatment, both CEA and CAS significantly increased the scores of MMSE and MoCA at 3 months following procedures. Meanwhile, a significant reduction of P300 score was also observed in patients underwent CEA or CAS. In addition, the changes in MMSE, MoCA and P300 scores over time between CEA and CAS groups were not statistically significant. Taken together, our findings suggest an improvement of cognitive functions following carotid artery reopening. Meanwhile, the beneficial effects of CEA and CAS on cognitive performance seem to be equivalent.


Asunto(s)
Estenosis Carotídea , Trastornos del Conocimiento , Stents Liberadores de Fármacos , Endarterectomía Carotidea , Anciano , Estenosis Carotídea/complicaciones , Estenosis Carotídea/tratamiento farmacológico , Estenosis Carotídea/cirugía , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/cirugía , Electroencefalografía , Potenciales Relacionados con Evento P300/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Estadísticas no Paramétricas , Resultado del Tratamiento
17.
J Stroke Cerebrovasc Dis ; 25(1): 49-56, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26409718

RESUMEN

BACKGROUND: The profile and 1-year outcome after acute ischemic stroke (AIS) in Nanjing, China, is uncertain. This study aimed to investigate the profile and outcome after 1-year follow-up of AIS in East China. METHODS: In a prospective cohort study, 2168 patients with AIS were recruited consecutively. The primary outcome was death or dependency defined as a modified Rankin Scale score of 3-6 at 12 months. Plausible risk factors of death or dependency, such as demographics, risk factors of cardiovascular diseases, clinical features, laboratory results, and complications after a stroke, were selected from available variables to perform multivariable logistic regression analyses. RESULTS: Eight hundred thirty-seven (38.6%) patients died or suffered from dependency. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03-1.05), history of diabetes mellitus (OR, 1.50; 95% CI, 1.10-2.04), prior stroke (OR, 2.08; 95% CI, 1.51-2.87), National Institutes of Health Stroke Scale (NIHSS) score (OR, 23.06; 95% CI, 14.24-37.34), estimated glomerular filtration rate (OR, 1.65; 95% CI, 1.02-2.66), pulmonary infection (OR, 2.98; 95% CI, 2.17-4.09), and gastrointestinal bleeding (OR, 7.81; 95% CI, 2.76-22.09) were significantly and independently associated with higher rates of mortality or disability (all P values < .05). Male gender (P values < .001) was the only factor associated with lower mortality or disability. CONCLUSIONS: The main dominating predictors for death or dependency were older age, female gender, diabetes mellitus, prior stroke, NIHSS score, estimated glomerular filtration rate, pulmonary infection, and gastrointestinal bleeding.


Asunto(s)
Daño Encefálico Crónico/epidemiología , Isquemia Encefálica/epidemiología , Anciano , Daño Encefálico Crónico/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , China/epidemiología , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/epidemiología , Cardiopatías/epidemiología , Hospitales Públicos/estadística & datos numéricos , Humanos , Hiperlipidemias/epidemiología , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Recurrencia , Sistema de Registros , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Resultado del Tratamiento
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