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1.
Int J Mol Sci ; 25(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39062760

RESUMEN

A small molecule disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the CSSC dihedral angle of the disulfide unit caused by diverse substituents directly affects the effectiveness of this technology platform as well as its own chemical stability. The highly stable open-loop relaxed type disulfide unit plays a limited role in drug delivery due to its low dihedral angle. Here, we have built a novel disulfide unit starship based on the 3,4,5-trihydroxyphenyl skeleton through trigonometric bundling. The intracellular delivery results showed that the trigonometric bundling of the disulfide unit starship effectively promoted cellular uptake without any toxicity, which is far more than 100 times more active than that of equipment with a single disulfide unit in particular. Then, the significant reduction in cell uptake capacity (73-93%) using thiol erasers proves that the trigonometric bundling of the disulfide starship is an endocytosis-independent internalization mechanism via a dynamic covalent disulfide exchange mediated by thiols on the cell surface. Furthermore, analysis of the molecular dynamics simulations demonstrated that trigonometric bundling of the disulfide starship can significantly change the membrane curvature while pushing lipid molecules in multiple directions, resulting in a significant distortion in the membrane structure and excellent membrane permeation performance. In conclusion, the starship system we built fully compensates for the inefficiency deficiencies induced by poor dihedral angles.


Asunto(s)
Disulfuros , Disulfuros/química , Humanos , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo , Endocitosis , Membrana Celular/metabolismo , Simulación de Dinámica Molecular
2.
J Obstet Gynaecol ; 44(1): 2402265, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39268975

RESUMEN

BACKGROUND: Non-invasive risk stratification for patients with endometrial carcinoma (EC) is important for developing personalised treatment plans. Our study aimed to explore the ability of quantitative MRI parameters to predict the risk stratification of EC patients based on molecular classification. METHODS: Fifty-three patients with histologically proven EC who underwent pelvic MRI and surgical treatment at our hospital between January 2020 and August 2022 were assessed. The tumour volume (TV) and uterine volume (UV) were estimated with the ellipsoid formula and used to calculate the tumour volume ratio (TVR). The mean apparent diffusion coefficient (ADC) of the tumour was measured on a workstation. Quantitative MRI parameters were compared among different risk groups via unpaired Student's t-tests or Mann-Whitney's U-tests. RESULTS: The TV and TVR were significantly different between the low- and high-risk groups (p < 0.001), and cut-off values of 5342 mm3 and 0.055 allowed the differentiation of the high-risk group from the low-risk group, with 77% and 85% sensitivity and 78% and 78% specificity, respectively. There was a significant difference in the ADC between the two groups (p = 0.026), and a cut-off value of 0.65 × 10-3 mm2/s allowed differentiation of the risk groups, with 93% sensitivity and 39% specificity. CONCLUSIONS: Quantitative MRI parameters such as the TV, TVR and ADC may be helpful in preoperatively assessing the risk stratification of patients with EC based on molecular classification.


For patients with endometrial carcinoma (EC), it is important to assess the risk stratification based on molecular classification for developing treatment plans, but risk stratification is obtained most accurately from postoperative samples. We used non-invasive and easily accessible quantitative parameters of magnetic resonance imaging for preoperatively evaluating the risk stratification in these patients. We found that the quantitative parameters may be helpful in preoperatively assessing the risk stratification of patients with EC on the basis of molecular classification.


Asunto(s)
Neoplasias Endometriales , Imagen por Resonancia Magnética , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/clasificación , Neoplasias Endometriales/diagnóstico por imagen , Persona de Mediana Edad , Medición de Riesgo/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Pronóstico , Carga Tumoral , Adulto , Estudios Retrospectivos , Sensibilidad y Especificidad
3.
Int J Mol Sci ; 24(19)2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37834180

RESUMEN

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10-11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10-4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.


Asunto(s)
Atresia Biliar , Infecciones por Citomegalovirus , Antígenos HLA , Humanos , Lactante , Atresia Biliar/complicaciones , Atresia Biliar/genética , Atresia Biliar/patología , Proteínas de Unión a Calmodulina/metabolismo , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/inmunología , Pueblos del Este de Asia , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Inmunoglobulina M/metabolismo , Antígenos HLA/genética
4.
Gynecol Endocrinol ; 38(12): 1114-1120, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36447368

RESUMEN

Background: This study aimed to compare the differences between reproductive endocrinologists (Repro-Endo) and obstetricians-gynecologists (Ob-Gyn; non-reproductive medicine specialty) in diagnosing, evaluating, and treating PCOS women with insulin resistance (IR).Methods: Repro-Endo and Ob-Gyn in China participated in this survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis.Results: The study analyzed 2412 survey responses (92.3% OB-Gyn; 98.5% women). Physician's age, hospital grade, specialty, and the number of PCOS patients who visit the physicians, revealed that Repro-Endo participants were more likely to suggest an oral glucose tolerance test (OR, 1.727; 95% CI, 1.272-2.345) as their first choice than Ob-Gyn participants. The most common treatments for patients with PCOS were lifestyle modification (>95%) and metformin use (>80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (46.5% vs. 23.5%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (12.5% vs. 1.6%).Conclusion: This survey identified knowledge gaps in metabolic screening for patients with IR and PCOS. Similarly, it highlights the need to improve IR management education for physicians caring for PCOS women.


Asunto(s)
Resistencia a la Insulina , Metformina , Síndrome del Ovario Poliquístico , Humanos , Femenino , Masculino , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Endocrinólogos , Glucemia , Ginecólogos , Obstetras , Metformina/uso terapéutico
5.
Pediatr Res ; 89(3): 694-700, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32380506

RESUMEN

BACKGROUND: Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS. We aimed to investigate association of NSD1 common single nucleotide polymorphisms (SNPs) with HSCR susceptibility in Chinese Han population. METHOD: We genotyped 15 SNPs encompassing NSD1 gene region in 420 HSCR patients and 1665 controls on Fludigm EP1 platform. Association analysis was performed between cases and controls. RESULT: Rs244709 was the most associated SNP with HSCR susceptibility of the sample set (PAllelic = 9.69 × 10-5, OR = 1.37, 95% CI: 1.17-1.61). Gender stratification analysis revealed that NSD1 SNPs were associated with HSCR in males, but not in females. The nonsynonymous coding SNP rs28932178 in NSD1 exon 5 represented the most significant signal in males (PAllelic = 6.43 × 10-5, OR = 1.42, 95% CI: 1.20-1.69). The associated SNPs were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. NSD1 expression levels were higher in aganglionic colon tissues than ganglionic tissues (P = 3.00 × 10-6). CONCLUSION: NSD1 variation conferred risk to HSCR in males, indicating SoS and HSCR may share common genetic factors. IMPACT: This is the first study to reveal that NSD1 variation conferred risk to Hirschsprung's disease susceptibility in males of Chinese Han population, indicating Sotos syndrome and Hirschsprung's disease may share some common genetic background. This study indicates more attention should be paid to the symptom of constipation in patients with Sotos syndrome. Our results raise questions about the role of NSD1 in the development of enteric nervous system and the pathogenesis of Hirschsprung's disease.


Asunto(s)
Predisposición Genética a la Enfermedad , Variación Genética , Enfermedad de Hirschsprung/genética , N-Metiltransferasa de Histona-Lisina/genética , Mutación , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico , Biopsia , China/epidemiología , Exones , Femenino , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Sitios de Carácter Cuantitativo , Riesgo , Síndrome de Sotos/genética
6.
J Obstet Gynaecol Res ; 47(3): 1145-1152, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33462940

RESUMEN

AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of intervention, while only one of 10 fatty liver participants in control group disappeared. CONCLUSIONS: In addition to improving the menstrual cycle, KD had the additional benefits of reducing blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional pharmacological treatment in women with PCOS and liver dysfunction who were obese.


Asunto(s)
Dieta Cetogénica , Hepatopatías , Síndrome del Ovario Poliquístico , Dieta Reductora , Femenino , Humanos , Obesidad/complicaciones , Proyectos Piloto , Síndrome del Ovario Poliquístico/complicaciones , Estudios Prospectivos
7.
FASEB J ; 33(3): 3378-3391, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30514107

RESUMEN

Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN-induced villus atrophy is accompanied by elevated expression of CUGBP, Elav-like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT-116 cells as an IEC model in vitro, we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self-adaptive expression pattern in IECs in vitro. Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT-116, Caco-2, and IEC-6 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell-cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT-116 and IEC-6 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1/p53 axis, which may be a potential therapeutic target for the treatment of TPN-induced villus atrophy.-Yan, J.-K., Zhang, T., Dai, L.-N., Gu, B.-L., Zhu, J., Yan, W.-H., Cai, W., Wang, Y. CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition.


Asunto(s)
Atrofia/tratamiento farmacológico , Atrofia/genética , Proteínas CELF1/genética , Proliferación Celular/efectos de los fármacos , Preparaciones de Acción Retardada/farmacología , Proteína p53 Supresora de Tumor/genética , Animales , Células CACO-2 , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Células Epiteliales/efectos de los fármacos , Fase G1/efectos de los fármacos , Fase G1/genética , Fase G2/efectos de los fármacos , Fase G2/genética , Células HCT116 , Humanos , Mucosa Intestinal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Masculino , Nutrición Parenteral Total/métodos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
8.
BMC Psychiatry ; 18(1): 345, 2018 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-30342524

RESUMEN

BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.


Asunto(s)
Demencia/etiología , Pérdida de Diente/psicología , Adulto , Anciano , Demencia/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Oportunidad Relativa , Análisis de Regresión , Factores de Riesgo
9.
Fish Physiol Biochem ; 43(2): 631-640, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27889848

RESUMEN

The Paramisgurnus dabryanus was exposed to 30 mmol L-1 NH4Cl solution and air to assessing the change of body ammonia and urea contents and the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST). After 48 h of ammonia exposure, ammonia concentration in the plasma, brain, liver and muscle were 3.3-fold, 5.6-fold, 3.5-fold and 4.2-fold, respectively, those of the control values. Plasma, brain, liver and muscle ammonia concentrations increased to 2.2-fold, 3.3-fold, 2.5-fold and 2.9-fold, respectively, those of control values in response to 48 h of aerial exposure. Within the given treatment (ammonia or aerial exposure), there was no change in plasma, brain and liver urea concentrations between exposure durations. The plasma ALT activity was significantly affected by exposure time during aerial exposure, while the liver ALT activity was not affected by ammonia or aerial exposure. Exposure to NH4Cl or air had no effect on either plasma or liver AST activity. Our results suggested that P. dabryanus could accumulate quite high level of internal ammonia because of the high ammonia tolerance in its cells and tissues, and NH3 volatilization would be a possible ammonia detoxification strategy in P. dabryanus. Urea synthesis was not an effective mechanism to deal with environmental or internal ammonia problem. The significant increase of ALT activity in plasma during aerial exposure, indicating that alanine synthesis through certain amino acid catabolism may be subsistent in P. dabryanus.


Asunto(s)
Alanina Transaminasa/metabolismo , Amoníaco/farmacocinética , Aspartato Aminotransferasas/metabolismo , Cipriniformes/metabolismo , Urea/metabolismo , Aire , Alanina Transaminasa/sangre , Amoníaco/sangre , Animales , Aspartato Aminotransferasas/sangre , Encéfalo/metabolismo , Cipriniformes/sangre , Proteínas de Peces/sangre , Proteínas de Peces/metabolismo , Hígado/metabolismo , Músculos/metabolismo , Urea/sangre
10.
Am J Physiol Cell Physiol ; 310(1): C54-65, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26491048

RESUMEN

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3'-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.


Asunto(s)
Proteínas CELF1/metabolismo , Cadherinas/biosíntesis , Proteína 1 Similar a ELAV/metabolismo , Células Epiteliales/metabolismo , Mucosa Intestinal/metabolismo , ARN Mensajero/metabolismo , Regiones no Traducidas 3' , Antígenos CD , Sitios de Unión , Proteínas CELF1/genética , Células CACO-2 , Cadherinas/genética , Proteína 1 Similar a ELAV/genética , Regulación de la Expresión Génica , Humanos , Permeabilidad , Biosíntesis de Proteínas , Interferencia de ARN , ARN Mensajero/genética , Factores de Tiempo , Transfección
11.
Cell Physiol Biochem ; 39(4): 1581-94, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27627102

RESUMEN

BACKGROUND AND AIMS: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. METHODS: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. RESULTS: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. CONCLUSIONS: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Proteína Forkhead Box O3/genética , Lipopolisacáridos/farmacología , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Aceite de Soja/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transporte Biológico , Células CACO-2 , Permeabilidad de la Membrana Celular/efectos de los fármacos , Emulsiones , Fluoresceína-5-Isotiocianato/química , Colorantes Fluorescentes/química , Proteína Forkhead Box O3/metabolismo , Regulación de la Expresión Génica , Humanos , Lipopolisacáridos/agonistas , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
12.
Cell Physiol Biochem ; 33(6): 1863-75, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24969755

RESUMEN

BACKGROUND/AIMS: The ubiquitin-specific peptidase USP22 mediates various cellular and organismal processes, such as cell growth, apoptosis, and tumor malignancy. However, the molecular mechanisms that regulate USP22 activity remain poorly understood. Here we identify STAT3 as a new USP22 interactor. METHODS: · We used western blotting and RT-PCR to measure key protein, acetylated STAT3, and mRNA levels in HEK293 and colorectal cancer cell lines transfected with expression plasmids or specific siRNAs. Co-immunoprecipitation was used to demonstrate protein-protein interaction and protein complex composition. RESULTS: USP22 overexpression down-regulated STAT3 acetylation by deubiquitinating SIRT1. The three proteins were found to be present in a single protein complex. SiRNA-mediated depletion of endogenous USP22 resulted in SIRT1 destabilization and elevated STAT3 acetylation. Consistent with this finding, USP22 also down-regulated the expression of two known STAT3 target genes, MMP9 and TWIST. CONCLUSION: We show that USP22 is a new regulator of the SIRT1-STAT3 signaling pathway and report a new mechanistic explanation for cross talk between USP22 and the SIRT1-STAT pathways.


Asunto(s)
Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Tioléster Hidrolasas/metabolismo , Acetilación , Western Blotting , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Microscopía Fluorescente , Unión Proteica , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Tioléster Hidrolasas/genética , Ubiquitina Tiolesterasa , Ubiquitinación
13.
Am J Pathol ; 182(2): 565-76, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23195431

RESUMEN

CD133 is widely expressed in colorectal cancer (CRC) tissues and cell lines. This protein has been used as a marker of CRC cancer stem cells, although the function and mechanism of CD133 in CRC invasion and metastasis remain unclear. In our study, we examined the role of CD133 in CRC invasion in vitro and investigated the mechanism involved in CD133-related invasion. CD133(high) and CD133(low) HCT116 cells were isolated, and the proliferation and invasive ability of these two subpopulations were tested. CD133(high) HCT116 cells exhibited greater proliferation and invasion compared with CD133(low) HCT116 cells. CD133 knockdown (using CD133 small-interfering [si]RNA) inhibited the invasive activity of CD133si-HCT116 cells. For the first time, we found that the expression of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) was down-regulated in CD133si-HCT116 cells. In addition, for the TIMP-2si-HCT116 cells (transfected with TIMP-2 siRNA), in vitro invasion was significantly decreased, whereas the expression of CD133 remained unchanged. Finally, the metalloproteinase 2 and MEK/ERK signaling pathways were examined, and no significant change was observed after the knockdown of CD133 or TIMP-2 in HCT116 cells. In conclusion, we demonstrated that CD133 plays an important role in HCT116 cell invasion, and for the first time, we found that CD133 knockdown significantly down-regulated TIMP-2 expression, which suggests that CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2.


Asunto(s)
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Péptidos/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Antígeno AC133 , Proliferación Celular , Separación Celular , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Técnicas de Silenciamiento del Gen , Células HCT116 , Humanos , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 2 de la Matriz/metabolismo , Invasividad Neoplásica , ARN Interferente Pequeño/metabolismo
14.
Int J Womens Health ; 16: 527-541, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38558831

RESUMEN

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.

15.
Zhonghua Zhong Liu Za Zhi ; 35(7): 486-90, 2013 Jul.
Artículo en Zh | MEDLINE | ID: mdl-24257297

RESUMEN

OBJECTIVE: Mouse tumors were subcutaneously transplanted into different mouse strains and their growth and metastatic properties were checked, to explore the possibility of establishing animal tumor models in different mouse strains other than their normal host strains. METHODS: Seven mouse tumor cell lines: H22, S180, U14, FC, Ca761, SMG-A and DCS were transplanted into C57BL/6J, ICR or KM mice, and their tumorigenicity, growth and metastasis were recorded and analyzed. RESULTS: The tumor formation rate of H22 cells in both the C57BL/6J and ICR mice was 100%, but the growth of H22 tumors was significantly faster in the C57BL/6J (2.8 ± 0.4)g than in the ICR mice (1.5 ± 0.5)g at the 17th day after transplantation (P<0.001). The S180 tumors grew stably in C57BL/6J mice and the tumor formation rate was 100%. The U14 inoculated into C57BL/6J and KM mice showed both lymphatic and lung metastasis and formed significantly larger tumors in KM mice [(12.6 ± 3.4)g] than that in the C57BL/6J mice [(10.2 ± 2.2)g] on the 32rd day after transplantation (P = 0.002). Transplantation of FC, Ca761, and SMG-A did not form tumors or the tumors were completely regressed later in C57BL/6J mice. DCS cells formed tumors in C57BL/6J mice, but some of the tumors regressed. The retained tumors were passaged in C57BL/6J mice, and the substrain DCS-C57 cells was established which showed stable growth and had a 100% tumor formation rate and 100% lung metastasis rate in C57BL/6J mice. CONCLUSIONS: Cross-strain transplanted tumors can be successfully established by inoculation of poorly differentiated and highly malignant tumor cells into different mouse strains. Some highly immunogenic tumor cells may form tumor, however, the tumors are regressed later, and can not establish cross-strain transplanted tumors in other mouse strains. Stable transplanted tumor models can be obtained from the partially regressed tumors after continuous passages in vivo.


Asunto(s)
Neoplasias Pulmonares/secundario , Regresión Neoplásica Espontánea/patología , Trasplante de Neoplasias , Neoplasias Experimentales/patología , Animales , Línea Celular Tumoral , Femenino , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Neoplasias Experimentales/clasificación , Trasplante Heterólogo , Carga Tumoral
16.
Zhongguo Gu Shang ; 36(12): 1153-8, 2023 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-38130224

RESUMEN

OBJECTIVE: To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT). METHODS: From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up. RESULTS: All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01). CONCLUSION: Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.


Asunto(s)
Lesiones del Manguito de los Rotadores , Articulación del Hombro , Músculos Superficiales de la Espalda , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Lesiones del Manguito de los Rotadores/cirugía , Manguito de los Rotadores , Resultado del Tratamiento , Articulación del Hombro/cirugía , Transferencia Tendinosa , Artroscopía , Rango del Movimiento Articular/fisiología
17.
Front Genet ; 14: 1186882, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37255715

RESUMEN

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 (JAG1) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population. Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1a and jag1b in biliary development were examined by morpholino knockdown in zebrafish. Results: Single nucleotide polymorphisms rs6077861 [P Allelic = 1.74 × 10-4, odds ratio = 1.78, 95% confidence interval: 1.31-2.40] and rs3748478 (P Allelic = 5.77 × 10-4, odds ratio = 1.39, 95% confidence interval: 1.15-1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model. Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA.

18.
Comput Math Methods Med ; 2022: 4010947, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35126622

RESUMEN

PURPOSE: To unravel mechanisms of miR-204-5p in breast cancer (BC) cells. METHODS: miR-204-5p expression level in BC cell lines was measured by qRT-PCR. Putative binding sites of miR-204-5p on the 3'-untranslated region of PRR11 were predicted by the bioinformatics method and verified by the dual-luciferase method. Protein and mRNA levels of PRR11 in BC were determined by western blot and qRT-PCR. The association between two genes was analyzed by correlation analysis. Cancer cell functions were evaluated through CCK8, flow cytometry, and Transwell approaches. RESULTS: Significant downregulation of miR-204-5p was observed in BC tissue and cells. Cell functional experiments showed the inhibition of miR-204-5p on cell behaviors and cell cycle. PRR11 was the downstream target of miR-204-5p. Inhibition of RPP11 could reverse the impacts of the miR-204-5p inhibitor on cell functions of BC. CONCLUSION: Our study revealed that the miR-204-5p/PRPP11 axis suppressed BC progression, which may provide a novel insight into the regulatory roles of miR-204-5p.


Asunto(s)
Neoplasias de la Mama/genética , Ciclo Celular/genética , MicroARNs/genética , Proteínas/antagonistas & inhibidores , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Biología Computacional , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
19.
Int J Womens Health ; 14: 1029-1036, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35959201

RESUMEN

Background: Primary dysmenorrhea (PD) is one of the most common complaints in women of childbearing age. Therefore, this trial aimed to assess the efficacy and safety of low-power visible-light-activated photodynamic therapy (PDT) in the treatment of primary dysmenorrhea (PD), and to further investigate their possible mechanisms of action. Methods: This study was conducted by using a multicenter, randomized, open, parallel control design. Qualified subjects are randomly assigned to two groups: Group A (low-power visible-light-activated PDT group), Group B (placebo group) and are treated with corresponding protocols for three consecutive menstrual cycles. Baseline data are collected during the trial period. Changes in the scores of VAS scales and the fluctuation of pain factors (PGE2, PGF2α) are recorded before and after the treatment for each group. A comparison of effectiveness in pain control and symptom control is made among the two groups. Results: After treatment, for the PDT group, the scores of VAS scales decline compared with the scores before treatment. The level of pain factors including PGE2 and PGF2α also drops significantly (P < 0.05). There are no serious adverse events during the study. Conclusion: Low-power visible-light-activated PDT is a new type of treatment for primary dysmenorrhea which is safe, effective and does not affect normal pregnancy preparation. It may exert its therapeutic effect by adjusting downward the level of PGE2, PGF2α in the body. These factors can be used not only to study the treatment mechanism for primary dysmenorrhea, but also to serve as quantitative indicators for objective assessment of whether dysmenorrhea is relieved.

20.
Front Immunol ; 13: 829760, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35350779

RESUMEN

Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.


Asunto(s)
COVID-19 , Líquido del Lavado Bronquioalveolar , Síndrome de Liberación de Citoquinas , Citocinas , Humanos , SARS-CoV-2
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