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Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.
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Nefropatías Diabéticas , Transición Epitelial-Mesenquimal , Proteínas de Homeodominio , Túbulos Renales , ARN Largo no Codificante , Transición Epitelial-Mesenquimal/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Humanos , Ratones , Túbulos Renales/metabolismo , Túbulos Renales/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Masculino , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glucosa/metabolismo , Glucosa/farmacología , Fibrosis , Ratones Endogámicos C57BL , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: Renal interstitial fibrosis (RIF) is one of the main features of diabetic nephropathy (DN), but the molecular mechanisms mediating RIF in DN has yet been fully understood. S100A8 and S100A9 are the proteins associated with immune and inflammation response. Here we reported the expression of S100A8 and S100A9 were significantly increased on tubular epithelial cells in diabetic kidneys through a proteomic analysis. METHODS: We detected the expression of S100A8/A9 in diabetic kidneys by using immunoblotting, real-time PCR and immunostaining. RNA silencing and overexpression were performed by using S100A8/A9 expression/knockdown lentivirus to investigate the connection between S100A8/A9 and epithelial to mesenchymal transition (EMT) process. We also identify the expression of TLR4/NFκB pathway-related molecules in the case mentioned above. Afterwards a CO-IP assay was used to verify that compound AB38b ameliorates the EMT by interfering S100A8/A9 expression. RESULTS: The expression of S100A8 and S100A9 were significantly increased on tubular epithelial cells in diabetic kidneys. S100A8/A9 knocking-down alleviate and over-expression promote the renal interstitial fibrosis of diabetic mice. Mechanically, high levels of S100A8/A9 expression in tubular epithelial cells during diabetic condition activated the TLR4/NF-κB signal pathway which promoted the EMT process and finally led to RIF progression. S100A8/A9 knockdown ameliorated RIF of diabetic mice. Further experiments revealed that compound AB38b inhibited the EMT progression of tubular epithelial cells induced by S100A8/A9 through interfering the expressions of S100A8/A9. CONCLUSIONS: Our study suggest that abnormal expression of S100A8/A9 in the disease condition promotes EMT process and RIF through TLR4/NF-κB signal pathway. Using small molecular inhibitor AB38b to inhibit the abnormal expressions of S100A8/A9 might be a novel therapeutic strategy in treating DN.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Ratones , Animales , Nefropatías Diabéticas/metabolismo , FN-kappa B/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Transición Epitelial-Mesenquimal , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Proteómica , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , FibrosisRESUMEN
This study uses an integrated model of resource conservation theory and social learning theory to explore the antecedents of hotel interns' perceptions of occupational stigma and to explore the mechanisms inherent to retention willingness. This study first manipulated relevant subjects' experimental materials through a contextual experiment and used a one-way ANOVA to test the effects of competence stereotypes and occupational stereotypes on hotel interns' stigma perceptions, respectively, and then used partial least squares structural equation modeling (PLS-SEM) as a statistical tool and the SmartPLS 3.0 program to validate the model of hotel interns' occupational stigma perceptions-intention. The effects of both competence stereotypes and occupational stereotypes on hotel interns' perceptions of occupational stigma were significant. The results of the partial least squares structural equation model showed that hotel interns' perceptions of occupational stigma significantly contributed to emotional exhaustion and that emotional exhaustion significantly influenced hotel interns' retention willingness, hotel interns' perceptions of occupational stigma had a significant effect on their retention willingness, while the role of emotional exhaustion as a mediating variable and occupational commitment as a moderator. The inner psychological and behavioral linkage mechanisms of hotel interns' occupational stigma perceptions and their retention willingness under COVID-19 were explored, and the resource dynamics operating mechanism and professional commitment were also confirmed.
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INTRODUCTION: This study proposed a model based on Izard's theory of differential emotions to examine the effects of heritage nostalgia on perceived authenticity towards tourist satisfaction and the moderation of self-congruity in Chinese niche tourism. METHODS: We examined descriptive statistics to obtain an overview of the sample by using computer program SPSS 22. Then, for evaluation, partial least squares structural equation modelling (PLS-SEM) was employed as the appropriate statistical tool, and the statistical approach was implemented using the Smart PLS 3.0 computer program. RESULTS: The results of partial least squares structural equation modelling showed that heritage nostalgia positively affects existential and object-based authenticity. Existential and object-based authenticity positively influences tourist satisfaction. Self-congruity positively moderates the relationship between existential or object-based authenticity and heritage nostalgia. CONCLUSION: The linkage mechanism of tourists' psychology and behavior in heritage tourism has been explored, the internal mechanisms such as heritage nostalgia, tourists' authenticity and tourists' satisfaction have been discovered, and the internal mechanism of tourists' consistency of psychology and behavior has also been explained.
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BACKGROUND: Circulating tumor cells (CTCs) hold huge potential for both clinical applications and basic research into the management of cancer, but the relationship between CTC count and cervical cancer prognosis remains unclear. Therefore, research on this topic is urgently required. OBJECTIVE: This study investigated whether CTCs were detectable in patients with cervical cancer and whether CTC count was an indicator of prognosis. METHODS: We enrolled 107 patients with pathologically confirmed cervical cancer. CTCs were detected after radiotherapy or concurrent cisplatin-containing chemotherapy in all patients. We evaluated all medical records and imaging data as well as follow-up information to calculate progression-free survival (PFS). PFS was defined as the time until first diagnosis of tumor progression or death. We also analyzed the relationship between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. RESULTS: CTCs were identified in 86 of 107 patients (80%), and the CTC count ranged from 0 to 27 cells in 3.2 mL blood. The median progression-free survival (PFS) was 43.1 months. Patients in which CTCs were detected had a significantly shorter PFS than CTC-negative patients (P = 0.018). Multivariate analysis indicated that CTC count was an independent negative prognostic factor for survival. However, no correlation was observed between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. CONCLUSION: CTC count is an independent negative prognostic factor for cervical cancer.
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Células Neoplásicas Circulantes/patología , Supervivencia sin Progresión , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Recuento de Células , Cisplatino/uso terapéutico , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Radioterapia/métodos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapiaRESUMEN
OBJECTIVE: To provide a more effective cryoprotective medium (CPM), effect of union of albumin and egg yolk on human sperm cryopreservation was studied. METHODS: Egg yolk-glycerol-sodium citrate was regarded as CPM of the control group and egg yolk-glycerol-sodium citrate with different concentrations of albumin (1, 2, 3, 4, 5 g/L) were regarded as CPMs of experiment groups. Before and after cryopreservation, sperm movement parameters were assessed by using computer-aided sperm analyzer (CASA) system, and then egg yolk-glycerol-sodium citrate group added 1 g/L albumin was selected, whose movement parameters were the best among the experimental groups, and egg yolk-glycerol-sodium citrateto group as the control to compare sperm survival rate, membrane integrity, function of mitochondrion and ultrastruction. RESULTS: Sperm in egg yolk-glycerol-sodium citrate added I g/L albumin showed significantly higher motility, viability than those in the control group and other experimental groups (P < 0.05). Sperm in egg yolk-glycerol-sodium citrate group added 1 g/L albumin had significantly higher survival rate, head unpigmenting rate than those in control group (P < 0.05). Sperm in egg yolk-glycerol-sodium citrate group added I g/L albumin manifested significantly higher succinate dehydrogenase (SDH) activity than that in control group (P < 0.05) and had better ultrastructure than that in control group. CONCLUSION: Union of two kinds of albumin and egg yolk has better effects on human sperm cryopreservation than those of solitary use of egg yolk. The action of albumin is related to its concentration, and albumin combining with egg yolk may have plus and complementary effects on human sperm cryopreservation.
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Albúminas , Yema de Huevo , Preservación de Semen/métodos , Adulto , Criopreservación , Humanos , MasculinoRESUMEN
AIM: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. METHODS: Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. RESULTS: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. CONCLUSION: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque.
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Erección Peniana/efectos de los fármacos , Piperazinas/farmacología , Vasodilatadores/farmacología , Animales , Electromiografía , Macaca mulatta , Masculino , Erección Peniana/fisiología , Pene/anatomía & histología , Pene/efectos de los fármacos , Purinas , Citrato de Sildenafil , SulfonasRESUMEN
OBJECTIVE: To obtain related pharmacodynamic data for the clinical experiment by observing the sexual activities of male rats after using sildenafil ciltrate through stomach irrigation. METHODS: Forty male Sprague-Dawley rats were distributed into 4 groups with different dosages (control with distilled water, low dosage: 0.08%, medium dosage: 0.24% and high dosage: 0.72%). After the male Sprague-Dawlay rats were mated with their female counterparts in pairs, the latent period of chasing, the frequencies of chasing in 60 minutes, the latent period of intercourse and the frequencies of intercourse in 60 minutes were recorded. RESULTS: Compared with the control, the frequencies of chasing were significantly increased and the latent periods of chasing were significantly shortened in both high dosage and medium dosage groups after using sildenafil (P < 0.01); The frequencies of intercourse in 60 minutes were significantly increased and the latent periods of intercourse were significantly shortened in all the groups after the use of sildenafil. CONCLUSIONS: The sexual activities of male rats treated with sildenafil were significantly activated.
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Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Conducta Sexual Animal/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Masculino , Purinas , Ratas , Ratas Sprague-Dawley , Citrato de Sildenafil , SulfonasRESUMEN
BACKGROUND: To relieve the side effects induced by the complete obstruction of the vas deferens, we created a filtering-type intra-vas device (IVD) which is made of materials composed of nano-SiO(2)-copper complex cross-linking polymer composites. STUDY DESIGN: Eight male beagle dogs were grouped into nonimplanted control group and IVD-implanted group. We tested the efficacy of the sperm filtering effect of the new IVD material for 12 months and examined the influence of the IVD materials on the cells of the vas deferens, epididymis and testis. RESULTS: The densities of sperm were reduced significantly after the IVD was implanted; no motile sperm were found after the third month. No obvious morphological changes were found in the cells of the vas deferens, epididymis and testis in the IVD-implanted group. CONCLUSIONS: The filtering-type nano-SiO(2)-copper complex/polymer composite IVD is able to filter the sperm of the male dogs, and the IVD material did not cause obvious damage to the cells of the male reproductive organs after 1 year of implantation.