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The role of O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) in the pathogenesis of inflammatory bowel disease (IBD) has been increasingly highlighted in recent studies. It's been reported that signal transducer and activator of transcription 3 (STAT3) O-GlcNAcylation can affect the activity of the Janus kinase2 (JAK2)/STAT3 pathway.Our recent study showed that resveratrol repairsIBDin mice.On this basis,the present study aimed to explore whether the mechanism of IBD repair by resveratrol is associated with STAT3 O-GlcNAcylation. Pretreatment of colitis mice and intestinal epithelial cells with an O-GlcNAcylation promoter (Thiamet G, or Glucosamine) and an O-GlcNAcylation inhibitor (OSMI-1) showed that increased O-GlcNAcylation promoted colitis in mice.The pro-inflammatory cytokines interleukin (IL) -6, IL-1ß, and tumor necrosis factor-α (TNF-α) were increased, while the anti-inflammatory cytokine IL-10 was decreased. Moreover, the downstream target proteins of JAK2/STAT3, cyclooxygenase-2 and nitric oxide synthase 2 were up-regulated, Resveratrol treatment mitigated the inflammation by decreasing JAK2/STAT3 activity, as well as STAT3 O-GlcNAcylation. Finally, the correlation between STAT3 glycosylation and phosphorylation in intestinal epithelial cells under the effect of resveratrol was investigated by Immunofluorescence co-localization and immunoprecipitation.The results showed that resveratrol inhibited STAT3 O-GlcNAcylation, thereby inhibiting its phosphorylation, reducing JAK2/STAT3 pathway activity, and alleviating IBD.
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Colitis , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Factor de Transcripción STAT3/metabolismo , Resveratrol/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis/patología , Citocinas/metabolismo , Células Epiteliales/metabolismo , Janus Quinasa 2/metabolismoRESUMEN
Subarachnoid hemorrhage (SAH) is characterized by the extravasation of blood into the subarachnoid space, in which erythrocyte lysis is the primary contributor to cell death and brain injuries. New evidence has indicated that meningeal lymphatic vessels (mLVs) are essential in guiding fluid and macromolecular waste from cerebrospinal fluid (CSF) into deep cervical lymph nodes (dCLNs). However, the role of mLVs in clearing erythrocytes after SAH has not been completely elucidated. Hence, we conducted a cross-species study. Autologous blood was injected into the subarachnoid space of rabbits and rats to induce SAH. Erythrocytes in the CSF were measured with/without deep cervical lymph vessels (dCLVs) ligation. Additionally, prior to inducing SAH, we administered rats with vascular endothelial growth factor C (VEGF-C), which is essential for meningeal lymphangiogenesis and maintaining integrity and survival of lymphatic vessels. The results showed that the blood clearance rate was significantly lower after dCLVs ligation in both the rat and rabbit models. DCLVs ligation aggravated neuroinflammation, neuronal damage, brain edema, and behavioral impairment after SAH. Conversely, the treatment of VEGF-C enhanced meningeal lymphatic drainage of erythrocytes and improved outcomes in SAH. In summary, our research highlights the indispensable role of the meningeal lymphatic pathway in the clearance of blood and mediating consequences after SAH.
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Vasos Linfáticos , Ratas Sprague-Dawley , Hemorragia Subaracnoidea , Animales , Conejos , Hemorragia Subaracnoidea/metabolismo , Ratas , Masculino , Ligadura/métodos , Eritrocitos/metabolismo , Modelos Animales de Enfermedad , Factor C de Crecimiento Endotelial Vascular/metabolismo , Meninges , Edema Encefálico/metabolismoRESUMEN
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
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Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.
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Objective To establish and validate the nomogram prediction model of degenerative lumbar disc disease in young and middle-aged people.Methods From January 2020 to March 2022,232 young and middle-aged people who were examined with MRI of lumbar intervertebral disc and standard standing position lumbar anteroposterior and lateral X-ray films in Suzhou Ninth Hospital Affiliated to Soochow University were selected as the study subjects.Collecting the factors that may affect the occurrence of degenerative lumbar disc disease in young and middle-aged people,the people were divided into degenerative disease group(n=78)and non-degenerative disease group(n=154)according to the presence or absence of degenerative lumbar disc disease.Influencing factors were compared between the two groups,the independent influencing factors screened out by multifactor logistic regression,the nomograph model was constructed by R software,and the model verified.Results Among 232 young and middle-aged people included in this study,78(33.6%)had degenerative lumbar disc diseases.The results of multivariate logistic regression analysis showed that the increase of BMI,sedentariness,the increase of IL-1β level were the risk factors of degenerative lumbar disc disease in young and middle-aged people;the increase of pelvic incidence angle and the increase of miRNA-142-3p level were protective factors for degenerative lumbar disc disease in young and middle-aged people(P<0.05).The nomogram model was constructed according to the results of multifactor analysis.ROC results showed that AUC was 0.889(95%CI 0.844-0.933,P<0.05),the average absolute error of internal validation was 0.017,the prediction curve was basically fitted with the standard curve,and the H-L goodness of fit test showed that the model was consistent(P>0.05).The decision curve shows that the clinical benefit rate is the highest when the model prediction probability threshold is 0.16-0.80.Conclusions Degenerative lumbar disc disease in young and middle-aged people is affected by such factors as BMI,sedentariness,and incidence angle of pelvis,and the nomogram model established based on this has high differentiation and accuracy of prediction.
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Background: FOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM). Methods: Western blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene. Results: FOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased. Conclusion: FOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.
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The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.
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Humanos , Citocinas/genética , Enfermedades Inflamatorias del Intestino , FN-kappa B/metabolismo , Procesamiento Proteico-Postraduccional , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.
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Humanos , Enfermedad Crónica , Colitis Ulcerosa/terapia , Enfermedad de Crohn/epidemiología , Diarrea , Proteínas de Homeodominio , Enfermedades Inflamatorias del Intestino , Células Madre Mesenquimatosas/citología , MicroARNs , ARN Largo no Codificante , Recurrencia , Cordón Umbilical/citologíaRESUMEN
Objective To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. Methods Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. Results A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). Conclusions The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.
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Objective:To explore the characteristics of sleep disorders in patients with Parkinson's disease (PD) and its correlation with homocysteine.Methods:Totally 75 PD patients hospitalized in the department of neurology from January 2017 to June 2021 were selected and divided into sleep disorder group ( n=39) and non-sleep disorder group ( n=36)according to polysomnography, Parkinson's disease sleep scale(PDSS) and Epworth sleepiness scale(ESS). The basic clinical data, hematological examination results, scale evaluation data and polysomnography monitoring data of the above patients were collected during hospitalization to analyze the sleep characteristics of patients with Parkinson's disease and its correlation with homocysteine.SPSS 26.0 statistical analysis software was used for t test, Mann-Whitney U test, Pearson analysis, Spearman analysis and multivariate Logistic analysis. Results:The sleep efficiency (56.82±19.07)%, N2 phase ratio(48.67±17.70)%, N3 phase ratio(9.20%(19.00%)) and the leg movement micro-arousal index(0(1.20)) in the sleep disorder group were lower than those in the non-sleep disorder group (sleep efficiency (82.15±5.55)%, N2 phase ratio(57.02±2.80)%, N3 phase ratio(20.01%(3.93%)), the leg movement micro-arousal index(1.15(1.80)). The differences were statistically significant ( t/ Z=-6.087, -2.905, -3.773, -3.683, all P<0.05). The proportion of AHI (0.90(14.60)), N1 stage (19.50%(15.70%)), and periodic limb index (0(24.80)) in sleep disorder group were higher than those in non-sleep disorder group (AHI (0.60(0.30)), N1 stage (12.15%(3.15%)), and periodic limb index (0(0)). The difference was statistically significant ( Z=2.154, 5.250, 3.559, all P<0.05). The homocysteine (15.80(3.90) μmol/L), NMSS-insomnia correlation score (3.00(5.00)), MDS-UPDRS-Ⅰ(7.00 (10.00)), MDS-UPDRS-Ⅲ (23.00 (16.00)) in the sleep disorder group were higher than those in the non-sleep disorder group (homocysteine (14.10 (4.20)μmol/L), NMSS-insomnia correlation score (0(1.00)), MDS-UPDRS-Ⅰ(3.00 (2.00)), MDS-UPDRS-Ⅲ (17.00 (4.00)), and the differences were statistically significant( Z=2.557, 4.487, 2.952, 2.180, all P<0.05). The NMSS-olfactory correlation scores (2.00(4.00)) and PDSS (99.00 (40.00)) were lower than those in the non-sleep disorder group (NMSS-olfactory correlation scores (4.50 (7.00)) and PDSS (122.00 (28.00)), and the differences were statistically significant ( Z=2.450, 4.126, both P<0.05). Hcy was positively correlated with sleep disorder in PD patients ( r=0.297, P<0.05). Binariate logistic regression analysis showed that elevated homocysteine level might be a risk factor for sleep disorder in PD patients ( β=0.193, OR=1.213, 95% CI=1.029-1.430). Conclusion:Parkinson's disease patients with sleep disorder have the characteristics of sleep structure disorder, often accompanied by more serious motor disorders, and the olfactory function impairment is relatively mild. Elevated homocysteine levels may be a risk factor for sleep disorder in Parkinson's disease.
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Exosomas/metabolismo , Linfedema/terapia , Células Madre Mesenquimatosas/metabolismo , Animales , Exosomas/trasplante , Proteínas de Homeodominio/metabolismo , Humanos , Linfangiogénesis , Células Madre Mesenquimatosas/citología , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Cola (estructura animal)/patología , Trasplante Heterólogo , Proteínas Supresoras de Tumor/metabolismo , Proteínas de Transporte Vesicular/antagonistas & inhibidores , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Gelatina de Wharton/citologíaRESUMEN
By collecting and analyzing the explanation/conception, acupoint name, acupoint location, indications, acupuncture and moxibustion techniques and contraindications of
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Humanos , Acupuntura , Puntos de Acupuntura , Terapia por Acupuntura , Meridianos , MoxibustiónRESUMEN
A high performance liquid chromatography( HPLC) method was established for the fast,and precise determination of ten nucleosides in Fritillariae Cirrhosae Bulbus and its counterfeits. Then multivariate statistical analyses,such as clustering analysis,principal component analysis( PCA),and Fisher' s linear discriminant analysis( LDA),were conducted to establish a discriminant function model for an integrated analysis. The results indicated that data acquisition time of a single sample was shortened within 16 min by the HPLC method. In the range of 5-1 000 mg·kg~(-1),the mass concentrations of all nucleosides exhibited good linear relationships with the corresponding peak areas( R2> 0. 999). The spiked recoveries were in the range of 93. 83%-108. 9% with RSDs of0. 12%-1. 3%( n = 5). The limit of quantitation( LOQ) was 0. 98-4. 13 mg·kg~(-1). As revealed by the clustering analysis,Fritillariae Cirrhosae Bulbus and the counterfeits could be discriminated into two clusters based on the content of nucleosides. Fisher's LDA could achieve this discrimination,while PCA dimension reduction failed. The accuracy of the discriminant function model established on the screened characteristic indicators reached 97. 5%. The present study proposed a new identification method of Fritillariae Cirrhosae Bulbus with one-dimensional indicators,which is simple,accurate,and reliable. It can provide a scientific basis for further optimizing the identification techniques for Fritillariae Cirrhosae Bulbus and inspiration for quality control strategy development of Chinese medicinal materials.
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Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos , Fritillaria , Nucleósidos , Raíces de PlantasRESUMEN
Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.
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BACKGROUND AND AIM: Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS: FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS: The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/genética , Factores de Transcripción Forkhead/genética , Glioblastoma/genética , Glioblastoma/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Fenotipo , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective:To evaluate the effect of uncoupling protein 1 (UCP1) expression of perirenal fat on the prognosis of clear cell renal cell carcinoma (ccRCC) .Methods:From Feb. 2013 to Oct. 2013 and Mar. 2015 to Oct. 2015, 98 patients with ccRCC who underwent retroperitoneal laparoscopic radical nephrectomy were analyzed. UCP1 mRNA of perirenal fat around tumor was detected by RT-qPCR. Preoperative Computed tomography (CT) images were used to evaluate the thickness and adhesiveness of perirenal fat. According to the UCP1 mRNA value, the patients were divided into high UCP1 group (42 cases) and low UCP1 group (56 cases) . The general clinical data, perirenal fat thickness and adhesiveness were compared, and Kaplan Meier curve was used to evaluate the difference of progression free survival (PFS) between the two groups. Univariate and multivariate Cox analysis were used to determine the potential independent prognostic factors of PFS.Results:In the high UCP1 group, the renal fat thickness, the ratio of fat adhesion, the ratio of Ⅲ to Ⅳ in Fuhrman grade and the ratio of >T2 in T stage were higher than those in the low UCP1 group[ (13.84±2.41) vs (10.75±1.99) , 42.86% vs 16.07%, 28.57% vs 8.93%, 21.43% vs. 5.36%; P=0.000, P=0.003, P=0.011, P= 0.037]. During the follow-up period (median, 62.0 months) , 15 cases (12 cases of high UCP1 group, 3 case of low UCP1 group) developed tumor progression. Kaplan Meier curve showed that PFS of high UCP1 group was worse than that of low UCP1 group (71.43% vs 94.64%, P=0.001) . Cox regression analysis showed that high UCP1 expression and high T stage were significantly correlated with low PFS ( β=1.334, RR=3.796, 95% CI=1.009-14.280, P= 0.048; β=2.886, RR=17.930, 95% CI=5.538-58.047, P=0.000) . Conclusions:The increased UCP1 expression of perirenal fat may be an independent risk factor of tumor progression in ccRCC. Combined with the assessment of browning of perirenal adipose tissue may be helpful for risk stratification of ccRCC patients after surgery.
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Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.
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On the basis of the chromogenic reaction between Hg and CuI, a semi-quantitative solid sampling Hg analyzer comprising the catalytic furance, Hg testing tube, air pump and smart cellphone was developed. White carrier 101 was chosen as the adsorbent for CuI to react with Hg from the catalytic furnace. The established Hg analyzer can not only visually recognize the coloration when Hg exceeding the limit standard, but also semi-quantitatively detect the Hg content in cosmetics fast using a smart cellphone and RGB analysis software, after direct solid sampling introduction of cosmetics sample. The instrumental detection limit ( LOD) of mercury was 50 ng, the linearity ranged from 50 ng to 2500 ng, the linear regression coefficient ( R2) was higher than 0. 97, and the RSD of the corresponding RGB values was 6% ( n=11 ) . Nine real cosmetics samples were measured by the established method, whose relative differences of Hg contents with that by the standard method (Safety Technical Specification for Cosmetics, 2015 edition) were less than 10% . The whole analytical time can be controlled within 5 min. The established instrumental method is simple, fast, accurate and visual, and extremely suitable to fast and on-site monitoring of Hg in cosmetics samples.
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Chronic hyperglycemia is often accompanied by abnormal lipid metabolism, hypertension, low-grade systemic inflammation and oxidative stress.These factors increase the risk of cardiovascular disease(CVD)in type 2 diabetes mellitus(T2DM)patients.Comprehensive treatment of T2DM should emphasize the improvement of abnormal lipid metabolism, prevention of weight gain and reduction of the CVD risk in addition to proper glycemic control.Incretin, as a new hypoglycemic drug, has more advantages in improving glucose and lipid metabolism, finally to reduce cardiovascular risk.Through possible mechanisms including direct influence on liver lipid metabolism, change of fat mobilization and delay of gastric emptying, incretin shows positive influence on the lipid metabolic markers such as low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and total cholesterol, while it improves glucose control.Thus, incretin plays an important role in the comprehensive management of type 2 diabetes mellitus.
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<p><b>OBJECTIVE</b>To analyze the effect of globular adiponectin on angiogenesis of ovarian microvascular endothelial cells (OMECs).</p><p><b>METHODS</b>Mouse OMECs were isolated and purified by density gradient centrifugation with Percoll and identified by immunofluorescence analysis of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and endothelial cell marker von Willebrand factor (vWF). The capillary-like tube formation of OMECs was determined by vascular endothelial growth factor A (VEGFA) treatment in Matrigel matrix. OMECs treated with recombinant globular adiponectin protein were examined for cell proliferation with MTS assay and cell migration with scratch wound healing assay, and capillary-like tube formation was tested in Matrigel matrix. Western blotting was performed to detect the effect of globular adiponectin on AMPK phosphorylation.</p><p><b>RESULTS</b>The signals of LHR and vWF, but not that of FSHR, were detected in the isolated cells. VEGFA treatment of the cells induced capillary-like tube formation, indicating their properties of ovarian-specific endothelial cells. Treatment with 1 and 3 µg/mL of recombinant globular adiponectin significantly increased the number of OMECs by (158.72∓14.50) % and (186.50∓4.20)% (P<0.01) and resulted in scratch wound closure rates of (49.43∓3.43)% (P<0.05) and (69.67∓1.2) % (P<0.01) respectively. The cells treated with 3 µg/mL globular adiponectin formed a capillary-tube length 6.63∓0.66 folds greater than that formed by the control cells (P<0.01). Treatment of the cells with 3 µg/mL globular adiponectin for 15 and 30 min resulted in pAMPK/AMPK ratios of 0.86∓0.08 and 0.66∓0.13, respectively significantly higher than that in the control cells (0.13∓0.12, P<0.01). Compound C obviously suppressed the tube formation and AMPK phosphorylation induced by globular adiponectin.</p><p><b>CONCLUSION</b>Globular adiponectin promotes angiogenesis of OMECs through activation of the AMPK signal pathway.</p>