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OBJECTIVE: To explore the mechanism by which soybean isoflavone (SI) reduces calcium overload induced by cerebral ischemia-reperfusion (I/R). METHODS: Forty-eight SD rats were randomized into 4 groups to receive sham operation, cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion (I/R model group), or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+ signaling pathway.Calcium levels and pathological changes in the ischemic penumbra (IP) were measured using calcium chromogenic assay and HE staining, respectively.Another 72 SD randomly allocated for sham operation, I/R modeling, or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter, and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining, and ROS level, Ca2+ level, cell apoptosis, and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry; the protein expressions of Wnt5a, Frizzled-2, and P-CaMK â ¡ in the IP were detected with Western blotting and immunohistochemistry. RESULTS: In rats with cerebral I/R, Frizzled-2 knockdown significantly lowered calcium concentration (P < 0.001) and the expression levels of Wnt5a, Frizzled-2, and P-CaMK â ¡ in the IP area.In soy isoflavones-pretreated rats, calcium concentration, ROS and MDA levels, cell apoptosis rate, cerebral infarct volume, and expression levels of Wnt/Ca2+ signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group. CONCLUSION: Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+ signaling pathway.
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Isquemia Encefálica , Calcio , Glycine max , Isoflavonas , Ratas Sprague-Dawley , Daño por Reperfusión , Vía de Señalización Wnt , Animales , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Ratas , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Vía de Señalización Wnt/efectos de los fármacos , Isquemia Encefálica/metabolismo , Calcio/metabolismo , Glycine max/química , Apoptosis/efectos de los fármacos , Masculino , Proteína Wnt-5a/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
INTRODUCTION: Surgical site infections (SSIs) are significant postoperative risks; antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class III wounds, as there is currently a lack of evidence in the existing literature. METHODS: A multi-centre randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China, including 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. RESULTS: A total of 440 participants (median (interquartile range, IQR) age, 63.0 (54.0, 70.0) years; 282 males (64.09%); 437 patients were of Han race (99.32%) and were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 (14.49%) vs 52 (23.01%); risk difference, 1.76%, 95% confidence interval (CI) 1.08-2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 (5.61%) vs 31 (13.37%); risk difference, 2.68%; 95% CI 1.34-5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). CONCLUSION: The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole to be a valuable prophylactic antibiotic. Our findings provide valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.
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PURPOSE: Obesity and a high body mass index (BMI) are considered as risk factors for abdominal wall hernia (AWH). However, anthropometric measures of body fat distribution (BFD) seem to be better indicators in the hernia field. This Mendelian randomization analysis aimed to generate more robust evidence for the impact of waist circumstance (WC), body, trunk, arm, and leg fat percentages (BFP, TFP, AFP, LFP) on AWH. METHODS: A univariable MR design was employed and the summary statistics allowing for assessment were obtained from the genome-wide association studies (GWASs). An inverse variance weighted (IVW) method was applied as the primary analysis, and the odds ratio value was used to evaluate the causal relationship between BFD and AWH. RESULTS: None of the MR-Egger regression intercepts deviated from null, indicating no evidence of horizontal pleiotropy (p > 0.05). The Cochran Q test showed heterogeneity between the genetic IVs for WC (p = 0.005; p = 0.005), TFP (p < 0.001; p < 0.001), AFP-L (p = 0.016; p = 0.015), LFP-R (p = 0.012; p = 0.009), and LFP-L (p < 0.001; p < 0.001). Taking the IVW random-effects model as gold standard, each standard deviation increment in genetically determined WC, BFP, TFP, AFP-R, AFP-L, LFP-R, and LFP-L raised the risk of AWH by 70.9%, 70.7%, 56.5%, 69.7%, 78.3%, 87.7%, and 72.5%, respectively. CONCLUSIONS: This study proves the causal relationship between AWH and BFD, attracting more attention from BMI to BFD. It provides evidence-based medical evidence that healthy figure management can prevent AWH.
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Estudio de Asociación del Genoma Completo , Hernia Ventral , Humanos , Análisis de la Aleatorización Mendeliana , alfa-Fetoproteínas , Herniorrafia , Distribución de la Grasa CorporalRESUMEN
PURPOSE: Incisional hernia (IH) is one of the most common complications after abdominal surgeries and may bring great suffering to patients. This study aims to evaluate the global trends in IH research from 2003 to 2023 and visualize the frontiers using bibliometric analysis. METHODS: The literature search was conducted on the Web of Science for IH studies published from 2003 to 2023 and sorted by citation frequency. The top 100 most-cited articles were analyzed by the annual publication number, prolific countries and institutions, influential author and journal, and the number of citations through descriptive statistics and visualization. RESULTS: The top paper was cited 1075 times and the median number of citations was 146. All studies were published between 2003 and 2019 and the most prolific year was 2003 with 14 articles. Jeekel J and Rosen M were regarded as the most productive authors with ten articles each and acquired 2738 and 2391 citations, respectively. The top three institutions with the most productive articles were Erasmus Mc, Carolinas Med Ctr, and Univ Utah, while the top three countries were the United States, Netherlands and Germany. The most frequent keyword was "incisional hernia" with 55 occurrences, followed by "mesh repair", "randomized controlled trial", and "polypropylene". CONCLUSION: The 100 most-cited papers related to IH were published predominantly by USA and European countries, with randomized controlled trial (RCT) and observational study designs, addressing topics related to risk factors, complications, mesh repair, and mesh components.
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Hernia Incisional , Humanos , Estados Unidos , Hernia Incisional/cirugía , Herniorrafia/efectos adversos , Bibliometría , Europa (Continente) , Alemania , Estudios Observacionales como AsuntoRESUMEN
PURPOSE: Incisional hernia (IH) is a common secondary ventral hernia after abdominal incisions and there is still little reliable evidence to predict and prevent IH. This study aimed to estimate risk factors of its incidence, especially concentrating on blood results. METHODS: 96 patients received midline laparotomy for gastrointestinal benign diseases and suffered from IH were enrolled in the IH group. A control group of 192 patients were randomly selected from patients underwent midline laparotomy for gastrointestinal benign diseases without IH. RESULTS: Patients in the IH group exhibited higher age (P < 0.001), BMI (P < 0.001), hernia history (P = 0.001) and laparotomy history (P < 0.001). Rate of coronary heart disease (P = 0.046), hypertension (P < 0.001), diabetes (P = 0.008), incisional infection (P = 0.004) and emergency surgery (P = 0.041) were also higher in the IH group. Patients with IH had lower levels of Hb (P = 0.002), TP (P = 0.013), ALB (P < 0.001), A/G (P = 0.019), PA (P < 0.001), HDL-C (P = 0.008) and ApoA1 (P = 0.005). Meanwhile, patients in the control group bore lower levels of LDH (P = 0.008), GLU (P = 0.007), BUN (P = 0.048), UA (P = 0.021), TG (P = 0.011), TG/HDL-C (P = 0.002), TC/HDL-C (P = 0.013), ApoB/ApoA1 (P = 0.001) and Lp(a) (P = 0.001). A multivariate logistic regression revealed that high BMI, laparotomy history, incisional infection, decreased PA, elevated levels of UA, Lp(a) and ApoB/ApoA1 were independent risk factors of IH. CONCLUSION: This is the first study to reveal the relationship between IH and serum biochemical levels, and give a prediction through the nomograph model. These results will help surgeons identify high-risk patients, and take measures to prevent IH during the perioperative period.
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Hernia Ventral , Hernia Incisional , Humanos , Hernia Incisional/epidemiología , Hernia Incisional/etiología , Hernia Incisional/cirugía , Herniorrafia/efectos adversos , Hernia Ventral/cirugía , Factores de Riesgo , Apolipoproteínas BRESUMEN
Perforation of digestive tract with intra-abdominal infection is one of the common causes of emergency surgery. After the resection with intestine, primary anastomosis or stoma remains a subject of debate. With the continuous improvement of surgical technology and the need to improve patients' quality of life, primary anastomosis is supposed to be the most ideal surgery. However, the rate of stoma is still high due to concerns about postoperative anastomotic leakage. This paper summarizes the surgical treatment of intra-abdominal infection caused by gastrointestinal perforation in recent years, and discuss the best operation plan according to the perforation location and etiology. We also discuss a variety of treatment methods for the prevention of anastomotic leakage (perioperative management, gastrointestinal anastomosis, enteric lavage decompression and other techniques) to improve the primary anastomosis, improve the quality of life of patients and reduce the medical burden.
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Fuga Anastomótica , Infecciones Intraabdominales , Humanos , Calidad de Vida , Tracto Gastrointestinal , Infecciones Intraabdominales/cirugía , Anastomosis QuirúrgicaRESUMEN
1. In this study, transcriptomics and metabolomics were used to analyse changes in gene expression and metabolites in the liver of 70-d-old mule ducks after 10 and 20 d of continuous overfeeding.2. In the free-feeding group, 995 differentially expressed genes and 51 metabolites (VIP >1, P < 0.05) were detected in the early stage, and 3,448 differentially expressed genes and 55 metabolites (VIP >1, P < 0.05) were detected in the later stage. There were 775 differentially expressed genes and 47 metabolites (VIP >1, P < 0.05) detected in the early stage of the overfeeding group, and 6,719 differentially expressed genes and 57 metabolites (VIP >1, P < 0.05) detected in the later stage.3. There were no significant differences between the early stage in the overfeeding and free-feeding groups at the transcriptional and metabolic levels. Oleic acid and palmitic acid synthesis increased in the early stage of the overfeeding and free-feeding groups, however, these were inhibited in the late stage. Fatty acid oxidation and ß-oxidation pathways were inhibited and insulin resistance was enhanced significantly in the late overfeeding stage.4. In the early stage, the digestion and absorption of fat in the overfeeding and free-feeding groups were enhanced. In the later stage, the ability to store triglyceride in the overfeeding group was greater than in the free-feeding group.5. The expression of nuclear factor κB (NFκB), a key inflammatory factor, was inhibited in the late stage of overfeeding, while arachidonic acid (AA), a metabolite with anti-inflammatory properties, increased in the late stage of overfeeding to inhibit the inflammatory effects caused by excessive lipid accumulation. These results add to the understanding of the mechanism of production of fatty liver in mule ducks and facilitate the development of treatments for non-alcoholic fatty liver disease.
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Patos , Metabolismo de los Lípidos , Animales , Metabolismo de los Lípidos/genética , Patos/genética , Patos/metabolismo , Transcriptoma , Pollos/genética , Hígado/metabolismoRESUMEN
To evaluate the safety of the domestic 13-valent pneumococcal polysaccharide conjugate vaccine-tetanus toxoid protein (PCV13-TT) after its licensure. The adverse event following immunization (AEFI) and the vaccination data of PCV13-TT in Zhejiang province from July 2020 to October 2021 were collected from national adverse event following immunization surveillance system and Zhejiang provincial immunization information system. Descriptive epidemiological method was used for this analysis. From July 2020 to October 2021, 302 317 doses of PCV13-TT were administered in children under 6 years old in Zhejiang Province and 636 AEFI case reports were received, with a reporting rate of 21.04 per 10 000 doses. Of these AEFI cases, 97.17% were mild vaccine product-related reaction (20.54 per 10 000 doses) and 95.44% occurred in the 0-1 d after vaccination (20.08 per 10 000 doses). The most common clinical diagnoses of AEFI included fever (224 cases), redness (204 cases), and induration (190 cases), while allergic rash (11 cases) was the most common diagnosis among the abnormal reactions. In conclusion,the present results bolstered that the domestic PCV13-TT was generally well tolerated in children under 6 years old in Zhejiang Province.
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Vacunas Neumococicas , Vacunación , Niño , Humanos , Preescolar , Vacunas Conjugadas/efectos adversos , Vacunas Neumococicas/efectos adversos , Inmunización , PolisacáridosRESUMEN
The understanding of the engrafted cell behaviors such as the survival, growth and distribution is the prerequisite to optimize cell therapy, and a multimodal imaging at both anatomical and molecular levels is designed to achieve this goal. We constructed a lentiviral vector carrying genes of ferritin heavy chain 1 (FTH1), near-infrared fluorescent protein (iRFP) and enhanced green fluorescent protein (egfp), and established the induced pluripotent stem cells (iPSCs) culture stably expressing these three reporter genes. These iPSCs showed green and near-infrared fluorescence as well as the iron uptake capacity in vitro. After transplanted the labeled iPSCs into the rat brain, the engrafted cells could be in vivo imaged using magnetic resonance imaging (MRI) and near-infrared fluorescent imaging (NIF) up to 60 days at the anatomical level. Moreover, these cells could be detected using EGFP immunostaining and Prussian blue stain at the cellular level. The developed approach provides a novel tool to study behaviors of the transplanted cells in a multi-modal way, which will be valuable for the effectiveness and safety evaluation of cell therapy.
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Células Madre Pluripotentes Inducidas , Animales , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Imagen Óptica , RatasRESUMEN
Background Aerobic glycolysis has a pivotal role in the carcinogenic process. The current understanding of the functional role and mechanism of UCHL3-related aerobic glycolysis in pancreatic cancer is far from comprehensive, therefore requires an in-depth analysis on this aspect. Methods In the present research, the expressions of ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), lactate dehydrogenase A (LDHA) and Forkhead box protein M1 (FOXM1) were detected by qRT-PCR, Western blot and immunohistochemistry. The effects of UCHL3 knockdown or overexpression on pancreatic cancer cells were examined by determining cell viability and colony formation. Aerobic glycolysis was assessed according to glucose uptake, lactic acid production, and lactate dehydrogenase (LDH) activity. Dual-luciferase reporter assay was performed to detect LDHA promoter activity. Results The results showed that UCHL3 expression was significantly increased in the pancreatic cancer tissues and cells, and that knocking down UCHL3 noticeably inhibited cell viability and aerobic glycolysis. Further investigations revealed that LDHA expression was promoted by UCHL3 and could be reduced by shFOXM1, and that low-expressed LDHA partly reversed the inhibition of aerobic glycolysis induced by overexpressed UCHL3. Conclusions To conclude, this study demonstrates that UCHL3 plays a carcinogenic role by promoting aerobic glycolysis in pancreatic cancer, suggesting that UCHL3 may be a potential diagnostic and therapeutic target for the treatment of cancer (AU)
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Humanos , Proteína Forkhead Box M1/metabolismo , Glucólisis/fisiología , L-Lactato Deshidrogenasa/metabolismo , Neoplasias Pancreáticas/metabolismo , Ubiquitina Tiolesterasa/fisiología , Regulación hacia Abajo , Línea Celular Tumoral , Proliferación Celular , Glucosa/metabolismo , AerobiosisRESUMEN
OBJECTIVE: To prepare Mn2+-doped Prussian blue nanoparticles (Mn-PB NPs) for T1-T2 dual-mode magnetic resonance imaging (MRI) and photothermal therapy in vitro. OBJECTIVE: Mn-PB NPs were prepared based on manganese chloride, ferrous chloride and potassium ferricyanide using the microemulsion method. The performance of T1-T2 dual-mode MRI with Mn-PB NPs and the photothermal property of the nanoparticles were assessed. CCK-8 assay and AM/PI double staining were used to evaluate the effect of photothermal therapy in vitro using the parepared nanoparticles. OBJECTIVE: The prepared Mn-PB NPs had a mean particle size of 39.46±0.42 nm with a Zeta potential of -25.9±1.2 mV and exhibited a good dispersibility and uniform particle size. In MRI using the nanoparticles, the r1 and r2 values reached 0.68 and 3.65 (mmol/L)-1s-1, respectively, indicating good performance of Mn-PB NPs for T1 and T2 enhancement in MRI. When irradiated with 808 nm laser for 10 min, Mn-PB NPs showed a temperature rise to 90 â to cause significant reduction of cell survival. CCK-8 assay and AM/PI double staining confirmed that Mn-PB NPs were capable of efficient killing of HepG2 cells upon 808 nm laser irradiation. OBJECTIVE: The Mn-PB NPs prepared in this work have uniform particle size and show good performances both in MRI for T1 and T2 enhancement and in photothermal therapy in vitro without obvious cytotoxicity.
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Nanopartículas , Terapia Fototérmica , Línea Celular Tumoral , Ferrocianuros , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVE: To evaluate the performance of 1H-magnetic resonance spectroscopy (1H-MRS), Dixon fat-water separation and Z-spectral magnetic resonance imaging (ZS-MRI) for quantification of fat content in phantoms and brown adipose tissues in rats. OBJECTIVE: First, six water-oil mixture phantoms with different fat fractions (0, 20%, 40%, 60%, 80% and 100%) were prepared and placed in a 50-mL centrifuge tube. ZS-MRI, 1H-MRS and Dixon's method were used to quantitatively evaluate the fat content of the phantom, and the results were compared against the actual fat fractions. Then, ZS-MRI and Dixon's method were used to collect the data in the interscapular region of 6 rats, the fat-water distribution map was calculated, and the results were compared with 1H-MRS. OBJECTIVE: ZS-MRI accurately quantified fat contents in the phantoms (Y=0.95*X+1.48). ZS-MRI was capable of distinguishing brown adipose tissue from white adipose tissue and defining the spatial distribution of the adipose tissue, and the results were highly consistent with those obtained by Dixon's method. No significant differences were found in the results derived by ZS-MRI and 1H-MRS for quantification of brown adipose tissue (P=0.35). OBJECTIVE: ZS-MRI can generate an artifact-free fat distribution map for quantitative measurement of the content and distribution of brown adipose tissues in rats.
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Tejido Adiposo Pardo , Agua , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo Pardo/diagnóstico por imagen , Animales , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Espectroscopía de Protones por Resonancia Magnética , RatasRESUMEN
BACKGROUND: Aerobic glycolysis has a pivotal role in the carcinogenic process. The current understanding of the functional role and mechanism of UCHL3-related aerobic glycolysis in pancreatic cancer is far from comprehensive, therefore requires an in-depth analysis on this aspect. METHODS: In the present research, the expressions of ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), lactate dehydrogenase A (LDHA) and Forkhead box protein M1 (FOXM1) were detected by qRT-PCR, Western blot and immunohistochemistry. The effects of UCHL3 knockdown or overexpression on pancreatic cancer cells were examined by determining cell viability and colony formation. Aerobic glycolysis was assessed according to glucose uptake, lactic acid production, and lactate dehydrogenase (LDH) activity. Dual-luciferase reporter assay was performed to detect LDHA promoter activity. RESULTS: The results showed that UCHL3 expression was significantly increased in the pancreatic cancer tissues and cells, and that knocking down UCHL3 noticeably inhibited cell viability and aerobic glycolysis. Further investigations revealed that LDHA expression was promoted by UCHL3 and could be reduced by shFOXM1, and that low-expressed LDHA partly reversed the inhibition of aerobic glycolysis induced by overexpressed UCHL3. CONCLUSIONS: To conclude, this study demonstrates that UCHL3 plays a carcinogenic role by promoting aerobic glycolysis in pancreatic cancer, suggesting that UCHL3 may be a potential diagnostic and therapeutic target for the treatment of cancer.
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Proteína Forkhead Box M1/metabolismo , Glucólisis/fisiología , Lactato Deshidrogenasa 5/metabolismo , Neoplasias Pancreáticas/metabolismo , Ubiquitina Tiolesterasa/fisiología , Regulación hacia Arriba , Aerobiosis , Línea Celular Tumoral , Proliferación Celular , Glucosa/metabolismo , Humanos , Páncreas/metabolismoRESUMEN
Objective: To investigate the diagnostic value of radiomics model based on plain CT scan of peripheral coronary artery adipose tissue for non-calcified plaque. Methods: The image data of 461 patients undergoing coronary CT angiography (CCTA) in the Department of Radiology of the First Affiliated Hospital of Suzhou University from August 1,2019 to July 31,2020 were retrospectively analyzed. Two hundred and six cases (355 branches) with non-calcified plaques, and 255 cases (510 branches) with no coronary artery disease were detected by CCTA. The regions of interest (ROI) of the pericoronary adipose tissue were segmented on the plain CT scan images (coronary calcification score (CCS) sequence). The coronary ROI was determined by selecting the coronary artery with a length of 40 mm and starting at 10 mm from the opening of the coronary artery, and the pericoronary adipose ROI was generated automatically. The pericoronary fat attenuation index (FAI) was then performed, and the radiomics features were extracted. The 865 coronary arteries were divided into the training group (n=606) and the testing group (n=259) at a ratio of 7â¶3, and the radiomics model was carried out. The receiver operating characteristic (ROC) analysis was used to assess the FAI value and the diagnostic efficacy of the radiomics model for non-calcified plaque. Results: A total of 1 692 features were extracted from images of pericoronary adipose based on plain scan. All features were screened by using max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), and 14 features were selected for the establishment of the radiomics model. The accuracy, sensitivity, specificity and area under the curve (AUC) of the model in distinguishing patients with non-calcified plaque and those without coronary stenosis in the testing group were 70.3%, 63.2%, 75.2% and 0.75, respectively. Conclusion: The radiomics model based on plain CT scan of the pericoronary adipose tissue had good diagnostic efficacy for non-calcified plaque.
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Placa Aterosclerótica , Tejido Adiposo/diagnóstico por imagen , Angiografía Coronaria , Estudios de Factibilidad , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Zero and low field nuclear magnetic resonance measurements have been performed on MAX phase samples (Cr1-x Mn x )2AC with A = Ge and Ga in order to obtain local microscopic information on the nature of magnetism in this system. Our results unambiguously provide evidence for the existence of long-range magnetic order in (Cr0.96Mn0.04)2GeC and for (Cr0.93Mn0.07)2GaC, but not for (Cr0.97Mn0.03)2GaC. We point to a possible dependence of long range magnetic order in these MAX phase compounds on the A atom.
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OBJECTIVE: LINC00240, as a novel long non-coding RNAs (lncRNAs), has never been studied in hepatocellular carcinoma (HCC). This research reported the expression and function of LINC00240 in HCC. PATIENTS AND METHODS: LINC00240 expression in 180 HCC patients was downloaded from the Cancer Genome Atlas (TCGA) database. HCC patients' survival was analyzed via KaplanMeier analysis. The expression of LINC00240, miR-4465 and HGF in Hep3B and Huh7 cells were regulated by transfection. Cell viability was determined by MTT assay. Transwell experiment was used for the detection of cells migration and invasion abilities. The interaction between LINC00240, miR-4465 and HGF was reflected by Luciferase reporter assay. LINC00240, miR-4465, HGF and p-c-MET expression in HCC cells were researched by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. RESULTS: TCGA data showed that high LINC00240 expression was markedly associated with lower survival of HCC patients (p = 0.036). LINC00240 expression was aberrantly upregulated in HCC cells. Silencing of LINC00240 significantly reduced HCC cells viability, migration and invasion. miR-4465 was a target gene of LINC00240. Silencing of LINC00240 reduced HCC cells viability, migration and invasion via directly promoting miR-4465 expression. HGF was target gene of miR-4465. miR-4465 up-regulation obviously suppressed HGF and p-c-MET expression. According to rescue experiment, LINC00240 silencing inhibited HCC cells viability, migration and invasion by suppressing HGF/c-MET signaling pathway via targeting miR-4465. CONCLUSIONS: LINC00240 sponges miR-4465 to promote HCC cells proliferation, migration and invasion via HGF/c-MET signaling pathway.
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Carcinoma Hepatocelular/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , ARN Largo no Codificante/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Factor de Crecimiento de Hepatocito/genética , Humanos , Neoplasias Hepáticas/patología , MicroARNs/genética , Proteínas Proto-Oncogénicas c-met/genética , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
Extracellular vesicles (EVs) are small lipid-encapsulated vesicles secreted from specific cells that can be taken up by other cells, thereby allowing for the efficient transport of macromolecules such as lipids, proteins, and nucleic acids between tissues and organs in vivo. These EVs have been found to play critical roles in normal tissue homeostasis and disease development, serving to regulate complex processes, including inflammation, immunity, and angiogenesis. At present, the leading global cause of the end-stage renal disease (ESRD) is diabetic kidney disease (DKD), with the prevalence of this latter condition being predicted to increase in the near future due to rising type 2 diabetes mellitus (T2DM) incidence. Recent work from several research groups has highlighted a potential role for EVs in the development of DKD. The present review, therefore, serves to explore the relevance of EVs to the development, detection, and treatment of DKD in an effort to better understand this complex disease state.
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Nefropatías Diabéticas/metabolismo , Vesículas Extracelulares/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/tratamiento farmacológico , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/metabolismoRESUMEN
B-Lymphoblastic leukemia (B-LL) is the most common childhood hematological malignancy. Although its overall prognosis is good, the outcome after relapse is poor. CD19 is highly expressed on the membrane of most malignant B-cells, and was shown to be a promising therapeutic target of B-LL. In this present work, we designed and synthesized a novel drug carrier, anti-CD19 monoclonal antibody-conjugated human serum albumin nanoparticles (HSA-CD19 NPs). Doxorubicin (DOX) was well encapsulated into the HSA-CD19 NPs to form an anticancer nanodrug DOX/HSA-CD19. DOX/HSA-CD19 was preferentially uptaken by CD19+ B-LL cell line KOPN-8. DOX/HSA-CD19 showed strong antiproliferative effect on KOPN-8 cells with an IC50 value of 4.1 µg/mL. Further, proapoptotic Bax and caspase-3 were significantly elevated, but antiapoptotic Bcl2 was reduced in DOX/HSA-CD19 treated KOPN-8 cells, indicating the activation of the apoptosis pathway by the nanodrug. By contrast, DOX/HSA-CD19 did not show affinity to CD19-monocytic cell line, U937, and did not affect its proliferation. Collectively, HSA-CD19 NPs are a kind of effective novel drug carrier, and DOX/HSA-CD19 is a promising antitumor nanodrug for the treatment of B-LL.
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Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacología , Anticuerpos Monoclonales/inmunología , Antígenos CD19/inmunología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/farmacología , Portadores de Fármacos/química , Humanos , Concentración 50 Inhibidora , Nanopartículas , Albúmina Sérica Humana/químicaRESUMEN
Objective: To explore the possible role of Irisin in antipsychotic drug-induced insulin resistance and abdominal obesity in patients with schizophrenia and to provide a theoretical basis for the prevention of antipsychotic drug-induced obesity. Methods: Fifty-five patients with first-episode schizophrenia, from the First Affiliated Hospital of Zhengzhou University, between January 2016 and December 2017, were admitted as well as fifty healthy controls during the same period. Serum Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), total cholesterol (TCHO), highdensity lipoprotein (HDL), low density lipoprotein (LDL) were detected. Results: The average Irisin level ((233±228) mmol/L) was higher than that in the normal control group ((124±89) mmol/L) (P<0.05).Repeated measurement analysis of variance showed that the average levels of the height, waist, FBG, INS, TCHO, TG, HDL, LDL, BMI, HOMA-IR and Irisin at the end of the 12(th) and 24(th) week's treatment were higher than baseline (P<0.05). After correlation analysis, the level of Irisinat baseline was positively correlated with HOMA-IR (r=0.383, P<0.05). At the 12(th) week, the level of Irisin was positively correlated with waist circumference, and HOMA-IR (r=0.360, r=0.475, all P<0.05). Multiple linear regression analysis showed that at the 12(th) week's treatment, compared with the baseline period, changes of Irisin was positively correlated with waist circumference and HOMA-IR, respectively (ß=0.453, ß=0.420, both P<0.05). Conclusion: Irisin may be involved in the process of metabolic regulation and bean early predictor of antipsychotic drug-induced insulin resistance and abdominal obesity.