RESUMO
Objective: To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) . Methods: In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 µmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 µmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 µmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 µmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 µmol/L PQ), and inhibitor group (200 µmol/L PQ+20 µmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted. Results: The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance (P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group (P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group (P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group (P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group (P<0.05/3) . Conclusion: CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.
Assuntos
Fator de Crescimento do Tecido Conjuntivo , Transição Epitelial-Mesenquimal , Paraquat , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Paraquat/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Ratos , Linhagem Celular , Morfolinas/farmacologia , Cromonas/farmacologia , Caderinas/metabolismoRESUMO
Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (tâ =-2.940, P=0.004), aspartate aminotransferase (tâ =-2.749, P=0.007), ALT (tâ =-2.153, P=0.033), HBV DNA level (tâ =-4.771, P=0.010) and portal vein inner diameter (tâ =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.
Assuntos
Alanina Transaminase , Antígenos E da Hepatite B , Vírus da Hepatite B , Fígado , Humanos , Fígado/patologia , Alanina Transaminase/sangue , Antígenos E da Hepatite B/sangue , Inflamação , DNA Viral , Masculino , Hepatite B Crônica/patologia , Feminino , Modelos Logísticos , Curva ROC , Veia Porta , Hepatite B , gama-Glutamiltransferase/sangue , AdultoRESUMO
Objective: The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation. Methods: We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation. Results: A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence. Conclusion: Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.
Assuntos
Mesentério , Anormalidade Torcional , Humanos , Mesentério/cirurgia , Anormalidade Torcional/cirurgia , Resultado do Tratamento , Laparotomia , Recidiva , Masculino , Feminino , Pessoa de Meia-Idade , AdultoRESUMO
Objective: To summarize the characteristics of multisystem deformities in patients with Klippel-Feil syndrome (KFS) combined with congenital scoliosis (CS). Methods: Within the framework of the "Deciphering Disorders Involving Scoliosis and Comorbidities (DISCO)" research collaboration, a retrospective analysis was conducted on patients diagnosed with KFS and CS at Peking Union Medical College Hospital between April 2005 and August 2022. Patient data, including imaging examinations and medical records, were collected to summarize the spinal and associated deformities. Results: A total of 82 KFS patients with concurrent CS were included, comprising 42 males and 40 females. The average age was (12.8±8.9) years. Among the KFS patients, there were 31 cases of Type â , 12 cases of Type â ¡, and 39 cases of Type â ¢. The most common location for the major curve of scoliosis was the mid-thoracic segment (42 cases, 51.2%). Hemivertebrae deformities were most frequently observed in the upper thoracic segment (31 cases, 60.8%). There were no statistically significant differences in age, gender, major curve Cobb angle, or region of hemivertebrae occurrence among the different types of KFS (all P>0.05). Apart from spinal vertebral deformities, intraspinal deformities had the highest comorbidity rate (33 cases, 40.2%). The subjects were divided into two groups based on the presence or absence of intraspinal deformity (absence as group G0, presence as group G1), there was a statistically significant difference in the main Cobb angle [M(Q1, Q3)] between the two groups, which was 45.0° (27.5°, 62.0°) and 60.0° (37.5°, 83.5°), respectively (P=0.044). Additionally, a portion of the patients had concurrent cardiovascular system abnormalities (13 cases, 15.9%), craniofacial-ocular-auricular abnormalities (8 cases, 9.8%), genitourinary system abnormalities (7 cases, 8.5%), and gastrointestinal abnormalities (2 cases, 2.4%). Conclusions: Patients with KFS combined with CS commonly present with a major curve of spinal deformity in the mid-thoracic segment and often have comorbidities involving multiple systems. When combined with intraspinal anomalies, the major curve exhibits a greater degree of curvature.
Assuntos
Síndrome de Klippel-Feil , Escoliose , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Síndrome de Klippel-Feil/epidemiologia , Estudos Retrospectivos , Coluna Vertebral , Exame FísicoRESUMO
Feed efficiency is a highly important economic trait in sheep production and has a significant impact on the economic benefits of sheep farming. Microbial fermentation of the rumen has a vital role in the host's nutrition; the rumen microbiota might affect host feed efficiency. However, the relationship between the rumen microbiota and feed efficiency in sheep is unclear. In the present study, the microbiota of 195 Hu sheep was investigated and their residual feed intake (RFI), a commonly used measure of feed efficiency, was determined. From birth, all sheep were subjected to the same management practices. At slaughter, samples of liquid rumen contents were collected and subjected to amplicon sequencing for the 16S rDNA gene on the IonS5™XL platform. To identify the bacterial taxa differentially represented at the genus or higher taxonomy levels, we used linear discriminant analysis coupled with effect size and curve fitting. In the sheep rumen, the four most abundant phyla were Firmicutes, Bacteroidetes, Fibrobacteres, and Proteobacteria; and the dominant genera were unidentified Prevotellaceae, Fibrobacter, unidentified Lachnospiraceae, Saccharofermentans, and Succinivibrio. Pathway analysis of the 16S rDNA sequencing data from the rumen microbiota identified that carbohydrate metabolism was enriched. Using α-diversity analysis, we further identified that Observed species, ACE, Good's coverage, and Chao1 are more abundant (Pâ¯<â¯0.01) in the low-RFI (L-RFI) group compared to the high-RFI (H-RFI) group. High-RFI sheep had a higher abundance of three bacterial taxa (Prevotellaceae, Negativicutes, and Selenomonadales), and one taxa was overrepresented in the L-RFI sheep (Succinivibrio), respectively. Furthermore, model fitting showed that Veillonellaceae, Sphaerochaeta, Negativibacillus, Saccharofermentans, and members of the Tenericutes, Kiritimatiellaeota, Deltaproteobacteria, and Campylobacterales were correlated with the sheep RFI classification and thus were indicative of a role in animal efficiency. Tax4Fun analysis revealed that metabolic pathways such as "energy metabolism," "metabolism of cofactors and vitamins," "poorly characterized," and "replication recombination and repair proteins" were enriched in the rumen from H-RFI sheep, and "genetic information processing" and "lipopolysaccharide biosynthesis" were overrepresented in L-RFI sheep rumen. In addition, six Kyoto Encyclopedia of Genes and Genomes orthology pathways were identified as different between H-RFI and L-RFI groups. In conclusion, the low RFI phenotype (efficient animals) consistently (or characteristically) exhibited a more abundant and diverse microbiome in sheep.
Assuntos
Microbiota , Rúmen , Ração Animal/análise , Animais , Bactérias/genética , Ingestão de Alimentos , OvinosRESUMO
Long noncoding RNAs (LncRNAs), as key regulators, have vital functions in various biological activities. However, in sheep, little has been reported concerning the genetic mechanism of LncRNA regulation of feed efficiency. In the present study, we explored the genome-wide expression of LncRNAs and transcripts of uncertain coding potential (TUCPs) in the livers of sheep with extreme residual feed intake (RFI) using RNA sequencing. We identified 1 523 TUCPs and 1 996 LncRNAs, among which 10 LncRNAs and 16 TUCPs were identified as being differentially expressed between the High-RFI and Low-RFI groups. Co-expression and co-localization methods were used to search for LncRNA and TUCP target genes, which identified 970/1 538 and 23/27 genes, respectively. Ontology and pathways analysis revealed that the LncRNAs/TUCPs that were highly expressed in the Low-RFI group are mostly concentrated in energy metabolism pathways. For example, LNC_000890 and TUCP_000582 might regulate liver tissue metabolic efficiency. The LncRNAs/TUCPs that were highly expressed in the High-RFI group are mostly enriched in immune function pathways. For example, TUCP_000832 might regulate animal health, thereby affecting feed efficiency. Subsequently, a co-expression network was established by applying the expression information of both the differentially expressed LncRNAs and TUCPs and their target mRNAs. The network indicated that differentially expressed genes targeted by the upregulated LncRNAs and TUCPs were mainly related to energy metabolism, while those genes targeted by the downregulated LncRNAs and TUCPs were mainly related to immune response. These results provide the basis for further study of LncRNA/TUCP-mediated regulation of feed efficiency.
Assuntos
RNA Longo não Codificante , Animais , Ingestão de Alimentos , Perfilação da Expressão Gênica/veterinária , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro , Ovinos/genética , TranscriptomaRESUMO
The effect of Ageratina adenophora on pathological characteristics of the liver and lungs as well as serum biochemical parameters in horses were investigated. Ten horses without ingestion history of Ageratina adenophora were classified into the control group, and 10 poisoned but survived horses with 3 months ingestion history were set as the case group. Results showed that serum AST, ALT, ALP, magnesium and phosphorus were elevated significantly, while creatinine was decreased remarkably. Hematoxylin and eosin staining of liver tissues showed diffuse swelling or destruction of hepatocytes, narrowing or atrophy of the hepatic sinusoids, and little lymphocytic infiltration; lung tissues presented destroyed alveoli and inflammatory cell infiltration.
Assuntos
Ageratina , Animais , Hepatócitos , Cavalos , FígadoRESUMO
Objective: To investigate the impact of heterotopic ossification (HO) after cervical disc replacement (CDR) on clinical outcome and radiological outcome of adjacent segment. Methods: The data of patients underwent single-level Prestige-LP CDR between January 2008 and March 2014 in West China Hospital with a minimum 36 months of follow-up were retrospectively analyzed in this study. The incidence of HO, whether it affected clinical outcome, and its impact on adjacent segment intervertebral disc height (IDH), range of motion (ROM) and adjacent segment degeneration were observed. The data were compared with independent sample t test between the two groups. Results: Ninety-two patients were included in this study, including 48 males and 44 females, the mean age was (44±8) years, and the mean follow-up was (62±23) months. At the final follow-up, 34 patients developed HO after CDR, but the incidence of Grade 4 HO was 7.6%. In both of the HO and non-HO groups, clinical outcomes at the final follow-up were all significantly improved when compared to those before the operation. And there was no significant differences in any clinical indexes between the HO and non-HO groups. The adjacent segment IDH before operation and at the final follow-up in the HO group and non-HO group were similar(t=0.596, 0.825 and t=0.877, 0.644, all P>0.05). The preoperative adjacent segment ROM of HO group was similar with that in non-HO group(t=0.056, 0.709, both P>0.05), but the adjacent segment ROM in HO group was higher than that in the non-HO group at the final follow-up (upper adjacent segment: 10.0°±2.0° vs 9.0°±1.3°; lower adjacent segment: 10.2°±1.9° vs 8.8°±1.3°, t=2.824, 4.022, both P<0.05). The incidence of adjacent segment degeneration of HO group was higher than that of non-HO group at the final follow-up(41.2% vs 19.0%, χ(2)=5.343, P<0.05). Conclusions: HO is a common phenomenon in the long-term follow-up after the CDR operation with Prestige LP prosthesis, but HO does not affect the improvement of clinical outcome. HO after CDR might be one of important risk factors accelerating adjacent segment degeneration.
Assuntos
Disco Intervertebral , Ossificação Heterotópica , Adulto , Vértebras Cervicais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the influences of micro ribonucleic acid (miR)-181b on the inflammation and vascular endothelial function in atherosclerosis (AS), and its specific molecular regulatory mechanism. MATERIALS AND METHODS: 44 apolipoprotein E (ApoE)-/- 7 weeks old male rats were randomly divided into normal diet group (NC group) and AS model group (high-fat diet feeding). Rat aorta was dissected and the serum sample was collected in both groups. The serum levels of inflammatory factors in both groups were detected via enzyme-linked immunosorbent assay (ELISA). The mRNA levels of miR-18b and Notch1 were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Moreover, aortic endothelial cells were extracted from AS rats. The mir-18b binding target gene was analyzed via bioinformatics and further verified by the Luciferase reporter gene assay. The protein expressions of miR-18b and Notch1 in endothelial cells transfected with miR-181b mimic or inhibitor were detected. Influence of miR-181b on vascular endothelial indexes was also detected. RESULTS: Compared with those in the NC group, the serum levels of interleukin-6 (IL-6), IL-10, IL-13 and tumor necrosis factor-α (TNF-α) in the AS group significantly increased (p<0.05). The mRNA level of miR-18b in AS plaques was significantly lower than that in NC arterial tissues. Conversely, Notch1 level in AS plaques was markedly higher than that in the NC arterial tissues (p<0.05), with the mean difference of 2.12 and 2.82 folds (p<0.05). According to the Pearson correlation analysis, there was a significant negative correlation between mRNA levels of miR-181b and Notch1 in AS tissues (r=-0.65, p=0.014). The bioinformatics analysis showed that there were complementary binding sites between miR-181b and Notch1. The Luciferase reporter gene assay confirmed the presence of direct binding sites between miR-181b and Notch1. Western blotting revealed that the overexpression of miR-181b downregulated Notch1 and hs-CRP, but upregulated BNP (p<0.05). Opposite trends were obtained by miR-181b knockdown (p<0.05). CONCLUSIONS: The decline in the miR-181b expression may be an important factor in AS plaque formation and vascular endothelial injury by regulating Notch1.
Assuntos
Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , MicroRNAs/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais/fisiologia , Animais , Aterosclerose/patologia , Endotélio Vascular/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Ligação Proteica/fisiologia , Ratos , Ratos TransgênicosRESUMO
OBJECTIVE: To explore the effects and mechanism of action of micro ribonucleic acid (miR)-21 on the proliferation and migration of vascular smooth muscle (VSM) in atherosclerosis (AS). MATERIALS AND METHODS: The rats were fed with a high-fat diet, and the oil red staining was adopted to compare AS between Sprague Dawley (SD) rats and miR-21 knockdown rats. At the in-vitro level, primary rat VSM cells (VSMCs) were selected and divided into miR-NC blank control group [miR-normal control (NC) group] and miR-21 overexpression group (miR-21 group) for relevant experimental detection. Wound healing assay and transwell assay were used to detect the effects of miR-21 on the proliferation and migration of VSMCs. Westernn blotting was applied to examine the changes in the levels of Cyclin D, a cell cycle-related protein, and the key factors of the Akt/ERK signaling pathway, such as phosphorylated-Akt (p-AKT), AKT, p-ERK1/2, and ERK1/2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell activity assay kit was applied to determine the effects of miR-21 on the proliferation of VSMCs through regulating the Akt/ERK signaling pathway after the ERK signaling pathway inhibitor PD98059 and AKT inhibitor MK-2206 were given. RESULTS: Compared with that in miR-NC group, the level of AS in miR-21 knockdown rats were decreased significantly (p < 0.05). In the cell-level experiment, the overexpression of miR-21 promoted abnormal proliferation of VSMCs and activated the Akt/ERK signaling pathway (p < 0.05). MTT assay results revealed that inhibiting the Akt/ERK pathway could reverse the effects of miR-21 promoting proliferation and migration. CONCLUSIONS: MiR-21 promotes the proliferation and migration of VSMCs by activating the Akt/ERK pathway and aggravates AS. Knocking down miR-21 or inhibiting the Akt/ERK pathway can suppress the activation of VSMCs.
Assuntos
Aterosclerose/genética , Dieta Hiperlipídica/efeitos adversos , MicroRNAs/genética , Músculo Liso Vascular/citologia , Animais , Aterosclerose/induzido quimicamente , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Flavonoides/farmacologia , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Compostos Heterocíclicos com 3 Anéis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Objective: To investigate the incidence rate of transjugular intrahepatic portosystemic shunt (TIPS) complications in the treatment of cirrhotic portal hypertension, and analyze the cause of complication to management methods. Methods: Data of 116 patients obtained from Zhongnan Hospital of Wuhan University were retrospectively analyzed. Portal venous pressure, routine blood test, coagulation test, liver and kidney function test, ammonia blood test, imaging and endoscopy reports were collected before and after procedure. The incidence rate of hepatic encephalopathy, gastrointestinal bleeding, ascites and shunt dysfunctions were observed. Data were expressed as mean ± Standard deviation and analyzed by t-test. A chi-squared test was used for comparison between categorical variables. Results: The success rate of TIPS operation was 97.41% (113/116). Two patients underwent prompt TIPS procedure due to active bleeding. Bleeding was successfully stopped. Portal venous pressure of 113 patients decreased from (42.73 ± 7.64) cmH(2)O to (24.92 ± 7.60) cmH(2)O, and the difference was statistically significant (P < 0.01). Twenty cases were of hepatic encephalopathy. Preoperative level of Child-pugh class C patients was more susceptible to hepatic encephalopathy within 3 months after procedure than class A and B. After TIPS procedure, there were 22 cases of gastrointestinal bleeding, 18 cases of shunt dysfunctions and 26 cases of disease related death. Conclusion: Rational patient selection strategies can effectively reduce portal venous pressure, incidence of hepatic encephalopathy, improve mid-and long-term therapeutic effects, and provide opportunities for liver transplantation.
Assuntos
Hipertensão Portal/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Criança , Varizes Esofágicas e Gástricas/epidemiologia , Seguimentos , Hemorragia Gastrointestinal/epidemiologia , Encefalopatia Hepática/epidemiologia , Humanos , Hipertensão Portal/diagnóstico , Incidência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The pathogenesis of vascular dementia (VD) is not fully elucidated. Th1/Th2 balance may change in VD, leading to numerous inflammatory cytokines secretion. Interleukin-10 (IL-10) is an immune suppressor, while its function in VD and correlation with Th1/Th2 balance are still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided into three groups, including sham group, model group, and IL-10 group. Th1 and Th2 cytokines IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α) expressions in the serum were tested by enzyme-linked immunosorbent assay (ELISA). IL-10 expression in brain tissue and peripheral blood was detected by Real-Time PCR and ELISA. The correlation relationship between IL-10 and T helper cells 1/2 (Th1/Th2) cytokines was analyzed. Hippocampus cell apoptosis was determined by caspase 3 activity kit. Nuclear transcription factor 2 κB (NF-κB) expression was evaluated by Western blot. RESULTS: IL-10 levels were decreased, caspase 3 activity was enhanced, NF-κB expression was declined, IL-2 and TNF-α secretion were up-regulated, while IL-4 and IL-6 secretion were reduced in hippocampus tissue and peripheral blood from VD model rat compared to sham group (p<0.05). IL-10 significantly attenuated caspase 3 activity, up-regulated NF-κB expression, reduced IL-2 and TNF-α secretion, and enhanced IL-4 and IL-6 secretion (p<0.05). IL-10 was negatively correlated with Th1 cytokines and positively correlated with Th2 cytokines (p<0.05). CONCLUSIONS: IL-10 expression declined in VD and participated in regulating Th1/Th2 balance. IL-10 participated in VD incidence and development through regulating cell apoptosis and NF-κB expression.
Assuntos
Demência Vascular/imunologia , Interleucina-10/fisiologia , Equilíbrio Th1-Th2 , Animais , Citocinas/sangue , Demência Vascular/etiologia , Masculino , NF-kappa B/fisiologia , Ratos , Ratos WistarRESUMO
Objective: To investigate the prognostic factors related to the severity of acute pancreatitis and to establish the multiple predictor models of severe acute pancreatitis(SAP) in elderly patients. Methods: Clinical data of 146 consecutive elderly patients who met the inclusion criteria between January 2014 and May 2017 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University were retrospectively collected and analyzed, wherein 88 cases were mild acute pancreatitis, 29 cases were moderately severe acute pancreatitis and 29 cases were SAP. The patients data were subjected to univariate analysis and multiple classified Logistic regression analysis for independent prognostic factors of the severity of acute pancreatitis in elderly patients. Unweighted predictive score(unwScore) and weighted predictive score(wScore)for SAP in elderly patients were established according which the receiver-operating characteristic(ROC) curves of independent prognostic factors and predictor models were produced. The cutoff values of independeut prognostic factors and predictor models were determined. The area under the curve, the sensitivity, the specificity, the positive predictive value and the negative predictive value to verify the predictive efficiency of the independent prognostic factors and predictor models were calculated. Results: Procalcitonin(PCT)(Z=10.564, P=0.000), blood urea nitrogen(BUN)(Z=22.231, P=0.003), serum creatinine(Scr)(Z=14.151, P=0.030), serum calcium(Z=34.979, P=0.032) and pleural effusion(χ(2)=28.463, P=0.015) were independent prognostic factors of the severity of acute pancreatitis by univariate analysis and multiple classified Logistic regression analysis in elderly patients. Respectively, the area under the curve of PCT, BUN, Scr, serum calcium and pleural effusion were 0.908, 0.737, 0.701, 0.753, 0.712, the sensitivity were 0.828, 0.621, 0.552, 0.690, 0.517, the specificity were 0.915, 0.786, 0.846, 0.966, 0.906, the positive predictive value were 70.6%, 41.9%, 47.1%, 83.3%, 57.7%, the negative predictive value were 95.5%, 89.3%, 88.4%, 92.6%, 88.3%. Respectively, the area under the curve of unwScore and wScore were 0.915 and 0.953, the sensitivity were 0.759 and 0.931, the specificity were 0.889 and 0.915, the positive predictive value were 62.9% and 73.0%, the negative predictive value were 93.7% and 98.2%. Conclusions: PCT, BUN, Scr, serum calcium and pleural effusion were independent prognostic factors of the severity of acute pancreatitis in elderly patients. The multiple predictor models of SAP in elderly patients have a good predictive efficiency, which may provide valuable clinical reference for prediction and treatment.
Assuntos
Pancreatite , Doença Aguda , Idoso , Biomarcadores , Humanos , Pancreatite/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Peroxiredoxin1 (PRDX1), a class of thiol peroxidases, is a multifunctional protein. We aimed at analyzing the effect of PRDX1 on proliferation, apoptosis, migration and invasion of colorectal cancer and to investigate the potential mechanism. MATERIALS AND METHODS: Western blot and PCR were used to validate the silencing efficiency in SW480 cell by transfection of PRDX1-siRNA. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) test. Flow cytometry Annexin V/PI double staining was used to analyze cell apoptosis. Transwell and scratch test were used to detect the migration and invasion of cells. Signal pathway protein expression was analyzed by Western blot. RESULTS: The expression of PRDX1 in SW480 cells could be reduced by siRNA effectively. The cell proliferation, migration and invasion were reduced significantly compared with control group after down-regulation of PRDX1 (p<0.05), while the cell apoptosis was enhanced significantly (p<0.05). The ratio of phospho-p38 mitogen-activated protein kinases (p-p38) /p38 mitogen-activated protein kinases (p38) was down-regulated after the down-regulation of PRDX1 (p<0.05). The ratio of phospho-c-Jun N-terminal protein kinase (p-JNK)/c-Jun N-terminal protein kinase (JNK) and phospho-extracellular regulated protein kinases (p-ERK)/extracellular regulated protein kinases (ERK) showed changes with no significant difference (p>0.05). CONCLUSIONS: Down-regulation of PRDX1 in colorectal cancer SW480 cells could inhibit the cell proliferation, migration, invasion, and induce cell apoptosis. This is very likely to be achieved by activating the p38MAPK-signaling pathway.
Assuntos
Neoplasias Colorretais/patologia , Peroxirredoxinas/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade NeoplásicaRESUMO
BACKGROUND: Although cytoreductive surgery has been shown to be beneficial in carefully selected patients with metastatic gastrointestinal stromal tumours (GISTs) treated with tyrosine kinase inhibitors (TKIs), factors predictive of postoperative morbidity have not been investigated previously. METHODS: A surgical complexity score for GIST metastasectomy (GM-SCS) composed of patient-related and surgical factors was assigned retrospectively to patients with metastatic GIST treated with TKI therapy and surgery at two institutions between 2002 and 2014. The ability of clinicopathological factors and GM-SCS to predict postoperative morbidity was assessed by means of a multivariable logistic regression model. Postoperative complications were categorized using the Clavien-Dindo classification. RESULTS: Some 400 operations on 323 patients with metastatic GIST on TKIs were included. Complications were observed following 110 operations (27·5 per cent) including 70 major complications (grade III-V) (17·5 per cent of 400 operations). Patients were divided into low (5 points or less; 100 patients, 25·0 per cent), intermediate (6-9 points; 191, 47·8 per cent) and high (at least 10 points; 109, 27·3 per cent) complexity scoring groups based on the GM-SCS. An intermediate (odds ratio (OR) 2·88; P = 0·008) and high (OR 5·40; P < 0·001) GM-SCS were independent predictors of overall complications, whereas only a high GM-SCS was independently predictive of a major complication (OR 3·65; P = 0·018). Metastatic mitotic index was also an independent predictor of overall complications (OR 2·55; P = 0·047). GM-SCS did not predict progression-free or overall survival. CONCLUSION: A gastrointestinal stromal tumour metastastectomy surgical complexity score can predict morbidity, which may help in preoperative risk stratification and optimal treatment planning.
Assuntos
Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Mesilato de Imatinib/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Idoso , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/terapia , Humanos , Metastasectomia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The objective of this study was to evaluate the effect of residual feed intake (RFI) on rumen function in finishing lambs. A total of 60 male Hu lambs (average initial BW = 25.2 ± 2.5kg) were used and were offered a pelleted high-concentrate diet, of which the forage to concentrate ratio was 25:75. Individual feed intake was recorded over a period of 42 d, then 10 lambs with the lowest RFI and the highest RFI were selected, respectively. The rumen fluid used for fermentation variables and relative abundance of bacteria measurement was obtained on d 10 and 20 after RFI measurement. At the end of this experiment, the selected lambs were slaughtered and rumen epithelium and liver tissues were collected for RNA extraction. Low-RFI lambs had lower ( < 0.01) DMI and greater ( < 0.05) G:F than the high-RFI ones, while the RFI groups did not differ in ADG and BW ( > 0.05). Additionally, RFI was positively ( = 0.57; < 0.01) correlated with DMI and negatively ( = -0.53; < 0.05) correlated with G:F. Total VFA and individual VFA decreased ( < 0.05) over time. The concentrations of total VFA, acetate, valerate, isobutyrate, isovalerate, and rumen pH ( > 0.05) were not affected by RFI classification. Nonetheless, low-RFI group lambs had a greater ( < 0.05) concentration of propionate, a lower ( < 0.05) concentration of butyrate, and a lower ( < 0.05) acetate to propionate ratio compared with the high-RFI group. There was a significant ( < 0.05) effect of RFI on the relative abundance of and . The relative abundance of , , and decreased ( < 0.05) over time in high-RFI group. And the relative abundance of in high-RFI group was greater ( < 0.05) than its low-RFI counterpart. Furthermore, RFI had no effect ( > 0.05) on gene expression associated with intracellular pH regulation (, , , , , , , and ) in rumen epithelium and ß-hydroxybutyrate metabolism () in both rumen epithelium and liver tissues. In conclusion, even though low-RFI lambs had lower DMI, however, the number of was lower. Additionally, there was no difference in gene expressions level associated with intracellular pH regulation in rumen epithelium between RFI groups.
Assuntos
Comportamento Alimentar/fisiologia , Rúmen/fisiologia , Ovinos/fisiologia , Ácido 3-Hidroxibutírico , Ração Animal/análise , Animais , Bactérias , Dieta/veterinária , Epitélio/fisiologia , Fermentação , Regulação da Expressão Gênica/fisiologia , Concentração de Íons de Hidrogênio , Masculino , FenótipoRESUMO
SiO2@Y2MoO6:Eu3+ core-shell phosphors were prepared by the sol-gel process. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectra (EDS), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as kinetic decays were used to characterize the resulting SiO2@Y2MoO6:Eu3+ core-shell phosphors. The XRD results demonstrated that the Y2MoO6:Eu3+ layers on the SiO2 spheres crystallized after being annealed at 700 °C and the crystallinity increased with raising the annealing temperature. The obtained core-shell phosphors have spherical shape with narrow size distribution (average size ca. 640 nm), non-agglomeration, and smooth surface. The thickness of the Y2MoO6:Eu3+ shells on the SiO2 cores could be easily tailored by varying the number of deposition cycles (70 nm for four deposition cycles). The Eul+ shows a strong PL emission (dominated by 5D0-7F2 red emission at 614 nm) under the excitation of 347 nm UV light. The PL intensity of Eu3+ increases with increasing the annealing temperature and the number of coating cycles.
RESUMO
High quality, c-axis oriented, MgB2 thin films were successfully grown on 6H-SiC substrates using pulsed laser deposition (PLD) with subsequent in situ annealing. To obtain high purity films free from oxygen contamination, a dense Mg-B target was specially made from a high temperature, high pressure reaction of Mg and B to form large-grained (10~50 µm) MgB2. Microstructural analysis via electron microscopy found that the resulting grains of the film were composed of ultrafine columnar grains of 19-30 nm. XRD analysis showed the MgB2 films to be c-axis oriented; the a-axis and c-axis lattice parameters were determined to be 3.073 ± 0.005 Å and 3.528 ± 0.010 Å, respectively. The superconducting critical temperature, Tc,onset , increased monotonically as the annealing temperature was increased, varying from 25.2 K to 33.7 K. The superconducting critical current density as determined from magnetic measurements, Jcm , at 5 K, was 105 A/cm2 at 7.8 T; at 20 K, 105 A/cm2 was reached at 3.1 T. The transport and pinning properties of these films were compared to "powder-in-tube" (PIT) and "internal-infiltration" (AIMI) processed wires. Additionally, examination of the pinning mechanism showed that when scaled to the peak in the pinning curve, the films follow the grain boundary, or surface, pinning mechanism quite well, and are similar to the response seen for C doped PIT and AIMI strands, in contrast to the behavior seen in undoped PIT wires, in which deviations are seen at high b (b = B/Bc2 ). On the other hand, the magnitude of the pinning force was similar for the thin films and AIMI conductors, unlike the values from connectivity-suppressed PIT strands.
RESUMO
Significantly enhanced critical current density (Jc) for MgB2 superconducting wires can be obtained following the advanced internal Mg infiltration (AIMI) route. But unless suitable precautions are taken, the AIMI-processed MgB2 wires will exhibit incomplete MgB2 layer formation, i.e. reduced superconductor core size and hence suppressed current-carrying capability. Microstructural characterization of AIMI MgB2 wires before and after the heat treatment reveals that the reaction mechanism changes from a "Mg infiltration-reaction" at the beginning of the heat treatment to a "Mg diffusion-reaction" once a dense MgB2 layer is formed. A drastic drop in the Mg transport rate from infiltration to diffusion causes the termination of the MgB2 core growth. To quantify this process, a two-stage kinetic model is built to describe the MgB2 layer formation and growth. The derived kinetic model and the associated experimental observations indicate that fully reacted AIMI-processed MgB2 wires can be achieved following the optimization of B particle size, B powder packing density, MgB2 reaction activation energy and its response to the additions of dopants.