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Objective: To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH). Methods: A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People's Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher's exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M(Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson's correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios (OR) and 95% confidence intervals (CI) were calculated. P<0.05 was considered significant. Results: There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 µmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) µmol/L] between the CCH and control groups (P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson's correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH (r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH (OR=1.169,95%CI 1.063-1.286,P=0.001). Conclusions: The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.
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Isquemia Encefálica , Hiperlipidemias , Hipertensão , MicroRNAs , Humanos , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Ácido Úrico , MicroRNAs/genética , HomocisteínaRESUMO
Objective: To analyze clinicopathological characteristics of patients with uterine papillary serous carcinoma (UPSC) in China, and investigate roles of TXNDC17 protein in UPSC clinicopathological characteristics and prognosis. Methods: Fifty-five patients with UPSC treated in Women's Hospital School of Medicine Zhejiang University from 2003 to 2016 were analysed retrospectively. Immunohistochemistry (IHC) were performed to TXNDC17 and BECN1 (Beclin 1 protein, a key regulator of autophagy) protein expression respectively. Kaplan-Meier was used to calculate the cumulative survival rate, Log-rank test was performed to compare the difference in cumulative survival rate among patients with different clinicopathological characteristics, and Cox regression model was used to analyze the related between TXNDC17 expression and prognosis of UPSC patients. Results: The median age of the 55 UPSC patients was 63(49, 79) years, 43.6%(24/55) with late stages (stage â ¢/â £), and 32.7 % (18/55) exhibiting more than half of myometrium invasion were enrolled. Notably, 28 (50.9%) patients had TXNDC17 protein overexpression, and associated with BECN1 overexpression(P=0.023). Besides, co-expression of TXNDC17 and BECN1 occurred at an advanced stage and deep myometrial invasion (P=0.013,0.009). The cumulative survival rate of TXNDC17 overexpression(37.4% vs 91.5%),FIGO â ¢/â £ stage(44.1% vs 70.1%), deep myometrium invasion(36.1% vs 75.4%) and BECN1 overexpression(0 vs 83.0%)patients was low (P<0.05). The multivariate proportional hazards model revealed that myometrial invasion and TXNDC17 overexpression were associated with prognosis of UPSC patients. Conclusions: This study shows that TXNDC17 overexpression is associate with poor survival in UPSC patients. Co-expression of TXNDC17 and BECN1 shows characteristics of advanced stages and deep myometrial invasion. TXNDC17 may be a potential predictor or target in UPSC therapeutics..
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Carcinoma , Cistadenocarcinoma Seroso , Neoplasias Uterinas , Carcinoma/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To investigate the effect of triptolide, a specific inhibitor of heat shock protein 70 (HSP70), on apatinib resistance in gastric cancer cells line MKN45. Methods: The apatinib-resistant cells (MKN45/AR) and MKN45 parental cells were treated with apatinib, triptolide and apatinib combined with triptolide, respectively. CCK-8 assay was performed to determine the half maximal inhibitory concentration (IC(50)) of MKN45/AR and MKN45 cells in the presence of different treatment. The mRNA expression of heat shock protein gene (HSPA1A and HSPA1B) was detected by RT-PCR, while the protein expression of heat shock protein 70 was analyzed using Western blot in MKN45/AR and MKN45 cells. Results: The IC(50) values of apatinib-sensitive and apatinib-resistant MKN45 cells were 10.411 µmol/L and 70.527 µmol/L, respectively, showing a significant difference (P<0.05). The mRNA expression of HSPA1A and HSPA1B in MKN45/AR cells was significantly higher than that in MKN45 cells (P<0.001). The protein expression of heat shock protein 70 was significantly decreased after 0.25 µmol/L triptolide treatment in MKN45/AR cells (P<0.01). When heat shock protein 70 was inhibited by triptolide, the IC(50) value of apatinib in MKN45/AR cells was reduced to 11.679 µmol/L, which was significantly lower than cells treated with apatinib alone (P<0.05). Conclusions: The apatinib-resistant MKN45 cells have high levels of heat shock protein 70. Low doses of triptolide can significantly inhibit heat shock protein 70, leading to reverse the resistance phenotype of MKN45/AR cells. Therefore, inhibition of heat shock protein 70 provides a new therapy strategy for patients with apatinib resistance.
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Antineoplásicos/farmacologia , Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Fenantrenos/farmacologia , Piridinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Compostos de Epóxi/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Dose Máxima Tolerável , Neoplasias Gástricas/patologiaRESUMO
Objective: To evaluate etoposide, methotrexate and dactinomycin (EMA) /cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN) . Methods: A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver, brain, or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital, School of Medicine, Zhejiang University from January 2001 to December 2015. All of the patients were treated by EMA/CO regimen and followed up to death or December 2017. The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated. Results: All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18, median 13.0) . Twenty patients (83%, 20/24) received EMA/CO regimen as primary treatment and 4 patients (17%, 4/24) had a history of failed chemotherapy. Seven patients (29%, 7/24) had metastasis of liver or brain and 17 patients (71%, 20/24) had no metastasis of liver and brain. Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses) . Sixteen patients achieved complete remission and 8 patients showed drug-resistant. The complete remission rate was 67% (16/24) and the resistance rate was 33% (8/24) . Of the 16 patients who got complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases were treated by chemotherapy combined with surgery. For the 8 patients who showed drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission, 1 case received methotrexate, dactinomycin and cyclophosphamide (MAC) regimen and got remission, 2 cases gave up treatment because of economic factors. The side effects of EMA/CO mainly included â ¢-â £ degree neutropenia, anemia and alopecia. The incidence of â ¢-â £ degree neutropenia during the treatment of EMA/CO was 21.6% (36/167) , the incidence of anemia was 96.4% (161/167) , and the incidence of alopecia was 60.5% (101/167) . In these 24 ultra high-risk GTN patients, 4 patients died during follow-up. In the 20 patients who got complete remission, no recurrence or secondary tumor by chemotherapy were occurred. Conclusion: EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dactinomicina/administração & dosagem , Dactinomicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/patologia , Humanos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Estadiamento de Neoplasias , Gravidez , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
The article "Effect of atorvastatin on pulmonary arterial hypertension in rats through PI3K/AKT signaling pathway", by Y.-Y. Wang, X.-D. Cheng, H. Jiang, published in Eur Rev Med Pharmacol Sci 2019; 23 (23): 10549-10556-DOI: 10.26355/eurrev_201912_19696-PMID: 31841211 has been retracted by the Authors. After publication, issues were raised on PubPeer about the reliability of the published results, in particular, of Figures 2 and 3. The authors stated that the article presents some inaccuracies as the data cannot be repeated by further research. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19696.
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In the surgical treatment of adenocarcinoma of the esophagogastric junction (AEG), the scope of lymph node dissection, surgical approach selection, extent of tumor resection and digestive tract reconstruction have always been controversial, with the digestive tract reconstruction in AEG facing many challenges especially. The digestive tract reconstruction is related to the extent of resection. At present, the digestive tract reconstruction after total gastrectomy includes Roux-en-Y anastomosis, jejunum interposition and its derivatives. According to different reconstruction methods, they can be divided into tube anastomosis, linear anastomosis and manual anastomosis. Anti-reflux digestive tract reconstruction after proximal gastrectomy mainly includes esophagogastric anastomosis, interposition jejunum and double channel anastomosis. At present, double channel anastomosis is the most common reconstruction method in China. Based on the concept of interposition tubular stomach and reconstruction of gastric angle for anti-reflux, we propose "Giraffe" anastomosis, which moves artificial fundus and His angle downward to retain more residual stomach, showing good gastric emptying and anti-reflux effect. In this paper, combined with our clinical experience and understanding, we discuss the selection and technical key points of digestive tract reconstruction methods in AEG, and suggest that composite anti-reflux mechanism design may be the development trend of anti-reflux reconstruction in the future. The composite mechanism includes the retention of gastric electrical pacemaker in greater curvature of the middle part of gastric body to increase the emptying capacity of residual stomach, the reconstruction of gastric fundus and His angle anti-reflux barrier, and the establishment of an interposition tubular stomach acting as a buffer zone in Giraffe construction, and so on.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Anastomose em-Y de Roux , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Gastrectomia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.
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Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Gastrectomia , Procedimentos de Cirurgia Plástica , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso , Neoplasias Esofágicas/cirurgia , Esofagite Péptica/etiologia , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Refluxo Gastroesofágico/etiologia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: The aim of this study was to explore the effect of neurotrophin-3 (NT-3) on the repair of spinal cord injury (SCI) through the mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: The rat model of SCI was first successfully established using the impactor (SCI group). Meanwhile, control group and NT-3 treatment group were set up as well. Basso-Beattie-Bresnahan (BBB) score was given and blood, and spinal cord tissues were collected from rats. Subsequently, serum indexes were detected, including glucose (Glu), creatinine (Cr), K+, Na+, the content of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-ß (TNF-ß), and the level of myeloperoxidase (MPO). Moreover, the morphological changes were observed via hematoxylin-eosin (HE) staining. The gene and protein expressions of glial fibrillary acidic protein (GFAP) and MAPK were determined through Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting, respectively. Furthermore, the effect of the MAPK signaling pathway on SCI was comprehensively observed. RESULTS: In SCI group, the rats could not crawl autonomously with the loss of motor function and paraplegia. Meanwhile, the levels of Glu, Cr, Na+, IL-6, IL-1ß, TNF-ß, and MPO were all significantly up-regulated. According to the results of HE staining, spinal nerve fibers disappeared with significant syringomyelia in SCI group. Meanwhile, the aggregation of nerve fibers was observed without apparent tissue bleeding, edema, and cell deformation in NT-3 group. QRT-PCR results demonstrated that SCI group showed remarkably higher levels of GFAP, MAPK, and c-Jun N-terminal kinase (JNK) (p<0.05), while it showed a markedly lower level of ERK2 than NT-3 group (p<0.05). In NT-3 group, the protein expression of MAPK in myocardial tissues was remarkably lower than that of SCI group (p<0.05). CONCLUSIONS: NT-3 can inhibit the MAPK signaling pathway, thereby promoting the repair of SCI.
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Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neurotrofina 3/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases , RatosRESUMO
Objective: To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG). Methods: Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux. Result: All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9. Conclusion: Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.
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Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia , Gastrectomia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Gástricas/cirurgia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of atorvastatin on pulmonary arterial hypertension (PAH) in rats and to observe its specific regulatory mechanism through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. MATERIALS AND METHODS: The model of PAH was successfully established in rats via hypoxia feeding. All rats were divided into three groups, including Control group (n=15), PAH model group (Model group, n=15) and atorvastatin treatment group (Ator group, n=15). Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) were detected via enzyme-linked immunosorbent assay (ELISA). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined as well. Meanwhile, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining. Furthermore, the apoptosis level of lung tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In addition, the expression levels of PI3K/AKT signaling pathway and apoptotic genes in lung tissues were detected via quantitative Polymerase Chain Reaction (qPCR). RESULTS: In Model group, the levels of TNF-α and IL-6 increased significantly, while the level of NO decreased. Both RVSP and RVHI in Model group were significantly higher than those of Control group and Ator group (p<0.05). The results of HE staining revealed that Model group showed significantly severe lung tissue injury (p<0.05). According to the results of TUNEL staining, the number of apoptotic cells in lung tissues in Model group was significantly smaller than that of Ator group (p<0.05). Meanwhile, the expression level of cysteinyl aspartate-specific proteinase-3 (Caspase-3) in Model group was markedly lower than that of Ator group (p<0.05). However, the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was markedly higher than that of Ator group (p<0.05). In Ator group, the expression levels of PI3K and AKT in lung tissues were remarkably higher than those of Model group (p<0.05). All the above results indicated that atorvastatin could effectively up-regulate the expressions of PI3K and AKT (p<0.05). CONCLUSIONS: Atorvastatin regulates the symptoms of PAH in rats through activating the PI3K/AKT signaling pathway.
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Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Atorvastatina/uso terapêutico , Modelos Animais de Doenças , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , Ratos , Regulação para Cima/efeitos dos fármacosRESUMO
Neutron diffraction data from a crystal of carbonmonoxymyoglobin were refined by PROLSQ, a modern restrained least-squares procedure in reciprocal space, in conjunction with a solvent analysis technique, to a final R-factor of 11.3%. The ligand CO occupies two sites and its binding conformations are distorted from the linear conformation. The N epsilon atom of the distal histidine residue is deprotonated (not deuterated), and a water molecule is bound to the N delta atom of the distal histidine. The side-chain of Lys56 (D6) exists in two alternative charge-binding sites. His24 (B5) and His119 (GH1) share a hydrogen atom. His12 (A10) and His36 (C1) are deprotonated. The deprotonated imidazole ring of His12 (A10) may act as a hydrogen-bond acceptor. The heme group is planar within 0.09 A root-mean-square (r.m.s.) deviation from planarity. The solvent environments for the two propionic acid groups are different. The side-chain of Arg45 (CD3) forms hydrogen bonds with the side-chain of Asp60 (E3) and one of the two propionic acid groups. An average N-2H . . . O angle in helical regions is 147 (+/- 11) degrees. Eleven main-chain amide hydrogen atoms from hydrophobic residues do not exchange with deuterium. The overall atomic occupancy factors for the main-chain and side-chain atoms are quite uniform, at 0.97 (+/- 0.07) and 0.93 (+/- 0.10), respectively, as shown by an occupancy analysis made at the end of the refinement procedure.
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Mioglobina/química , Sequência de Aminoácidos , Sítios de Ligação , Monóxido de Carbono/metabolismo , Cristalização , Análise de Fourier , Heme/metabolismo , Matemática , Modelos Moleculares , Dados de Sequência Molecular , Mioglobina/metabolismo , Nêutrons , Conformação Proteica , Espalhamento de RadiaçãoRESUMO
We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection.
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Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Hepatite B Crônica/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The present study was to investigate the dynamic changes of the induction of interleukin-2 (IL-2) production of spleen lymphocytes from the rats after operative trauma stress and the regulatory effect of continued electroacupuncture (EA) stimulation of "Zusanli" (St. 36) and "Lanwei" (Extra 33) points on the induction of IL-3 production of spleen lymphocytes from the injured rats. The results showed that the induction of IL-2 production of the rat spleen lymphocytes was significantly decreased on day 1, 3, 5, 7 (P < 0.05), and the minimum level was on day 3 after operative trauma at both dilution 1:8 and dilution 1:16. The induction of IL-2 production was reserved to nearly normal on day 10. Continued stimulation by EA on "St. 36" and "Extra 33" points on day 3, 5, 7 increased the induction of IL-2 production in various degrees at the two dilutions (P < 0.01), or P < 0.05). The results mentioned above implied that the immune function could be depressed by trauma stress. Continued EA stimulation could improve the immunosuppression induced by trauma stress.
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Abdome/cirurgia , Eletroacupuntura , Interleucina-2/biossíntese , Linfócitos/imunologia , Baço/patologia , Estresse Fisiológico/imunologia , Pontos de Acupuntura , Animais , Células Cultivadas , Seguimentos , Tolerância Imunológica/imunologia , Masculino , Ratos , Ratos Wistar , Baço/imunologiaRESUMO
The present study was to observe the dynamic changes of tyrosine protein kinase (TPK) activity in subcellular fractions in the early stage of activation of T lymphocytes from normal and traumatized rats, and the regulatory effect of electroacupuncture (EA) stimulation on it. The results showed that the activities of TPK in membranous and cytosolic fractions of activated T lymphocytes were increased on second 5, and the peak was on scond 45 after ConA stimulation. Then it was decreased gradually. Comparing with the control group, the activities of TPK in membranous and cytosolic fractions of activated T lymphocytes from the traumatized rats were inhibited in various degrees especially in membrane. EA of "Zusanli"(ST-36) and "Lanwei"(Extra 33) points could enhance the activity of TPK in subcellular fractions of activated T lymphocytes from the traumatized rats. The results indicated that EA stimulation could prevent the inhibition of activation of TPK induced by trauma stress, and contribute to transmembrane signal transduction of T lymphocytes.
Assuntos
Eletroacupuntura , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Estresse Fisiológico/imunologia , Estresse Fisiológico/terapia , Linfócitos T/enzimologia , Ferimentos e Lesões/complicações , Animais , Membrana Celular/enzimologia , Citosol/enzimologia , Modelos Animais de Doenças , Ativação Linfocitária , Masculino , Ratos , Ratos Wistar , Estresse Fisiológico/etiologia , Linfócitos T/imunologia , Linfócitos T/ultraestruturaRESUMO
The covalent modification of E. coli arginyl-tRNA synthetase by the 2',3'-dialdehyde derivative of tRNA(Arg) (tRNA(oxArg)) resulted in the complete inactivation of the ATP-PPi exchange and aminoacylation activities of the enzyme. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the ArgRS-tRNA(oxArg) covalent complexes indicated that two bands simultaneously appeared on the gel parallel with inactivation corresponding to different higher molecular weights. This result was different from that of the other aminoacyl-tRNA synthetase labeling systems as previously reported. Upon the ribonuclease treatment of the modified ArgRS, less than 15% of both the initial ATP-PPi exchange and aminocylation activities were recovered. During the whole process of labeling and RNase treatment, the two activities of the enzyme were closely associated.
Assuntos
Arginina-tRNA Ligase/metabolismo , Escherichia coli/enzimologia , RNA Bacteriano , Marcadores de Afinidade , Sítios de Ligação , RNA de Transferência de Arginina , Bases de SchiffRESUMO
OBJECTIVE: To observe the therapeutical effect of Fuzhengfang (FZF). METHODS: Therapeutic effect of FZF herbs on mice with Lewis lung cancer was observed, and its regulation on function of red blood cell immune system of the mice was also studied. RESULTS: FZF herbs could inhibit the growth of tumor, and increase the weight of mice with Lewis lung cancer. The quality of life of the mice was improved after treatment with FZF herbs. FZF herbs could increase the activity of red blood cell C3b receptors, reduce the quantity of red blood cell immune complexes, elevate the immune adherent function of red blood cells to tumor cells, raise activity of red blood cell immune adherent enhancing factors in serum, and lower the activity of red blood cell immune adherent inhibitory factors. Chemotherapy could inhibit the growth of tumor, but decrease the weight of mice with Lewis lung cancer. The quality of life of the mice was decreased after chemotherapy. Chemotherapy could reduce the activity of red blood cell C3b receptors, increase the quantity of red blood cell immune complexes, depress the immune adherent function of red blood cells to tumor cells, lower the activity of red blood cell immune adherent enhancing factors in serum, and raise the activity of red blood cell immune adherent inhibitory factors in serum. There was a significant difference between FZF herbs and chemotherapy. CONCLUSION: FZF herbs have a positive therapeutic effect in mice with Lewis lung cancer, and its mechanism might be associated with improving function of red blood cell immune system of mice with Lewis lung cancer.
Assuntos
Carcinoma Pulmonar de Lewis/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Eritrócitos/imunologia , Receptores de Complemento 3b/metabolismo , Animais , Complexo Antígeno-Anticorpo/metabolismo , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Formação de RosetaRESUMO
A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10(3.0 ± 0.4) tissue culture infective dose (TCID)(50) /mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8-96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9-100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9-100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.