摘要
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.
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Evidence suggests that explicit reappraisal has limited regulatory effects on high-intensity emotions, mainly due to the depletion of cognitive resources occupied by the high-intensity emotional stimulus itself. The implicit form of reappraisal has proved to be resource-saving and therefore might be an ideal strategy to achieve the desired regulatory effect in high-intensity situations. In this study, we explored the regulatory effect of explicit and implicit reappraisal when participants encountered low- and high-intensity negative images. The subjective emotional rating indicated that both explicit and implicit reappraisal down-regulated negative experiences, irrespective of intensity. However, the amplitude of the parietal late positive potential (LPP; a neural index of experienced emotional intensity) showed that only implicit reappraisal had significant regulatory effects in the high-intensity context, though both explicit and implicit reappraisal successfully reduced the emotional neural responses elicited by low-intensity negative images. Meanwhile, implicit reappraisal led to a smaller frontal LPP amplitude (an index of cognitive cost) compared to explicit reappraisal, indicating that the implementation of implicit reappraisal consumes limited cognitive control resources. Furthermore, we found a prolonged effect of implicit emotion regulation introduced by training procedures. Taken together, these findings not only reveal that implicit reappraisal is suitable to relieve high-intensity negative experiences as well as neural responses, but also highlight the potential benefit of trained implicit regulation in clinical populations whose frontal control resources are limited.
Subject(s)
Humans , Emotional Regulation , Electroencephalography , Evoked Potentials/physiology , Cognition/physiology , Emotions/physiology摘要
The COVID-19 pandemic has become a serious global public health threat with more than 540 million infections and 6.32 million cases of death as of 25 June, 2022. Understanding whether COVID-19 patients can obtain persistent immune protection after recovery is crucial for vaccine development, disease control and epidemic forecast. The persistent immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly derived from the immune memory. Thus, the generation and maintenance of immune memory specifically targeted to the virus were reviewed in this paper.
摘要
Objective To improve the understanding of clinician' treatment of pregnancy with acute lymphoblastic leukemia. Method To analyze tretrospectively the diagnosis and treatment process of 1 case with acute lymphoblastic leukemia from December 13, 2016, and discuss the selection of the timing of termination of pregnancy. Results The patient was a 28 years old female. She was dignosed for acute lymphocytic leukemia in the third trimester. She bore a healthy baby boy in caesarean section after a dexamethasone treatment for two days. Then she recevied a series of standard chemotherapy. But she suffered a cerebral hemorrhage during treatment, and surgical pathology made a definite dignosis of central nervous system leukemia.Finally, She was out of danger after rescue. Conclusion Postoperative chemotherapy is a feasible option for the treatment of acute leukemia after the termination of pregnancy.
摘要
Castration-resistant prostate cancer [CRPC] progression after androgen deprivation therapy shows upregulated expression of androgen receptor [AR] splice variants, induced epithelial-to-mesenchymal transition phenotypes and enhanced stem cell characteristics, all of which are associated with resistance to enzalutamide. Since there is no curative treatment for CRPC, innovative treatments are urgently needed. In our recent study, we found that resistance to enzalutamide was partly due to deregulated expression of microRNAs such as miR-34a, miR-124, miR-27b, miR-320 and let-7, which play important roles in regulating AR and stem cell marker gene expression that appears to be linked with resistance to enzalutamide. Importantly, we found that Bio-Response 3,3' -diindolylmethane [BR-DIM] treatment in vitro and in vivo caused downregulation in the expression of wildtype AR. The AR splice variants, Lin28B and EZH2, appear to be deregulated through the re-expression of let-7, miR-27b, miR-320 and miR-34a in human prostate cancer [PCa]. BRDIM administered in clinical trials was well tolerated, and 93% of patients had detectable prostatic DIM levels. The inhibitory effects of BR-DIM on AR and AR target gene such as prostate-specific antigen were also observed in the clinical trial. Our preclinical and clinical studies provide the scientific basis for a 'proof-of-concept' clinical trial in CRPC patients treated with enzalutamide in combination with BRDIM. This strategy could be expanded in future clinical trials in patients with PCa to determine whether or not they could achieve a better treatment outcome which could be partly mediated by delaying or preventing the development of CRPC
摘要
AIM:To investigate the role of anti-miR-21 oligonucleotide ( AMO) in the anti-leukemic activity of decitabine (DCA) in vitro.METHODS:AMO and scramble oligonucleotide (SCR) were constructed and transfected into HL-60 cells.The miR-21 expression was analyzed by real-time PCR to identify the transfection efficiency .The cells were treated with DCA at gradient concentrations (0.5, 2.0 and 4.0 μmol/L) for 48 h.The mRNA expression of human period circadian protein 3 (hPer3) was detected by real-time PCR.The early apoptotic rates were determined by flow cy-tometry with Annexin V/PI staining.Mean fluorescence intensities ( MFI) of CD117 and CD11b were also measured by flow cytometry.RESULTS:The miR-21 relative expression level in AMO group was significantly lower than that in blank group and SCR group (P<0.01).IC50 of DCA in AMO group was significantly lower than that in blank group and SCR group (P<0.01).With the same concentration of DCA, the early apoptotic rate, the mRNA expression of hPer3 and the MFI of CD11b in AMO group were significantly higher than those in blank group and SCR group (P<0.01).The MFI of CD117 in AMO group were significantly lower than those in blank group and SCR group ( P<0.01 ) .CONCLUSION:Activation of hPer3 expression plays an important role in enhanced anti-leukemic activity of decitabine by AMO in vitro.
摘要
The Raf kinase inhibitory protein (RKIP) has been demonstrated to modulate different intracellular signaling pathways in cancers. Studies have shown that RKIP is frequently downregulated in cancers; therefore, attempts have been made to upregulate the expression of RKIP using natural and synthetic agents for the treatment of human malignancies. Moreover, various regulators such as specific proteins and microRNAs (miRNAs) that are involved in the regulation of RKIP expression have also been identified. RKIP mechanistically modulates the apoptotic regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling. Because of its critical role in human cancers, RKIP has drawn much research attention, and our understanding is expanding rapidly. Here, we summarize some of the biological complexities of RKIP regulation. However, we restrict our discussion to selected tumors by focusing on TRAIL, miRNAs and natural agents. Emerging evidence suggests a role for natural agents in RKIP regulation in cancer cells; therefore, naturally occurring agents may serve as cancer-targeting agents for cancer treatment. Although the literature suggests some advancement in our knowledge of RKIP biology, it is incomplete with regard to its preclinical and clinical efficacy; thus, further research is warranted. Furthermore, the mechanism by which chemotherapeutic drugs and novel compounds modulate RKIP and how nanotechnologically delivered RKIP can be therapeutically exploited remain to be determined.
Subject(s)
Humans , Male , Apoptosis , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasms/genetics , Phosphatidylethanolamine Binding Protein/genetics , Protein Interaction Maps , Signal Transduction , TNF-Related Apoptosis-Inducing Ligand/genetics摘要
<p><b>OBJECTIVE</b>To investigate the health status of the thyroid and related influencing factors in the seamen in Zhoushan, China.</p><p><b>METHODS</b>A total of 136 coastal seamen (coastal group), 104 deep-sea seamen (deep-sea group), and 272 base staff (base group) who underwent physical examinations in 2014 were selected. Questionnaire survey and ultrasound were performed, and levels of thyroid hormone and urinary iodine were measured.</p><p><b>RESULTS</b>Compared with the coastal group and the base group, the deep-sea group had a significantly higher rate of abnormal ultrasound findings (49.04% vs 30.88%/28.67%, P<0.05), as well as a significantly higher rate of abnormal serum free thyroxine (FT4) (25.00% vs 9.56%/6.25%, P<0.05). The logistic regression analysis showed that in the coastal group, the risk factors for thyroid abnormality on ultrasound were obesity shown by body mass index (BMI) (OR=2.55, 95% CI=1.13~4.13) and annual working time>6 months (OR=4.25, 95% CI=2.02~8.26) (both P<0.05); in the deep-sea group, the risk factors for thyroid abnormality on ultrasound were obesity shown by BMI (OR=3.45, 95% CI=1.28~7.02) and annual working time>6 months (OR=5.33, 95% CI=3.18~9.23) (both P<0.05).</p><p><b>CONCLUSION</b>The thyroid abnormality in deep-sea seamen is caused by various reasons and is correlated with annual working time, working environment and area, and iodine nutritional status.</p>
Subject(s)
Humans , Male , Body Mass Index , China , Health Status , Iodine , Urine , Naval Medicine , Occupations , Risk Factors , Surveys and Questionnaires , Thyroid Function Tests , Thyroid Gland , Diagnostic Imaging , Pathology , Thyroxine , Blood , Ultrasonography摘要
Objective To construct luciferase reporter vector containing full-length high-mobility group box 1 ( HMGB1, GenBank NM-010439) promoter for the screening of medicine. Methods The full-length HMGB1 promoter was amplified by polymerase chain reaction ( PCR) , and then was inserted into GV238 vector to construct plasmid GV238-HMGB1-P-Luc. GV238-HMGB1-P-Luc combined with internal reference plasmid pRL was co-transfected into Hela cells ( GV238-HMGB1-P-Luc group, which served as positive control group) . Plasmid pGL3-basic combined with pRL was co-transfected into Hela cells (pGL3-basic group, which served as negative control group) . Additionally, lipopolysaccharides ( LPS, 0.2 μg/mL) was used as the activator for the positive control group (LPS group), and then sodium butyrate (SB, 10 mmol/L) was used as the inhibitor for LPS group ( SB group) . At the end of experiment hour 24, luciferase activity was detected. Results The results of digestion, amplification, sequencing and identification showed that the full length of HMGB1 promoter was 2 140 bp, and the DNA sequence was correct, without mutation. Luciferase activity in GV238-HMGB1-P-Luc group was increased as compared with that of the pGL3-basic group ( P<0.05) . Luciferase activity in the LPS group was increased ( P<0.01, compared with that of GV238-HMGB1-P-Luc group) , and then was decreased after the administration of SB ( P<0.01, compared with that of the LPS group) . Conclusion A model of luciferase reporter vector containing HMGB1 promoter has been successfully constructed. Its activity can be increased by LPS, and then is in hibited by SB. The model can be used for further screening of medicine with the activities of regulating HMGB1 promoter.
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Objective To explore the validity and reliability of Nursing Professional Values Scale in registered nurses.Methods Demographic questionnaires and the Revised Nursing Professional Values Scale were used among 280 registered nurses.Results The Cronbach's α was 0.94.The factor analysis extracted 4 factors which could account for 59.55% variances.These four factors were defined as professional characteristic,providing care,behaviorist,and trust.The Cronbach's α for these four factors were 0.89,0.87,0.86 and 0.70 respectively.Conclusions The Revised Nursing Professional Values Scale possesses desirable validity and reliability in registered nurses,and is a psychometric good instrument of professional value.
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To investigate the effects of active ingredients of Plastrum Testudinis (PT) on serum deprivation-induced apoptosis of epidermal stem cells (ESCs).
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To observe the effects of Niupo Zhibao Pellet, a compound traditional Chinese herbal medicine, on high-mobility group box-1 protein (HMGB1) expression in lung tissues of rats with endotoxin shock.
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BACKGROUND: Stem cell differentiation potential is strongly correlated with culture condition. The alteration in scaffold material surface function, three dimensional (3D) structure, and addition of growth factors can control stem cell proliferation and differentiation.OBJECTIVE: To develop 3D macroporous scaffolds with optimal porosity and porous structure to provide a microenvironment that promotes the growth of multi-potent stem cells.DESIGN: Repetitive measurement.SETTING: Department of Anatomy, College of Basic Medicine, Guangzhou University of Chinese Medicine.MATERIALS: Healthy adult SD rats were provided by the Experimental Animal Center in Guangzhou University of Chinese Medicine. Chitosan and basic fibroblast growth factor (bFGF) were purchased from Sigma Corporation (St. Louis,MO).METHODS: The experiment was performed at the Department of Anatomy, College of Basic Medicine, Guangzhou University of Chinese Medicine from March 2003 to December 2006. Using a freeze-drying method, 3D macroporous scaffolds made of different ratios of chitosan-gelatin with bFGF were fabricated that could release bFGF with controlled porosity and porous structure. Bone marrow was obtained from the femur and tibia of SD rats, and mesenchymal stem cells (MSCs) were isolated, cultured and seeded on the scaffolds with bFGF. MSCs seeded on scaffolds with no bFGF served as control. The procedure during experiment was accorded with animal ethical requirements.MAIN OUTCOME MEASURES: 3D structure and release performance of the scaffolds were observed by ELISA and scanning electron microscope; the effect of 3D macroporous scaffolds that released bFGF on MSC growth and viability were observed by HE staining, MTT, cell counting and SEM.RESULTS: There was no significant difference in pore size between scaffolds with and without bFGF (P > 0.05). Scaffolds with bFGF significantly improved MSC survival rate, promoted cell adhesion, proliferation, and viability compared with scaffolds without bFGF (P < 0.05).CONCLUSION: The results suggest that 3D macroporous scaffolds with bFGF release improve MSC survival on scaffolds,and lay a foundation for its application in tissue engineering.
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Objective To explore the effects of impaired glucose metabolism and impaired blood lipoprotein metabolism on heart rate variability(HRV) in aged male hypertension patients and to have an insight into the correlation between the years of impaired glucose metabolism and the patients’ HRV. Methods 120 male subjects were divided into three groups: simple hypertension patients (group A, 40 people), hypertension patients with diabetes mellitus (group B, 40 people), and hypertension patients with diabetes mellitus and impaired blood lipoprotein metabolism (group C, 40 people). All subjects had 24h recordings of ECG. The data of HRV time domain were collected and analyzed to gain an insight into the effects of the impaired glucose metabolism and impaired blood lipoprotein metabolism on patients’ HRV. In group C, patients were divided into normal TC subgroup and high TC subgroup according to the index of TC (TC
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Objective To observe the diagnostic value of telomerase,VEGF,CD44_ V6 ,MMP_2,MMP_9and their combined examination in distinguishing malignant pleural effusion from benign one.Methods Sixty patients with pleural effusions were observed,thirty of them sufferring from malignant pleural effusion and thirty of them sufferring from benign one.The expression of telomerase,CD44_ V6 ,VEGF,MMP_2,MMP_9were tested in the pleural effusion by RT-PCR and ELISA technique.The sensitivity and the specificity of each examination method were calculated,in order to find out appropriate combination.Results As single-item detection,the diagnosetic value of VEGF was the best,the cutoff of VEGF was 181.1pg/ml,the sensitivity of VEGF examination was 90.0%,and the specificity was 86.7%.The sensitivity and the specificity of combined examination VEGF+CD44_ V6 and VEGF+MMP_2 were the best,the sensitivity of VEGF+CD44_ V6 was 83.3%,and the specificity was 90.0%.The sensitivity of VEGF+MMP_2 was 80.0% and the specificity was 93.3%.Conclusion The level of telomerase,VEGF,CD44_ V6 ,MMP_2,MMP_9in malignant pleural effusion is clearly higher than that in benign pleural one,the difference having significant statistic meaning.VEGF has higher sensitivity and specificity .Of combined examination,VEGF+CD44_ V6 and VEGF+MMP_2 have higher sensitivity and specificity.
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To investigate the osteogenesis characteristics of cultured rat mesenchymal stem cells (MSCs) under bone induction condition.
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<p><b>OBJECTIVE</b>To observe the influence of Niupo Zhibao pellet (NZP) on transforming growth factor-beta1 (TGF-beta1) and its receptor's expression.</p><p><b>METHODS</b>Endotoxic shock model was established by intravenous injection of lipopolysaccharide (LPS) 1.5 mg/kg and intraperitoneal injection of D-galactosamine 100 mg/kg, and intervened by NZP, TGF-beta1 and its receptor's expression in lung tissue were detected by immunohistochemical method.</p><p><b>RESULTS</b>NZP could enhance the TGF-beta1 and its receptor's expression in endotoxic shock lung tissue, and reduce the injury of lung.</p><p><b>CONCLUSION</b>The mechanism of NZP in reducing endotoxic shock lung injury is possibly related with its effect in enhancing the TGF-beta1 and its receptor's expression in lung tissue.</p>
Subject(s)
Animals , Female , Male , Rats , Drugs, Chinese Herbal , Pharmacology , Galactosamine , Lipopolysaccharides , Rats, Sprague-Dawley , Receptors, Transforming Growth Factor beta , Respiratory Distress Syndrome , Metabolism , Shock, Septic , Metabolism , Transforming Growth Factor beta , Transforming Growth Factor beta1摘要
OBJECTIVE: To observe the effect of electro-acupuncture of Neiguan (PC 6) on mean systemic arterial blood pressure and plasmic concentrations of NO and TNFalpha in endotoxin shock rats. METHODS: The model of endotoxin shock was induced by lipopolysaccharide (1.5 mg/kg i.v.) and D-galactosamine (100 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) and electro-acupuncture of bilateral Neiguan (PC 6) were administered. A catheter was inserted into the right subclavian artery to record the change of blood pressure and the blood was abstracted out and centrifuged to determine the NO and TNFalpha concentrations. RESULTS: Electro-acupuncture of Neiguan (PC 6) retrieved the blood pressure and reduced the plasmic NO and TNFalpha concentrations. CONCLUSION: Electro-acupuncture of Neiguan (PC 6) expresses an anti-endotoxin shock effect by repressing the plasmic NO and TNFalpha concentrations smoothly and retrieving the blood pressure stably.
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<p><b>OBJECTIVE</b>To study the molecular mechanism of microcystin (MC) induced liver tumorigenesis in rats.</p><p><b>METHODS</b>The two-stage-medium-term tumorigenesis theory was applied to establish the animal model, and the effect of MC in liver tumor formation was evaluated by the Albert gamma-GT methods, and then, the immunohistochemical technique and image analysis were used to study the expression of the bcl-2 and bax genes during tumorigenesis.</p><p><b>RESULTS</b>(1) MC enhanced the formation of gamma-GT foci in liver (100%), which was significantly higher than the diethylnitrosamine (DEN) control group (22.22%) (P < 0.05). (2) MC decreased the expression of bax gene. The intensity and area of bax gene expression in the pure MC toxin group were 0.028 3 AODV and 0.007 3 ( micro m(2)/ micro m(2)) and in the DEN control group were 0.065 5 AODV and 0.024 4 ( micro m(2)/ micro m(2)), respectively. The intensity and areas of bax gene expression in the pure MC toxin group were significantly lower than those in the DEN control group (P < 0.05). (3) MC increased the expression of bcl-2 gene. The intensity and area of bcl-2 gene expression in the pure MC toxin group wee 0.097 7 AODV and 0.031 5 ( micro m(2)/ micro m(2)), respectively, and in the DEN control group were 0.046 0 AODV and 0.020 5 ( micro m(2)/ micro m(2)) respectively (P < 0.05).</p><p><b>CONCLUSION</b>(1) MC can strongly promote liver tumorigenesis. (2) The changes of bcl-2 and bax gene expression possibly play an important role in the MC induced liver tumor formation.</p>
Subject(s)
Animals , Mice , Rats , Carcinogens , Toxicity , Immunohistochemistry , Liver , Metabolism , Pathology , Liver Neoplasms , Metabolism , Pathology , Microcystins , Peptides, Cyclic , Toxicity , Proto-Oncogene Proteins , Proto-Oncogene Proteins c-bcl-2 , Rats, Wistar , bcl-2-Associated X Protein摘要
<p><b>OBJECTIVE</b>To make a thorough study on the clinicopathologic significance of the three-dimensional structural alteration of the p53 protein in papillary thyroid carcinomas and to provide an objective criterion for the evaluation of PTC prognosis.</p><p><b>METHODS</b>A total of 41 PTC cases were enrolled. Techniques including polymerase chain reaction with single strand conformational polymorphism (PCR-SSCP), DNA sequencing, computerized three-dimensional protein modeling by means of international shared resources and related software analysis were used.</p><p><b>RESULTS</b>15 cases with p53 gene mutation defined as Group I were detected in totally 41 PTC cases. No p53 gene mutation was found in the rest 26 cases which were classified as Group II. The differences in lymph node metastatic rate, distant metastatic rate, age, sex, size of the lesion between Group I and Group II were not significant (P > 0.05). The alterations of the amino acid residues of 9 PTC cases out of the 15 p53-gene mutated patients (Group I) were either located in the p53-protein domains, mainly the core domain and the non-specific DNA binding basic domain, or the severely defect cases with the formation of widely divergent structures. It was found that the alterations of the structure of the core domain could directly check the binding of p53 protein to its target DNA molecules. In addition, the alterations of the structure of the basic domain could indirectly prohibit the binding. The ones mentioned above were classified as Group Ib. The rest of six cases with their p53 protein amino acid residues mutated beyond the domains were grouped as Group Ia. The differences in lymph node metastatic rate, distant metastatic rate between Group Ib and Group Ia were statistically significant (P < 0.01, P < 0.05) respectively.</p><p><b>CONCLUSIONS</b>The alterations of the three-dimensional structure of p53-protein is considered as one of the morphological basis of the progression and heterogeneity of PTC. They render an authentic evidence for the selection of the clinical cases with a poor risk for metastasis.</p>