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In the process of orthodontic tooth movement, the secretion of cytokines by immune cells or cell-cell interaction affects the regulation of osteoclast and osteoblast differentiation. Increasingly, studies have focused on the role in the immune system in orthodontic bone remodeling. Based on the biological role of different immune cells or cytokines, this article briefly presents the research progress of immunomodulation in orthodontic tooth movement and future perspective, hopefully providing a deeper and more comprehensive understanding of the biological mechanism in orthodontic tooth movement.
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As an important part of traditional Chinese medicine， the efficacy and scientificity of acupuncture have attracted more and more attention. In recent years， rigorous randomized controlled clinical trials have confirmed the efficacy of acupuncture on certain dominant diseases， and basic researches have partially revealed the mechanism of acupuncture for treating diseases. By analyzing published literatures and referring to relevant studies from our research team， this paper reviews the mechanisms of acupuncture for treating neurological and other diseases via regulating the autophagy-lysosomal pathway （ALP）. We found that acupuncture improved related pathologies in different disease models by up-regulating or down-regulating ALP， and there is a certain correlation between the distribution of acupoints and the one-way/two-way regulation of ALP； however， the current studies have some defects in experimental design and methodology， and the molecular mechanisms of acupuncture on ALP regulation remain to be further elucidated.
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Objective: To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on pulmonary vascular endothelial cells (PMVECs) injury in septic mice and its mechanism. Methods: The experimental research method was adopted. The primary ADSCs were isolated and cultured from the discarded fresh adipose tissue of 3 patients (female, 10-25 years old), who were admitted to the First Affiliated Hospital of Air Force Medical University undergoing abdominal surgery, and the cell morphology was observed by inverted phase contrast microscope on the 5th day. The expressions of CD29, CD34, CD44, CD45, CD73, and CD90 of ADSCs in the third passage were detected by flow cytometry. The third to the fifth passage of ADSCs were collected, and their exosomes from the cell supernatant were obtained by differential ultracentrifugation, and the shape, particle size, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin of exosomes were detected, respectively, by transmission electron microscopy, nano-particle tracking analysis and Western blotting. Twenty-four adult male BALB/c mice were adopted and were divided into normal control group, caecal ligation perforation (CLP) alone group, and CLP+ADSC-exosome group with each group of 8 according to random number table (the same grouping method below) and were treated accordingly. At 24 h after operation, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) levels of mice serum were detected by enzyme-linked immunosorbent assay, and lung tissue morphology of mice was detected by hematoxylin-eosin and myeloperoxidase staining, and the expression of 8-hydroxy-deoxyguanosine (8-OHdG) of mouse lung cells was detected by immunofluorescence method. Primary PMVECs were obtained from 1-month-old C57 mice regardless gender by tissue block method. The expression of CD31 of PMVECs was detected by immunofluorescence and flow cytometry. The third passage of PMVECs was co-cultured with ADSCs derived exosomes for 12 h, and the phagocytosis of exosomes by PMVECs was detected by PKH26 kit. The third passage of PMVECs were adopted and were divided into blank control group, macrophage supernatant alone group, and macrophage supernatant+ADSC-exosome group, with 3 wells in each group, which were treated accordingly. After 24 h, the content of reactive oxygen species in cells was detected by flow cytometry, the expression of 8-OHdG in cells was detected by immunofluorescence, and Transwell assay was used to determine the permeability of cell monolayer. The number of samples in above were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results: The primary ADSCs were isolated and cultured to day 5, growing densely in a spindle shape with a typical swirl-like. The percentages of CD29, CD44, CD73 and CD90 positive cells of ADSCs in the third passage were all >90%, and the percentages of CD34 and CD45 positive cells were <5%. Exosomes derived from ADSCs of the third to fifth passages showed a typical double-cavity disc-like structure with an average particle size of 103 nm, and the protein expressions of CD9, CD63 and TSG101 of exosomes were positive, while the protein expression of β-actin of exosomes was negative. At 24 h after operation, compared with those in normal control group, both the levels of TNF-α and IL-1β of mice serum in CLP alone group were significantly increased (with t values of 28.76 and 29.69, respectively, P<0.01); compared with those in CLP alone group, both the content of TNF-α and IL-1β of mice serum in CLP+ADSC-exosome group was significantly decreased (with t values of 9.90 and 4.76, respectively, P<0.05 or P<0.01). At 24 h after surgery, the pulmonary tissue structure of mice in normal control group was clear and complete without inflammatory cell infiltration; compared with those in normal control group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP alone group were more obvious; compared with those in CLP alone group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP+ADSC-exosome group were significantly reduced. At 24 h after operation, endothelial cells in lung tissues of mice in 3 groups showed positive expression of CD31; compared with that in normal control group, the fluorescence intensity of 8-OHdG positive cells of the lung tissues of mice in CLP alone group was significantly increased, and compared with that in CLP alone group, the fluorescence intensity of 8-OHdG positive cells in the lung tissues of mice in CLP+ADSC-exosome group was significantly decreased. The PMVECs in the 3rd passage showed CD31 positive expression by immunofluorescence, and the result of flow cytometry showed that CD31 positive cells accounted for 99.5%. At 12 h after co-culture, ADSC-derived exosomes were successfully phagocytose by PMVECs and entered its cytoplasm. At 12 h after culture of the third passage of PMVECs, compared with that in blank control group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant alone group was significantly increased (t=15.73, P<0.01); compared with that in macrophage supernatant alone group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant+ADSC-exosome group was significantly decreased (t=4.72, P<0.01). At 12 h after culture of the third passage of PMVECs, and the 8-OHdG positive fluorescence intensity of PMVECs in macrophage supernatant alone group was significantly increased; and compared with that in blank control group, the 8-OHdG positive fluorescence intensity of PMVECs in macrophage+ADSC-exosome supernatant group was between blank control group and macrophage supernatant alone group. At 12 h after culture of the third passage PMVECs, compared with that in blank control group, the permeability of PMVECs monolayer in macrophage supernatant alone group was significantly increased (t=6.34, P<0.01); compared with that in macrophage supernatant alone group, the permeability of PMVECs monolayer cells in macrophage supernatant+ADSC-exosome group was significantly decreased (t=2.93, P<0.05). Conclusions: Exosomes derived from ADSCs can ameliorate oxidative damage in mouse lung tissue, decrease the level of reactive oxygen species, 8-OHdG expression, and permeability of PMVECs induced by macrophage supernatant.
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Animals , Female , Humans , Male , Mice , Endothelial Cells/metabolism , Exosomes/metabolism , Lung Injury/metabolism , Mesenchymal Stem Cells/metabolism , Sepsis/pathologyABSTRACT
Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.
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Aged , Female , Humans , Male , Middle Aged , Aspirin/therapeutic use , Cardiovascular Diseases/prevention & control , China , Drug Therapy, Combination , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Rivaroxaban/therapeutic use , Secondary PreventionABSTRACT
Nanofibers can mimic natural tissue structure by creating a more suitable environment for cells to grow, prompting a wide application of nanofiber materials. In this review, we include relevant studies and characterize the effect of nanofibers on mesenchymal stem cells, as well as factors that affect cell adhesion and osteogenic differentiation. We hypothesize that the process of bone regeneration in vitro is similar to bone formation and healing in vivo, and the closer nanofibers or nanofibrous scaffolds are to natural bone tissue, the better the bone regeneration process will be. In general, cells cultured on nanofibers have a similar gene expression pattern and osteogenic behavior as cells induced by osteogenic supplements in vitro. Genes involved in cell adhesion (focal adhesion kinase (FAK)), cytoskeletal organization, and osteogenic pathways (transforming growth factor-β (TGF-β)/bone morphogenic protein (BMP), mitogen-activated protein kinase (MAPK), and Wnt) are upregulated successively. Cell adhesion and osteogenesis may be influenced by several factors. Nanofibers possess certain physical properties including favorable hydrophilicity, porosity, and swelling properties that promote cell adhesion and growth. Moreover, nanofiber stiffness plays a vital role in cell fate, as cell recruitment for osteogenesis tends to be better on stiffer scaffolds, with associated signaling pathways of integrin and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ). Also, hierarchically aligned nanofibers, as well as their combination with functional additives (growth factors, HA particles, etc.), contribute to osteogenesis and bone regeneration. In summary, previous studies have indicated that upon sensing the stiffness of the nanofibrous environment as well as its other characteristics, stem cells change their shape and tension accordingly, regulating downstream pathways followed by adhesion to nanofibers to contribute to osteogenesis. However, additional experiments are needed to identify major signaling pathways in the bone regeneration process, and also to fully investigate its supportive role in fabricating or designing the optimum tissue-mimicking nanofibrous scaffolds.
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BACKGROUND@#Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.@*METHODS@#In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.@*RESULTS@#The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.@*CONCLUSION@#Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
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Adult , Humans , Adaptor Proteins, Signal Transducing , Arteriosclerosis Obliterans/genetics , Autophagy , GRB2 Adaptor Protein , Phosphoproteins/metabolism , Phosphorylation , Protein Binding , Signal TransductionABSTRACT
OBJECTIVE@#To investigate the molecular mechanism of trichloroethylene (TCE) cardiac developmental toxicity on zebrafish embryos and to try to provide experimental data for related intervention.@*METHODS@#Zebrafish embryos were purchased from the National Zebrafish Resource Center. The embryos were divided into DMSO(control group), DMSO+CHIR, DMSO+XAV, TCE, TCE+CHIR and TCE+XAV groups(TCE at the concentration of 1, 10 and 100 ppb, with the DMSO as control; DMSO: Dimethyl suldoxide; CHIR: CHIR-99021, Wnt agonist; XAV: XAV-939, Wnt antagonist), 60 embryos per group. Zebrafish embryos were fed in systematic aquaculture water, 28℃. The water was replaced every 24 h and drugs were added according to the grouping scheme. The cardiac tissues were dissected and analyzed by transcriptome microarray after RNA extraction. The expressions of Wnt signaling pathway related genes were verified by q-PCR. Wnt atagonist XAV and activator CHIR were used alone or in combination to further evaluate the possibility of the Wnt signaling participating in the cardiac developmental toxicity induced by TCE.@*RESULTS@#Compared with control, Zebra fish embryos exposed to TCE showed a significant increase in heart defects, and the main phenotypes were abnormal atrioventricular ratio, looping defects and pericardial edema. The results of microarray profiling showed that the expressions of genes related to Wnt signaling pathway were affected significantly. The results of qPCR further confirmed that TCE inhibited the expressions of Wnt pathway target genes Axin2, Sox9b and Nkx2.5(P＜0.05). Wnt agonist CHIR reduced the TCE-induced cardiac malformation rate significantly, while the addition of Wnt antagonist XAV markedly enhanced the cardiac developmental toxicity of TCE.@*CONCLUSION@#Exposure to TCE leads to heart malformation in zebrafish embryos. Wnt signaling pathway may be involved in the cardiac developmental toxicity induced by TCE.
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Animals , Gene Expression Regulation, Developmental , Heart , Embryology , Transcriptome , Trichloroethylene , Wnt Signaling Pathway , ZebrafishABSTRACT
OBJECTIVE: To study the gene sequence characteristics of hantavirus in Heilongjiang Province in order to find out the reasons for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang Province in recent years.METHODS: Totally 110 rat lung specimens,121 blood specimens from patients diagnosed with mild or atypical HFRS and 100 blood specimens from patients diagnosed with typical HFRS in the First Affiliated Hospital of Harbin Medical University and the Seventh Hospital of Qiqihar City from 2005 to 2015 were collected. The gene sequences were obtained by nucleic acid extraction, RT-NestPCR, and gene sequencing. Explore the possible reasons for the changes in clinical characteristics of HFRS by comparing the obtained sequences with previous strains, homology analysis, building phylogenetic trees of M gene, and finding out the law of nucleotide and amino acid loci changes. RESULTS: TM gene of twenty-six mild or atypical HFRS patients were successfully amplified, including 14 cases of HTN type and 12 cases of SEO type; M gene of twenty-two typical HFRS patients were amplified, including 19 cases of HTN type and 3 cases of SEO type. Compared with the standard strain 76-118, the nucleotide homology of hantavirus from mild or atypical HFRS patients, typical HFRS patients and mice was 74.4%-89.2%, 87.4%-90.3% and 88.1%-88.5%. Comparing hantavirus gene sequence from mice and from patients, the nucleotide homology was 79.7-99.1%. Hljh38 and Hljh39 from patients were significantly different from the other strains. They were the same subtype as Amur virus because they had high homology with Amur strains H5 and H8205(94.9%-97.6%). The deduced amino acids showed some variations compared with the standard strains, but no obvious variation law was observed. CONCLUSION: The reason for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang province is related to the change of viral type. There are also variations of hantavirus and amino acid, but the relationship between specific variation law and clinical manifestations needs to be further verified.
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<p><b>OBJECTIVE</b>To investigate the efficiency of inducing CIK from peripheral blood mononuclear cells(PBMNC) by using immune cell serum replacement(immune cell SR), so as to provide a new strategy for the industrialized production of immune cells.</p><p><b>METHODS</b>The PBMNC of healthy volunteers were collected, and these cells were thawed after short-term cryopreservation and cultured to induce CIK cells. The cells viability was measured by trypan blue exclusion, the phenotypes were analyzed by flow cytometry, and the cytotoxicity was determined by Calcein-AM/PI double staining.</p><p><b>RESULTS</b>In cryopreserved PBMNC, the control group cells failed to normally proliferate. Cell proliferation ratio was low in 2% SR group in comparison with the fresh group, and the difference was significant (P<0.05), however, differences were not statistically significant between 5% SR and fresh group or between 10% AP and fresh group. CD3, CD3CD8 and CD3CD56 cell subsets were not significantly different before and after cryopreservation (P>0.05). After being cultured, CD3, CD3CD4, CD3CD8, CD3CD56 and CD3CD56 subsets and the cytotoxicity in vitro were not significantly different among all group(P>0.05).</p><p><b>CONCLUSION</b>5% SR without the protein of animal origin can be safely used as a substitute for autologous plasma in CIK induced from cryopreserved PBMNC by culture, thus providing a basis for the application of cryopreservation technique of immune cells to cell therapy.</p>
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Humans , Cell Proliferation , Cell Survival , Cryopreservation , Cytokine-Induced Killer Cells , Flow CytometryABSTRACT
Objective To establish the UPLC fingerprint for effective quality control and scientific evaluation of Picrorhiza scrophulariiflora. Methods The analysis was performed on Waters ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm), using acetonitrile-0.5% glacial acetic acid aqueous solution as mobile phase for gradient elution, with the flow rate at 0.3 mL/min, the column temperature at 32 ℃, and the detection wavelength at 295 nm. Total of 25 batches of P. scrophulariiflora and its adulterants were analyzed. Similarity evaluation combined with hierarchical clustering analysis (HCA) and principal components analysis (PCA) were used to evaluate the quality of herbs from different batches. Ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used for qualitative analysis in the positive and negative ion modes. Results There were significant differences in fingerprint chromatogram among P. scrophulariiflora and its adulterants. There were 16 common peaks in UPLC fingerprint of 22 batches of P. scrophulariiflora, and 12 peaks among which were carried out for chemical components identification with the similarity at 0.939-0.998. Twenty-two samples could be classified into three clusters. The PCA result was consistent with that of HCA. The four symbolic compounds in samples were verified by PLS-DA analysis, which identified that No.1, 12, 9 peaks were picroside I, picroside III, and scrophenoside C. Conclusion The establishment of UPLC fingerprint and the recognition of chemical pattern of P. scrophulariiflora can provide a more comprehensive reference for the quality control of herbs.
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<p><b>OBJECTIVE</b>To investigate the clinical effect of internal fixation with closed reduction and hollow compression screws for the treatment of femoral neck fracture in young and middle-aged patients.</p><p><b>METHODS</b>From June 2013 to December 2016, 33 young and middle-aged patients with femoral neck fractures were treated with hollow compression screws fixation including 17 males and 16 females with an average age of 38.5 years old ranged from 19 to 59 years old; 20 cases were on the left side and 13 cases on the right side;the time from injury to operation ranged from 2 to 5 days with an average of 3 days. According to Garden classification, 1 case were type I, 11 cases were type II, 18 cases were type III, 3 cases were type IV. During regular follow-up after operation, through the hip joint X-ray, the healing situation of bone and osteonecrosis were observed. The Harris score was used to evaluate the hip function of the final follow-up.</p><p><b>RESULTS</b>The operation time was from 30 to 50 minutes, the blood loss during operation was 20 to 70 ml. All patients were followed up for 8 to 42 months with an average of 24 months. At the final follow-up, the Harris score of hip joint was excellent in 18 cases, good in 10 cases, fair in 2 cases and poor in 3 cases. Among them, the pain scores were 40.61±5.08, function scores were 38.94±6.78, malformation scores were 3.88±0.69, motion range scores were 3.70±0.64 and the total scores were 87.12±11.98. Thirty cases achieved bone healing, the healing time was 4 to 12 months with an average of 7.5 months, 2 patients occurred with nonunion (Garden type IV), 1 patient with femoral head necrosis (Garden type IV). All patients had no postoperative infection, internal fixation loosening, refracture and other complications.</p><p><b>CONCLUSIONS</b>In treating the young and middle-aged patients with femoral neck fracture, closed reduction and hollow compression screw fixation has advantages of simple, stable fixation, less trauma, high rate of fracture healing, osteonecrosis of the femoral head with low risk and satisfactory clinical effect.</p>
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Due to the characteristics of propofol of high time-varying, and complex compartment model, the traditional method of nonlinear mixed effects modeling (NONMEM) has miscellaneous of variables and plenty of artificial factors in the estimation of propofol. This study was aimed to build a propofol prediction model based on the differential evolution (DE) algorithm and grey model. DE was used to optimize the pa-rameter of multi-variable grey model (MGM) and to build a model of prediction of the plasma concentration of propofol based on the grey model. It was compared with the results of NONMEM algorithm. In conclusion, the median performance error (MDPE) of DE-MGM was -4.6%, while the result of NONMEM is -12.13%. The median absolute performance error (MDAPE) of GA-BP neural network is 13.19%, while that of NONMEM is 23.12%. The experimental results suggest that the new method is suitable to determine the short half-life of anesthesia drug propofol with higher accuracy.
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Objective To observe the effect of curcumin on proliferation, apoptosis, Caspase-3 activity and telomerase activity of chronic granulocytic breast cancer SKBR3 cell line, and to investigate the mechanism of curcumin. Methods The cell growth curve was drawn by MTT;the apoptotic cells were detected by Annexin, V and PI double staining; the expression of Caspase-3 was detected by Westernblot; the activity of telomerase was detected by TRAP-PCR silver staining. Results Curcumin could significantly inhibit the proliferation of SKBR3 cells in a time and concentration dependent, has a certain effect on reducing the telomerase activity of SKBR3 cells can enhance the expression of Caspase-3 induced apoptosis. Conclusion Curcumin can effectively inhibit the proliferation of SKBR3 cells, increase the synthesis of Caspase-3 protein, inhibit the activity of telomerase and mediate the apoptosis of SKBR3 cells.
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Objective To observe the effect of curcumin on proliferation, apoptosis, Caspase-3 activity and telomerase activity of chronic granulocytic breast cancer SKBR3 cell line, and to investigate the mechanism of curcumin. Methods The cell growth curve was drawn by MTT;the apoptotic cells were detected by Annexin, V and PI double staining; the expression of Caspase-3 was detected by Westernblot; the activity of telomerase was detected by TRAP-PCR silver staining. Results Curcumin could significantly inhibit the proliferation of SKBR3 cells in a time and concentration dependent, has a certain effect on reducing the telomerase activity of SKBR3 cells can enhance the expression of Caspase-3 induced apoptosis. Conclusion Curcumin can effectively inhibit the proliferation of SKBR3 cells, increase the synthesis of Caspase-3 protein, inhibit the activity of telomerase and mediate the apoptosis of SKBR3 cells.
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In recent years, global natural disasters have been frequent and resulted in great casualties and property loss. Since Wenchuan earthquake, the disaster emergency rescue system of China has obtained considerable development in various aspects including team construction, task scheduling, personnel training, facilities and equipments, logistics, etc. On April 25, 2015, an earthquake that measured 8.1 on the Richter scale attacked Nepal. Chinese government firstly organized a medical team, named China Medical Team, and sent it to the attacked region in Nepal to implement medical rescue. The medical team completed the rescue mission successfully and creatively based on their experiences.
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Melamine in combination with cyanuric acid has been considered to be more toxic than either melamine or cyanuric acid alone. The objective of this study was designed to evaluate the combined genotoxicity and cytotoxicity of melamine (M) and cyanuric acid (C) at three mass ratios (1:1, 1:2, 2:1). MC (1:1), MC (1:2), and MC (2:1) were evaluated for their potential genotoxic risk, at gene level by Ames test, and at chromosomal level by micronucleus test. In order to evaluate cytotoxicity in HEK-293 cells, the MTT assay was included. Western blot was also employed to investigate the renal injury molecule-1 (Kim-1) expression in HEK-293 cells exposed to MC. Neither genotoxicity at gene level nor at chromosomal level was observed for MC (1:1), MC (1:2), and MC (2:1). Based on MTT assay, three ratios of MC at 82.5 and 165 µg/mL slightly inhibited viability of HEK-293 cells (P<0.05). MC (1:1) at 41.25 and 82.50 µg/mL could elevate the Kim-1 expression in HEK-293 cells.
Subject(s)
Humans , Cell Survival , HEK293 Cells , Hepatitis A Virus Cellular Receptor 1 , Membrane Glycoproteins , Metabolism , Receptors, Virus , Metabolism , Triazines , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of total flavonoids of epimedium (TFE) on the streptozocin (STZ)-induced kidney injury in diabetic rats and discuss the possible mechanism.</p><p><b>METHODS</b>Diabetes was produced by a single injection of streptozocin (40 mg/kg, iv) in male SD rats. The rats were randomly divided into three groups (n = 10): control group, model group and TFE group (100 mg/kg, ig). Animals were sacrificed 12 weeks later. The level of blood glucose, blood urea nitrogen (BUN) and creatinine (Cr) as well as the renal index were determined. Detect the specific biochemical of renal tissue: superoxide dismutase (SOD), malondialdehyde (MDA). Use masson staining to observe the morphology of the renal tissue. Immunohistochemistry was employed to determine the protein levels of transforming growth factor-beta1 (TGF-beta1).</p><p><b>RESULTS</b>Compared to control group, the enhancement of blood glucose, renal index, BUN and Cr was found in model group, which was significantly attenuated by treatment with TFE. Meanwhile, elevated MDA level in renal tissue as well as decreased SOD activities in renal tissue were significantly remitted by TFE. Furthermore, TFE decreased the expression of TGF-beta1.</p><p><b>CONCLUSION</b>TFE can evidently relieve renal damage in rats with diabetic nephropathy induced by STZ, which might be related to antioxidation and modulating the expression of TGF-beta1 protein.</p>
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Animals , Male , Rats , Diabetes Mellitus, Experimental , Metabolism , Diabetic Nephropathies , Metabolism , Epimedium , Chemistry , Flavonoids , Pharmacology , Kidney , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>BACKGROUND</b>Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC.</p><p><b>METHODS</b>Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations.</p><p><b>RESULTS</b>Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05).</p><p><b>CONCLUSIONS</b>These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Renal Cell , Allergy and Immunology , Metabolism , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunohistochemistry , Kidney Neoplasms , Allergy and Immunology , Metabolism , Lymphocytes, Tumor-Infiltrating , Allergy and Immunology , Neovascularization, Pathologic , Allergy and Immunology , Metabolism , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
Objective To study the bone biomechanics of the rabbit osteoporosis models induced by dexamethasone sodium phosphate injection (DX) using a combined treatment modality of 99Tc-MDP and GuKangLing.Methods Rabbits were intramuscularly injected with DX (2 mg/kg) twice a week for 6 weeks.The animal osteoporosis model group (Group C) and normal group (Group A) were compared to confirm the model was available.Another control group (Group B),the osteoporosis control group (Group D) were set for the comparison at the end of the experiment.The 99Tc-MDP therapy group (Group E),GuKangLing therapy group (Group F) and 99Tc-MDP plus GuKangLing therapy group (Group G) were included in the study.The treatment lasted for 16 weeks.The bone biomechanics,cytopathology bone histomorphology,bone mineral density (BMD),X-ray,CT,bone scintigraphy and serum bone alkaline phosphatase (BALP)and P (bone gla protein) were chosen as the markers or methods to evaluate the treatment results (excellent,effective and invalid).The analysis of variance (ANOVA) and t-test were used for group comparison analysis.Results Cytopathology result indicated that there was no bone trabecula destruction in Group A.However,there was distinct bone destruction in Group C.The bone biomechanics (left femur head (265.914 ±52.773) N,L4(369.671 ±94.919) N),BMD(left femur (0.238 ±0.016) g/cm2,L4(0.236 ±0.016) g/cm2)and bone histomorphology ( (66.230 ± 10.848) ％ ) in Group C reduced clearly as compared with Group A ((405.343±55.410) N,(750.870±53.718) N,(0.294±0.017) g/cm2,(0.302±0.023) g/cm2,( 131.500 ± 21.846) ％ ) ( t ≥4.550,all P ＜ 0.01 ).Radionuclide bone scan also showed that the uptake of tracers was higher by the main arthrosis in Group C than that in Group A.Vertebra was not clearly visualized on bone scan image.There were significant differences between Group A and Group C in serum BALP and P ((45.000±7.303) vs (12.485 ±1.512) U/L,(0.168±0.018) vs (0.115 ±0.017) μg/L,t =4.126,5.476,both P ＜ 0.01 ),which indicated that the animal osteoporosis model was available.The pathological results showed an improved recovery of bone structure and trabecular in Groups E and G,but a worse recovery in Group F.Biomechanics result in Groups E and G (left femur head (386.457 ±77.077) N and (432.771 ± 17.525) N,L4(649.550 ± 126.859) N and (655.443 ±76.555) N) improved apparently,which were similar to Group B.The radiotracer uptake in Group F was lower than that in group D.The bone biomechanics,bone histomorphology,BMD,serum BALP and P after the treatment showed significant differences in Groups E,F and G (F:8.556 - 31.608,all P＜0.01 ),and the bone biomechanics result in Group G was a little better than that in Group E (t =2.625,P ＜ 0.05 ).The results of Group G and E were considered as excellent,and Group F was considered as effective.Conclusions The treatment of 99Tc-MDP combined with GuKangLing could improve the bone biomechanics of rabbit osteoporosis models and may be a potential method to increase the bone strength for resisting external force.
ABSTRACT
<p><b>OBJECTIVE</b>In China, liver failure is also termed as severe hepatitis in whom chronic severe hepatitis B (CSHB) is most common. The aim of this study was to assess whether CSHB based on different liver injury extent can meet the international definition of acute-on-chronic liver failure(ACLF)criteria, according by their clinical and pathological feature.</p><p><b>METHODS</b>A total of 91 patients with CSHB were involved in the study. The clinical findings, laboratory data and liver pathology features were retrospectively analyzed and grouped by hepatitis virus B carrier state (HBC), chronic hepatitis B (CHB) or liver cirrhosis (LC) before they started liver failure.</p><p><b>RESULTS</b>74 out of the 91 patients were male and 17 were female, the mean age was 40.6+/-11.2 years. 9.9%, 7.7% and 82.4% of the patients were based on HBC, CHB and LC respectively. The ages of HBC group were youngest. The mean age of HBC group (years) (25.8+/-6.6) was significantly lower than that of CHB group (36.9+/-9.0) and LC group (42.0+/-10.5)with P values of 0.032 and 0.001 respectively. Most cases presented with sub-acute liver failure characterized by high icterus and ascites. Predisposing factors included exertion, superinfection, virus variation, drugs or alcoholic injury. No difference found between PTA (F = 0.906, P = 0.408) and TBil (F = 0.839, P = 0.436) among the above three groups. The Alb and CHE levels in LC group were (30.3+/-5.1) g/L and (2926.8+/-1471.1) U/L respectively, which were lower than both HBC group [Alb (35.6+/-5.1) g/L, CHE (4363.5+/-2063.2) U/L] and CHB group [Alb (37.4+/-5.0) g/L, CHE (5167.1+/-1522.1) U/L] (F = 9.450; F = 9.297; P value less than 0.01).The level of CHO (1.8+/-1.0) mmol/L in LC group was lower than that of HBC group (2.9+/-1.0mmol/L, P = 0.034), while serum HBV DNA level of HBC group [(6.8+/-1.7) log10copies/ml] was higher than that of LC group [(4.2+/-2.6) log10copies/ml]. The liver tissue in HBC and CHB group showed massive or submassive necrosis which distribute evenly in different parts of liver and similarly in slides, most like acute/subacute severe hepatitis. The chronic lesion was easily covered by extensive necrosis in CSHB based on CHB, with portal fibrosis can be seen by masson stain. Characteristic picture of LC group were massive or submassive necrosis with some nodules were intact or only patchy necrosis of the parenchyma, disparity of extent and stage of necrosis existed in slides, which were the major difference in histopathological change in HBC and CHB group.</p><p><b>CONCLUSION</b>Most of CSHB cases were based on liver cirrhosis, which match with the international definition of ACLF, while small part of CSHB cases based on HBC and CHB are identical to acute/subacute liver failure.</p>