Multi-functional osteoclasts in matrix-based tissue engineering bone / 中华创伤杂志(英文版)

The repair of bone defects, especially for the large segment of bone defects, has always been an urgent problem in orthopedic clinic and attracted researchers' attention. Nowadays, the application of tissue engineering bone in the repair of bone defects has become the research hotspot. With the rapid development of tissue engineering, the novel and functional scaffold materials for bone repair have emerged. In this review, we have summarized the multi-functional roles of osteoclasts in bone remodeling. The development of matrix-based tissue engineering bone has laid a theoretical foundation for further investigation about the novel bone regeneration materials which could perform high bioactivity. From the point of view on preserving pre-osteoclasts and targeting mature osteoclasts, this review introduced the novel matrix-based tissue engineering bone based on osteoclasts in the field of bone tissue engineering, which provides a potential direction for the development of novel scaffold materials for the treatment of bone defects.

Cellular environment controls the dynamics of histone H3 lysine 56 acetylation in response to DNA damage in mammalian cells

Epigenetic changes play a crucial role in sensing signals and responding to fluctuations in the extracellularenvironment. How the cellular micro-environment affects DNA damage response signalling in chromatincontext is not extensively studied. Histone acetylation is dynamic and very sensitive to changes in theextracellular environment. Existing literature on H3 lysine 56 acetylation (H3K56ac) levels upon DNA damagein mammals presents a conflicting picture. The occurrence of both increased and decreased H3K56ac uponDNA damage in our experiments led us to investigate the role of the micro-environment on H3K56ac. Here,we show that the global levels of H3K56ac increase as cells grow from low density to high density whileSIRT1 and SIRT6 expression decrease. Additionally, rising lactic acid levels increase H3K56ac. Our resultsshow that cell density and accumulation of metabolites affect dynamics of H3K56ac in response to DNAdamage. Upon DNA damage, H3K56ac increases in low density cells with low initial acetylation, whileacetylation decreases in high cell density cells. These results highlight that H3K56ac levels upon DNA damageare dependent on the metabolites in the extracellular milieu which impact chromatin structure by regulatingchromatin modifying enzymes. Accumulation of lactic acid at high cell density reflects conditions similar to thetumour micro-environment. As H3K56ac increases in tumours, lactic acid and low pH might alter H3K56ac intumours, leading to deregulated gene expression, contributing to tumour progression.

Research progress on the risk factors and pathogenesis of climatic droplet keratopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Climatic droplet keratopathy(CDK), an acquired corneal degenerative disease, is characterized by oil droplet deposits and banded opacity in the pre-corneal elastic layer and stroma layer, which can severely affect the visual acuity of patients. Recently, many studies have indicated that various factors caused the occurrence and development of CDK. However, the pathogenesis and specific pathogenesis of the disease remain unclear. So this article aims to summarize four aspects of the CDK, including the epidemiological characteristics, the morphology of corneal lesions, the composition of corneal deposits and the ocular surface micro-environment, and then provide a reference for ophthalmologists to acknowledge and explore CDK deeply.

Effects of oxygen-enriched negative pressure wound therapy in improving wound microenvironment to tissue proliferation and vascularization / 医学研究生学报

ObjectiveIt is indefinited that oxygen-enriched negative pressure wound therapy, namely negative pressure wound therapy combined with topical oxygen therapy (NPWT+TOT), improve the effects of wound microenvironment in tissue proliferation and vascularization. The objective is to discuss effects of oxygen-enriched negative pressure wound therapy in improving wound microenvironment to tissue proliferation and vascularization.MethodsTo select sixty-four patients in the outpatient wound care center of the eastern theater general hospital from January to October, 2019, which were randomly divided into the experimental group (NPWT+TOT) and the control group (NPWT), 32 cases in each group. The patients were treated with oxygen-enriched negative pressure wound and negative pressure wound respectively for 2 weeks to observe the changes of wound temperature and PH before and during intervention. Bacterial culture and immunohistochemical staining which were made from wound secreta and wound bed tissues to observe bacterial culture results, tissue proliferation activity and microvascular density before intervention and 14 days after intervention. After the intervention, the patients were treated by standard wet therapy and followed up to wound healing or 3 months after the intervention to observe the wound healing rate and wound healing time.ResultsAfter two weeks' continuous intervention, wound temperature of patients increased and PH value decreased significantly between the experimental group and the control group. Meanwhile, the intervention group was more effective, and there were significant differences between the two groups (P<0.05). The positive rate of bacterial culture after intervention in the experimental group and the control group was 26.67% and 41.38% respectively, with no statistically significant difference (P=0.233). Compared with the control group, the increase of tissue activity and microvascular density in the experimental group was more significant (P<0.05). After three months' follow-up, the wound healing rate of the experimental group was increased by 12.5% compared with the control group, and the average wound healing time was shortened by 9.2 days.ConclusionOxygen-enriched negative pressure wound therapy can improve wound microenvironment, reduce the positive rate of wound bacterial culture, improve the proliferation activity of wound tissue and degree of vascularization, and promote wound healing.

Application of three-dimensional cell model in tumor research / 中国药科大学学报

@#The three-dimensional cell model cultures different types of cells in vitro. By means of special materials or carriers, the cells can grow, migrate and differentiate in a three-dimensional environment. The three-dimensional cell model provides the cells with an in vitro environment that is close to in vivo, making the gene expression and signal exchange of the cells more physiologically relevant. This paper starts with the concept and classification of three-dimensional cell model, then summarizes the applications and progresses of three-dimensional cell model in tumor micro-environment, cancer metastasis and anti-tumor drug development in recent years. Based on the current shortcomings of the three-dimensional cell model, this paper presents the assumptions and prospects for the application of three-dimensional cell model in tumor therapy.

Interaction between vaginal micro-environment alterations and HPV16 infection in cervical intraepithelial neoplasia / 中华流行病学杂志

Objective To explore the effect of vaginal micro-environment alterations and HPV1 6 infection and their interaction in the progression of cervical intraepithelial neoplasia.Methods The participants of this study came from the cervical lesions study cohort in Shanxi province,including 623 women with normal cervical (NC),303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and 93 patients with pathogenieally diagnosed high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ).The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected,and HPV16 infection were detected by using flow-through hybridization technology and H2O2,β-glucuronidase,clotting enzyme,neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis.pH value and vaginal cleanliness were also detected at the same time.The database was established and analyzed by SPSS statistical software (version 22.0).Results The HPV16 infection rate (trend x2=55.45,P＜0.001) and the abnormal rates of H2O2 (trend x2 =26.19,P＜0.001),pH (trend x2=5.06,P=0.024),vaginal cleanliness (trend x2=19.55,P＜0.001),β-glucuronidase (trend x2 =17.52,P＜0.001) and neuraminidase (trend x2 =14.90,P＜ 0.001) increased gradually along with the severity of cervical intraepithelial neoplasia,but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend.The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H2O2,β-glucuronidase,clotting enzyme and neuraminidase in CIN Ⅰ group,and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness,H2O2,β-glucuronidase and neumminidase in CIN Ⅱ/Ⅲ group.Conclusion Our findings indicated that the vaginal micro-environment alterations and HPV1 6 infection could increase the risk of cervical intraepithelial neoplasia,and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.

Interaction between vaginal micro-environment alterations and HPV16 infection in cervical intraepithelial neoplasia / 中华流行病学杂志

Objective To explore the effect of vaginal micro-environment alterations and HPV1 6 infection and their interaction in the progression of cervical intraepithelial neoplasia.Methods The participants of this study came from the cervical lesions study cohort in Shanxi province,including 623 women with normal cervical (NC),303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and 93 patients with pathogenieally diagnosed high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ).The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected,and HPV16 infection were detected by using flow-through hybridization technology and H2O2,β-glucuronidase,clotting enzyme,neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis.pH value and vaginal cleanliness were also detected at the same time.The database was established and analyzed by SPSS statistical software (version 22.0).Results The HPV16 infection rate (trend x2=55.45,P＜0.001) and the abnormal rates of H2O2 (trend x2 =26.19,P＜0.001),pH (trend x2=5.06,P=0.024),vaginal cleanliness (trend x2=19.55,P＜0.001),β-glucuronidase (trend x2 =17.52,P＜0.001) and neuraminidase (trend x2 =14.90,P＜ 0.001) increased gradually along with the severity of cervical intraepithelial neoplasia,but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend.The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H2O2,β-glucuronidase,clotting enzyme and neuraminidase in CIN Ⅰ group,and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness,H2O2,β-glucuronidase and neumminidase in CIN Ⅱ/Ⅲ group.Conclusion Our findings indicated that the vaginal micro-environment alterations and HPV1 6 infection could increase the risk of cervical intraepithelial neoplasia,and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.

Mechanisms involved in liver metastasis of breast cancer / 实用肿瘤学杂志

Liver is the common metastatic site of breast cancer .The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver micro -environment .In this re-view,we reviewed the molecular(including the connection of proteins ,protein kinases,miRNAs),signal transduc-tion pathways(including CXCL12-CXCR4 axis,Wnt/beta-catenin signaling pathway,AF1q/TCF7/CD44 regu-latory axis,laminin receptor/Akt/ERK signaling pathway,leptin/ERK/IL-8 signaling pathway)and the influen-cing factors(including hypoxia inducible factors,tumor-associated fibroblasts,adipose tissue matrix stem cells, metalloproteinases,selective ligands,inflammatory cell infiltration)associated with the liver micro -environment in breast cancer .

Cancer research in need of a scientific revolution: Using ‘paradigm shift’ as a method of investigation.

Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of ‘paradigm shift’ as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the ‘paradigm shift’ method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the ‘paradigm shift’ method to produce perspective reversals consistent with current experimental evidence. The ‘paradigm shift’ method enlightens the existence of a tumour physiologic–prophylactic–pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The ‘paradigm shift’ method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy.

Effect of Activating Blood to Resolve Stagnation on Cells Expressing CD34 and Vascular Endothelial Growth Factor in Rats with Acute Myocardial Infarction / 中国康复理论与实践

@#Objective To explore the effect of Activating Blood to Resolve Stagnation on the expression of CD34 and vascular endothelial growth factor (VEGF) in rats with acute myocardial infarction. Methods 32 Sprague-Dawley rats were randomly divided into sham operation group (A, n=8), model group (B, n=8), Xuesaitong Injection + granulocyte colony- stimulating factor (G- CSF) group (C, n=8) and G-CSF group (D, n=8). Corresponding medicine was given to each group 3 hours after modeling, for 6 days. Pathomorphological changes were observed through HE staining, and the expression of CD34, VEGF and Ki-67 were observed through immunohistochemical staining. Results The expressions of CD34, VEGF and Ki-67 were higher in groups B, C and D than in group A (P<0.05), and were higher in group groups C and D than in group B (P<0.05). The expressions of CD34 and VEGF were higher in group C than in group D (P<0.05). However, there was no significant difference in the expression of Ki-67 between 2 groups (P>0.05). Conclusion The expression of CD34 and VEGF increases with Activating Blood to Resolve Stagnation method, which is superior to using G-CSF only. Activating Blood to Resolve Stagnation may play an important role in the treatment of acute myocardial infarction.

Effect of Activating Blood to Resolve Stagnation on Cells Expressing CD34 and Vascular Endothelial Growth Fac-tor in Rats with Acute Myocardial Infarction / 中国康复理论与实践

Objective To explore the effect of Activating Blood to Resolve Stagnation on the expression of CD34 and vascular endotheli-al growth factor (VEGF) in rats with acute myocardial infarction. Methods 32 Sprague-Dawley rats were randomly divided into sham opera-tion group (A, n=8), model group (B, n=8), Xuesaitong Injection + granulocyte colony-stimulating factor (G-CSF) group (C, n=8) and G-CSF group (D, n=8). Corresponding medicine was given to each group 3 hours after modeling, for 6 days. Pathomorphological changes were observed through HE staining, and the expression of CD34, VEGF and Ki-67 were observed through immunohistochemical staining. Re-sults The expressions of CD34, VEGF and Ki-67 were higher in groups B, C and D than in group A (P0.05). Conclusion The expression of CD34 and VEGF in-creases with Activating Blood to Resolve Stagnation method, which is superior to using G-CSF only. Activating Blood to Resolve Stagna-tion may play an important role in the treatment of acute myocardial infarction.

Expressions of transforming growth factor-β1 and interleukin 6 mRNA and protein in bone of rats with chronic fluorosis / 中华地方病学杂志

Objective To investigate the significance of osteo-immunology related factor transforming growth factor-β1 (TGF-β1) and interleukin 6 (IL-6) in bone of rats with chronic fluorosis.Methods Thirty-six healthy SD rats were divided to three groups according to body weight with the method of random digits table.The rats of control were fed with tap water(NaF ＜ 1 mg/L) and the experimental rats were exposed to NaF (lower dose group:5 mg/L,higher dose group:50 rmg/L) added to the drinking water to establish the chronic fluorosis model.All rats were killed on the six months and the metaphysic of femoral was collected.Bone fluorine was detected by ashing-fluorin ion selective electrode method.Bone tissues were stained with hematoxylin-eosin and observed under optical microscope.The content of bone alkaline phosphatase (BALP) in rat serum was detected by enzyme-linked immunosorbent assay(ELISA).The expressions of TGF-β1 and IL-6 mRNA and protein in bone were detected by in situ hybridization (ISH) and immunohistochemistry (IHC).Results The contents of bone fluorine were increased gradually in the control,the lower and higher doses fluoride groups[(306.04 ± 12.57),(652.91 ± 51.83),(1 094.11 ± 91.41)mg/kg,F =31.14,P ＜ 0.05].Bone sclerosis could be observed under optical microscope in lower and higher dose groups.The content of BALP in serum increased with the dose of fluoride gradually in the control,the lower and higher doses fluoride groups[(27.78 ± 4.09),(46.59 ± 5.75),(57.45 ± 3.99)U/L],expressions of mRNA (111.84 ± 4.62,123.86 ± 7.46,140.83 ± 5.21) and protein (118.60 ± 7.09,133.17 ± 7.33,145.67 ± 9.61) of TGF-β1 were both increased(F =30.29,73,28,33.65,all P ＜ 0.05).The expressions of mRNA(117.78 ± 7.01,119.90 ± 5.10) and protein(122.79 ± 6.49,123.81 ± 7.99) of IL-6 were both higher than those of the control (106.49 ± 6.76,112.11 ± 5.80,F =15.47、10.83,all P ＜ 0.05).Conclusion The expressions of osteo-immunology related factor TGF-β1 and IL-6 in bone of rats with chronic fluorosis have changed,which indicates that fluoride can impact the increased bone formation by regulating the micro environment of bone.

Production of IFN-gamma by TNF-alpha in Macrophages from Tumor Micro Environment; Significance in Angiogenic Switch Control

BACKGROUND: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-alpha. Recently, macrophage also can produce the INF-gamma that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-alpha can modulate the INF-gamma production in the macrophages from tumor environment as a part of tumor angiogenic switch. METHODS: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. Mac1(+) -macrophages were purified using magnetic bead (MACs(TM); Milteny Biotech, Germany) and cultured with various concentrations of TNF-alpha for various time points at 37degreeC. The supernatants were analyzed for IFN-gamma or VEGF by ELISA kit (Endogen, Woburn, MA). RESULTS: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-alpha to produce INF-gamma. However, the cells from tumor environment produced IFN-gamma as well as VEGF and upregulated by the addition of LPS or TNF-alpha. RT-PCR analysis revealed the external TNF-alpha-induced IFN-gamma gene expression in the macrophages from tumor environment. CONCLUSION: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-alpha might be a key cytokine in tumor angiogenic switch.