ABSTRACT
ObjectiveBased on the protective effect of Dengzhan Shengmai capsules （DZSM） on chronic cerebral hypoperfusion （CCH）， network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group， model group， ginaton group （48 mg·kg-1）， DZSM low- and high-dose groups （0.040 5， 0.162 g·kg-1）. The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem， GeneCards， Metascape and other databases were used for targets collection and enrichment analysis. Besides， the association of ingredients targets of DZSM with disease targets of CCH， core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment， the crossing times， time spent in the target quadrant， movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， cytokine-cytokine receptor interaction， tumor necrosis factor （TNF） signaling pathway， blood circulation， angiogenesis， extracellular matrix and other related biological processes and pathways， and acting as targets such as interleukin-6 （IL-6）， TNF， insulin-like growth factor 1 （IGF1）， vascular endothelial growth factor A （VEGFA）， epidermal growth factor （EGF）. The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH， and its multi-component， multi-pathway， multi-target mechanism is also revealed， which provides a basis for further study of the mechanism.
ABSTRACT
Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.
Subject(s)
Humans , Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Research Design , Signal TransductionABSTRACT
Ischemic stroke is the most common form of stroke and one of the main diseases leading to death and disability in the world. Its pathological process is complex and changeable as a result of the interaction of multiple pathological links, such as oxidative stress, apoptosis and inflammation. Traditional Chinese medicine Notoginseng Radix et Rhizoma is the dried roots and rhizomes of Panax notoginseng. In clinic, it is mainly used for the treatment of diseases of cardio-cerebral system and vascular system. Recent studies have shown that total saponins of P. notoginseng, the main active ingredients of P. notoginseng against cerebral ischemia, are complex, and can interfere with the enzyme-promoted cascade reaction through multiple pathways, multiple links and multiple targets, so as to exert its physiological effect. Therefore, it has become a hotspot in studies for prevention and treatment of cerebral ischemia. At present, a great advance has been made in studies on the mechanism of anti-cerebral ischemia of P. notoginseng saponins, but more in-depth studies are needed because of its complex mechanism. Therefore, in this paper, a total of 165 kinds of P. notoginseng saponins were summarized, and simply divided into protopanaxadiol saponins(55 species), protopanaxadiol saponins(37 species) and special structural type saponins(73 species) according to their structural types, so as to provide reference for further studies of P. notoginseng saponins. In addition, the effect of P. notoginseng on cerebral ischemia is clear, but its mechanism remains to be further explored. This paper summarizes the mechanism of P. notoginseng saponins against cerebral ischemia in five aspects: antioxidant stress, reduction of apoptosis, reduction of inflammatory reaction, inhibition of calcium overload and protection of blood-brain barrier. Four kinds of drugs commonly used in the treatment of cerebral ischemia were summarized, in order to provide a theoretical basis for further development and utilization of P. notoginseng saponins in the treatment of cerebral ischemia.
Subject(s)
Humans , Brain Ischemia , Cerebral Infarction , Panax notoginseng , Rhizome , SaponinsABSTRACT
Objective::Based on the protective effect of Guhong injection (GH) on cerebral ischemia, mechanism of GH against cerebral ischemia was identified using RNA-seq transcriptome and bioinformation analysis. Method::The model of middle cerebral artery occlusion (MCAO) was established through thread embolization. Sham group, model group, low-dose GH group (0.625 mL·kg-1·d-1), high-dose GH group (2.5 mL·kg-1·d-1), positive group (Ginaton, 8 mL·kg-1·d-1) were set up. Ludmila Belayev 12-point scoring method was applied to assess the protective effect of GH against MCAO-induced cerebral ischemia. And the differentially expressed genes after treatment with GH were identified by RNA-Seq technology. Enrichment analysis, cluster analysis and association analysis on disease targets of cerebral ischemia were carried out through such databases as DAVID, String and The Human Phenotype Ontology. Finally, the regulatory network was constructed by Cytoscape3.4.0. Result::Compared with the sham group, the neurological impairment was obvious in the model group (P<0.01), and the neurological impairment was alleviated in the GH group compared with the model group (P<0.05). RNA-Seq technology analysis showed that GH regulated genes involving such biological processes as cell apoptosis, inflammation, oxidative stress, toll-like signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Twenty disease targets and 64 MAPK signaling pathway genes were associated with differentially expressed genes after GH treatment, in which 23 genes were involved in apoptosis and inflammation. Conclusion::GH protected against cerebral ischemia in many ways, among which MAPK signaling pathway is an important way to exert its effect in inhibiting apoptosis and inflammation.
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With the progress and development of the DNA test and imaging technique, and the evolution of evidence rule which bring the discussions about whether the individual identification using imaging data is outdated, and other disputes such as whether radiologic evidence could be suitable for contemporary evidence and be used to solve the posture difference of imaging test. This article summaries the domestic and foreign researches of individual identification using imaging data in the past 20 years and reviews the problems above.
Subject(s)
Humans , DNA/analysis , Forensic Genetics/standardsABSTRACT
Erbin, a member of Leucine-rich repeat and PDZ-containing protein family, was found to inhibit TGF-β-induced epithelial-mesenchymal transition (EMT) in our previous study. However, the mechanism of Erbin in regulating EMT is unclear. Semaphorin protein Sema4C, with PDZ binding site at C-terminal has been recognized as a positive regulator of EMT. Here, we aimed to examine the interaction between Erbin and Sema4C. HK2 cells were treated with TGF-β1, or transfected with Erbin and (or) Sema4C. Interaction of Erbin and Sema4C was identified by immunoprecipitation. RT-PCR was used to detect the expression of Erbin and Sema4C at mRNA level after transfection. The expression levels of Erbin, Sema4C, and markers of EMT were measured by using Western blotting or ELISA. After HK2 cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the protein expression levels of Erbin and Sema4C were both up-regulated, and immunoprecipitation results showed Erbin interacted with Sema4C in HK2 cells both at endogenous and exogenous levels. Furthermore, overexpression of Sema4C suppressed E-cadherin, induced vimentin and promoted fibronectin secretion, indicating Sema4C promotes the process of EMT. However, HK2 cells overexpressing Erbin were resistant to Sema4C-induced EMT. In contrast, Erbin specific siRNA promoted EMT induced by Sema4C. Taken together, these results suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced EMT.
ABSTRACT
Erbin, a member of Leucine-rich repeat and PDZ-containing protein family, was found to inhibit TGF-β-induced epithelial-mesenchymal transition (EMT) in our previous study. However, the mechanism of Erbin in regulating EMT is unclear. Semaphorin protein Sema4C, with PDZ binding site at C-terminal has been recognized as a positive regulator of EMT. Here, we aimed to examine the interaction between Erbin and Sema4C. HK2 cells were treated with TGF-β1, or transfected with Erbin and (or) Sema4C. Interaction of Erbin and Sema4C was identified by immunoprecipitation. RT-PCR was used to detect the expression of Erbin and Sema4C at mRNA level after transfection. The expression levels of Erbin, Sema4C, and markers of EMT were measured by using Western blotting or ELISA. After HK2 cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the protein expression levels of Erbin and Sema4C were both up-regulated, and immunoprecipitation results showed Erbin interacted with Sema4C in HK2 cells both at endogenous and exogenous levels. Furthermore, overexpression of Sema4C suppressed E-cadherin, induced vimentin and promoted fibronectin secretion, indicating Sema4C promotes the process of EMT. However, HK2 cells overexpressing Erbin were resistant to Sema4C-induced EMT. In contrast, Erbin specific siRNA promoted EMT induced by Sema4C. Taken together, these results suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced EMT.
Subject(s)
Humans , Adaptor Proteins, Signal Transducing , Genetics , Metabolism , Blotting, Western , Cadherins , Metabolism , Cell Line , Epithelial-Mesenchymal Transition , Immunoprecipitation , Kidney Tubules, Proximal , Cell Biology , Metabolism , Protein Binding , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Semaphorins , Genetics , Metabolism , Transfection , Transforming Growth Factor beta1 , Pharmacology , Vimentin , MetabolismABSTRACT
OBJECTIVE@#FTIR (Fourier transform infrared) spectroscopy was applied to observe the process of postmortem degradation in rats' cardiac muscle and provided a new method for the estimation of post-mortem interval (PMI).@*METHODS@#The rats were sacrificed by cervical dislocation and the bodies were kept in a controlled environmental chamber set at (20 +/- 2) degrees C. The FTIR spectra was applied to measure the changes of different chemical group from rats' left ventricle muscle at the different time point postmortem.@*RESULTS@#There were not obvious changes for the main FTIR absorbance peaks. But the different FTIR absorbance at the wave-number (cm(-1)) indicated the three types: increase, decrease, stable. The various absorbance ratios also demonstrated the similar changes.@*CONCLUSION@#FTIR spectroscopy may be potentially used as an effective method for estimating PMI in forensic practice using cardiac muscle tissue.
Subject(s)
Animals , Male , Rats , Autopsy , Fatty Acids/metabolism , Forensic Pathology , Models, Animal , Myocardium/metabolism , Nucleic Acids/metabolism , Postmortem Changes , Rats, Sprague-Dawley , Spectroscopy, Fourier Transform Infrared/methods , Time FactorsABSTRACT
With the development of the cross-correlation technique in surgery, the transplantation and vi-cariousness have become more and more important in repair surgery and reconstructive surgery. A nice bio-material could replace the related tissue or organ of human body, support the homologous function of organ-ism,and accelerate the process of self recovery and autotherapy. This review is about the status of research and application of biomaterial in surgery.
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OBJECTIVE@#To establish a database of high-fall death cases for future forensic study and practice, based on the scene investigation, injury characteristics and other informations.@*METHODS@#Five hundred and four cases of high-fall death from 5 provinces and cities were included in the study. Data including personal information of the deceased, scene investigation, autopsy findings, history of mental illness and the results of toxicology were collected and analyzed.@*RESULTS@#The male accidental death rate was significantly higher than that of female. No case of suicide was found in the 0-10 age group, while the suicide rate was apparently higher in the 60 years or over age group than that of accident. Most of the accident cases occurred at workplace, with head landing first and foot or lower-extremity landing first observed from height below 10 m and between 10-25 m, respectively.@*CONCLUSION@#The majority of cases have obvious conclusions. A substantial set of the cases, however, is still difficult to determine the mechanism of injury and the manner of death. So further study should be performed.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Accidental Falls , Age Distribution , Cause of Death , Forensic Pathology , Homicide/statistics & numerical data , Retrospective Studies , Sex Distribution , Suicide/statistics & numerical data , Wounds and Injuries/pathologyABSTRACT
This is a study to evaluate the biomechanical properties of porcine trachea; the intention is to provide experimental methods as well as evidence for further studies on human trachea and artificial trachea. In the current study, the biomechanical indices such as bending stiffness, radial pedestal and stress-straining, bursting strength, and residual stress were adopted. The findings were as follows: there is residual stress in the trachea; when the 50mm trachea is compressed 50%, the force of radial pedestal is about 10N; the force of break from cricoid to eminence is from 180mmHg to 110mmHg. Meanwhile, the data of bent are gained and the curve of stress-straining is depicted. Rresidual stress exists in porcine trachea, and trachea membrane disrupts with the increasing of endotracheal pressure; meanwhile, the porcine trachea possesses fine properties such as radial pedestal, bending and elongation.
Subject(s)
Animals , Female , Male , Biomechanical Phenomena , Elasticity , Pressure , Stress, Mechanical , Swine , Tensile Strength , Trachea , PhysiologyABSTRACT
A nice biomaterial,which could replace the correlated tissue or organic of human body,supports the homologous function of organism,and accelerates the process of self recovery and autotherapy in the same time.The application of biomaterial in clinic,not only have the chemical characters and function of vitodynamics to match,but also be with nice biocompatibility and practical safety.Some development of biomaterial and the biocompatibility of it in this paper was reviewed,and the application status in the cardiothoracic surgery in recent years.