Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes / 器官移植

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

Mechanism of Calculus Bovis treating keratitis based on network pharmacology / 中华实验眼科杂志

Objective:To investigate the complex Calculus Bovis-target-keratitis network and to explore the molecular mechanism of Calculus Bovis treating keratitis through network pharmacology. Methods:Genes related to keratitis were searched in the online DisGeNET database and the protein-protein interaction (PPI) network of keratitis-associated proteins was constructed.The components isolated and identified in Calculus Bovis were collected through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, https: //tcmsp-e.com/tcmsp.php), Chemistry Database by Shanghai Institute of Organic Chemistry of CAS (http: //www.organchem.csdb.cn), and published literature.The canonical SMILES information of the collected components was exported, which were submitted to the SwissTargetPrediction platform to predict potential targets of the components.The active component-predicted target network of Calculus Bovis was constructed and merged with the PPI network of keratitis-associated proteins to build the active component-potential target network of Calculus Bovis and systemically investigate the potential targets and signal pathways of Calculus Bovis in treatment of keratitis.The component-target-pathway network was established to analyze the mechanism of Calculus Bovis treating keratitis. Results:Thirty-nine components isolated and identified in Calculus Bovis were searched and 65 target genes related to keratitis were screened.Of the 28 potential targets involved in Calculus Bovis treating keratitis, there were 7 direct targets, including tumor necrosis factor, caspase 1, Toll-like receptor 9, C-X-C motif chemokine ligand 8, interleukin-6, mitogen-activated protein kinase 8, neurotrophic receptor tyrosine kinase 1.The 28 potential targets were annotated to 12 entries for biological process, 18 for cellular components and 13 for molecular function.In the Kyoto encyclopedia of genes and genomes pathway enrichment analysis, 10 signal pathways were identified as enriched categories, which were mainly related to human cytomegalovirus infection, amoebiasis, antifolate resistance, PI3K-Akt signaling pathway, rheumatoid arthritis, apoptosis, cytokine-cytokine receptor interaction, malaria, non-alcoholic fatty liver disease, interleukin-17 signaling pathway. Conclusions:Calculus Bovis may play an adjuvant therapeutic effect on keratitis through anti-inflammatory, antibacterial, antiviral, immune regulation, inflammatory regulation and other functions.

Progress of unfolded protein response in acute respiratory distress syndrome / 国际儿科学杂志

Acute respiratory distress syndrome(ARDS)is a severe respiratory disease in children and the pathogenesis is not fully defined.It is mainly related to various mechanisms of lung injury such as inflammation and autophagy.In recent years, studies have found that, endoplasmic reticulum stress(ERS)can aggravate lung injury in ARDS, in which protein homeostasis imbalance can induce activation of the unfolded protein response(UPR).The UPR reconstructs homeostasis by mediating transmembrane protein-related signaling pathways, while continuous excessive ERS will promote apoptosis and autophagy.This review summarizes the progress of the signaling pathway of UPR related to lung injury and its inflammatory effect in ARDS.

Research Progress of Macropinocytosis in Digestive System Tumors / 肿瘤防治研究

Macropinocytosis, an evolutionarily conserved, actin-dependent form of endocytosis, is involved in various physiological processes, including nutrient absorption, antigen presentation, and cell signaling transduction and migration. Oncogene activation and tumor suppressor inactivation induce macropinocytosis in tumors in the digestive system, involved in tumorigenesis and progression, whereas the inhibition of macropinocytosis slows the aggressive phenotype of digestive system tumors and improves the efficacy of anti-tumor drugs. Macropinocytosis can also be used as a delivery route for anti-tumor drugs. Therefore, macropinocytosis has been widely studied to develop new methods for the treatment of digestive system tumors.This paper reviews the role of macropinocytosis in the body, the regulation of macropinocytosis-related signaling pathway, as well as the mechanism of macropinocytosis in colorectal cancer, pancreatic ductal adenocarcinoma, liver cancer and other digestive system tumors, to provide reference for related researches.

Research progress on signal pathways related to prevention and treatment of hypertension target organ damage by traditional Chinese medicine / 中国药房

Hypertension is a common cardiovascular disease. At present， the prevalence and mortality of hypertension in China continue to rise， the morbidity and mortality of complications remain high. The continuous increase of blood pressure can cause damage to multiple target organs such as heart， brain， kidney and blood vessels. This article reviews the research progress of signal pathways related to the prevention and treatment of hypertension target organ damage by traditional Chinese medicine， and summarizes six signal pathways related to RhoA/ROCK， renin-angiotensin-aldosterone system， endothelin-1/nitric oxide， transforming growth factor-β1/Smads， phosphatidylinositide 3-kinases/protein kinase B， and Toll-like receptor 4/nuclear transcription factor-κB， in order to provide theoretical evidence for further research on clinical diagnosis and treatment of hypertension and its target organ damage.

Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification / 中国中药杂志

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Effect of expressing of anti-PD-1 antibody in mouse mammary gland on spleen T cells in transgenic mice / 生物工程学报

This study aims to investigate the effect of anti-PD-1 antibody expressed in mouse mammary gland on the surface antigen protein of spleen T cells, cytokine expression, spleen CD4+ T cell proliferation and proliferation related pathways of transgenic mice at the cellular level. Transgenic mice expressing anti-human PD-1 antibody at 8 weeks of age without pregnancy and 18 weeks of age with lactation were divided into two groups, with transgenic negative mice in each group as the control. Spleen lymphocytes were extracted and the changes of spleen lymphocytes were detected. Compared with transgenic negative mice, the proportion of effector T cells of spleen T cells in the immune system of transgenic mice with anti-PD-1 antibody expressed in breast increased, the proportion of Treg cells decreased, and the IFN-γ, IL-17 and IL-2 expressed in CD4+ T cells increased in varying degrees. Moreover, IL-4, IL-10 and TGF-β in CD4+ T cells did not change, nor did some cell surface protein molecules related to T cell stimulate. There was no significant difference in T cell proliferation between transgenic positive and transgenic negative mice. In transgenic positive mice, the expression of phosphorylated proteins in PI3K/Akt/mTOR and RAS/MEK/ERK pathways were partially up-regulated, but the whole pathway was not completely up-regulated. Therefore, it is feasible to use transgenic mice as host to express monoclonal antibodies related to immune system such as anti-PD-1 antibody.

LED red light up-regulates MAPK signal to promote osteogenic/odontogenic differentiation of human dental pulp stem cells in an inflammatory environment / 口腔疾病防治

Objective @#To study the effect of light-emitting diode (LED) red light on the osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) and its mechanism were discussed. @*Methods@#This study has been reviewed and approved by the Ethics Committee. hDPSCs were cultured by tissue block enzyme digestion. The proliferative capacity of hDPSCs was detected by the CCK-8 at days 1, 3, 5 and 7 under stimulation with 0, 1, 5 and 10 μg/mL lipopolysaccharide (LPS), and the LPS stimulatory concentration was screened. The CG group (mineralization induction), LPS+CG group, and LPS+CG+ (2, 4, 6, 8, and 10 J/cm2) LED red light groups were set. On day 7, alkaline phosphatase (ALP) staining and ALP activity were determined. Relative expression levels of the ALP, osterix (OSX), dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) genes were measured by qRT-PCR. On day 21, alizarin red staining and calcium nodule quantitative determination were performed to screen the best light energy. The LPS+CG group and LPS+CG+LED group (optimal energy) were set up, and the secretion and expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISAs on days 1, 3, 5 and 7. The relative expression levels of the extracellular regulated protein kinases 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases 5 (ERK5) proteins and their phosphorylated proteins in the MAPK signaling pathway were detected by Western blots. After the pathway was blocked, the relative expression levels of the ALP, OSX, DMP-1, and DSPP proteins after LED red light irradiation on day 7 were detected by Western blots.@*Results@# CCK-8 assays showed that the proliferation of hDPSCs induced by 10 μg/mL LPS was lower than that of the 0, 1, and 5 μg/mL groups on the 5th and 7th days (P<0.05), and 10 μg/mL was selected as the LPS stimulatory concentration in the follow-up experiment. ALP staining, ALP activity, gene expression levels of ALP, OSX, DMP-1 and DSPP and calcium nodule quantification in the LPS+CG+4 J/cm2 group were higher than those in the other treatment groups (P<0.05). 4 J/cm2 LED red light had the strongest ability to promote osteogenic/odontogenic differentiation and was used as the LED light energy density in subsequent experiments. ELISA showed that the secretion and expression levels of TNF-α and IL-1β in the LPS+CG+LED group were lower than those in the LPS+CG group on the 5th and 7th days (P<0.05). Western blot analysis showed that 4 J/cm2 LED red light promoted the expression levels of the p-ERK1/2, p-p38, p-JNK and p-ERK5 proteins. After the MAPK pathway was blocked, the expression levels of the ALP, OSX, DMP-1, and DSPP proteins in the LPS+CG+LED+U0126 (ERK1/2 inhibitor), SP600125 (JNK inhibitor), and BIX02189 (ERK5 inhibitor) groups were lower than those in the LPS+CG+LED group (P<0.001). The protein expression levels of ALP, OSX and DMP-1 in the LPS+CG+LED+SB203580 (p38 inhibitor) group were not significantly different from those in the LPS+CG+LED group (P>0.05).@*Conclusion@#In inflammatory conditions, LED red light promotes osteogenic/odontogenic differentiation of hDPSCs. This effect may be attributed to enhancement of the ERK1/2, JNK, and ERK5 signaling pathways, which reduces the production of the inflammatory cytokines TNF-α and IL-1β.

JAK-STAT signaling pathway and rosacea / 中华皮肤科杂志

Studies have shown that rosacea is related to inflammatory factors, neurovascular function, micro-ecological environment and other factors. The Janus kinase (JAK) -signal transducer and activator of transcription (STAT) signaling pathway involves a variety of inflammatory cytokines, and plays an important role in cell proliferation, differentiation, apoptosis, angiogenesis and immune regulation. This review summarizes the JAK-STAT signaling pathway and explores its potential role in rosacea.

Progress in the effect of fluorosis on skeletal muscle and its related molecular mechanisms / 中华地方病学杂志

Fluoride has dual health effects. Proper amount of fluoride plays an important role in bone development, prevention of dental caries and nervous system activity. Excessive fluoride causes chronic systemic diseases with dental fluorosis and skeletal fluorosis as the main symptoms. Fluorosis causes morphological and structural changes and function damage in skeletal muscle. Low concentration of fluoride induces muscle canal hypertrophy in skeletal muscle, while high concentration of fluoride leads to skeletal muscle atrophy by causing a series of signal pathway abnormalities. Abnormal changes in phosphatidylinositol-3-hydroxykinase/protein kinase B (PI3K/Akt) signal pathway, oxidative stress, and ubiquitin-proteasome pathway all play important roles in skeletal muscle injury caused by fluorosis. In this paper, the effect of fluoride on skeletal muscle and its related molecular mechanisms are reviewed.

Progress in molecular signal pathway of dental fluorosis / 中华地方病学杂志

Dental fluorosis is a manifestation of chronic oral fluorosis caused by excessive fluoride intake in childhood. At present, the molecular mechanism of dental fluorosis is still unclear. Ameloblasts are the most sensitive cells to fluoride in tooth tissue. Fluoride affects the proliferation and secretion of ameloblasts through the role of key molecules in the molecular signal pathways, leading to the formation of dental fluorosis. This paper reviews the relationship between the molecular signal pathways [mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β)/Smad, Wnt, Foxo1/Runx2], stress pathways (endoplasmic reticulum stress and oxidative stress) and the occurrence of dental fluorosis in recent years, in order to deeply understand the pathogenesis of dental fluorosis at the molecular level, and provide new ideas for the prevention and treatment of dental fluorosis.

Molecular mechanism of benign biliary stricture inhibition by rosiglitazone-activated peroxisome proliferator-activated receptor gamma

SUMMARY OBJECTIVE: The aim of this study was to investigate whether rosiglitazone-activated peroxisome proliferator-activated receptor gamma can inhibit the occurrence of benign biliary stricture and further elucidate the relevant molecular signaling mechanism. METHODS: The primary cultured rat biliary fibroblasts following experiments were performed using within the fifth generation cells, which were separated from the bile ducts of Sprague-Dawley rats. The primary cultured rat biliary fibroblasts were co-cultured with 10 ng/mL transforming growth factor-beta 1 for stimulating collagen formation. Competent cells were transfected with siRNA that specifically target Smad3 or connective tissue growth factor to inhibit the expression of the corresponding proteins. The cells were incubated with 10 μmol/L rosiglitazone to activate peroxisome proliferator-activated receptor gamma. The cells were incubated with 10 μmol/L GW9662 in the pretreatment session to inactivate peroxisome proliferator-activated receptor gamma. ELISA was used to determine the levels of connective tissue growth factor and type I collagen in the cell supernatant. Western blotting was used to detect the levels of intracellular p-Smad3/t-Smad3. RESULTS: Rosiglitazone-activated peroxisome proliferator-activated receptor gamma inhibited the secretion of type I collagen induced by transforming growth factor-beta 1. Peroxisome proliferator-activated receptor gamma inhibitor GW9662 could significantly reverse the rosiglitazone-triggered inhibition of transforming growth factor-beta 1-induced type I collagen secretion by suppressing peroxisome proliferator-activated receptor gamma activation (p<0.01). Furthermore, we also found that the activation of peroxisome proliferator-activated receptor gamma was accompanied by the inhibition of transforming growth factor-beta 1-induced Smad3 phosphorylation (p<0.01), increased connective tissue growth factor expression (p<0.01), and production of type I collagen (p<0.01), all of which effects elicited by rosiglitazone could be reversed by peroxisome proliferator-activated receptor gamma inhibitor GW9662. CONCLUSION: Peroxisome proliferator-activated receptor gamma activated by rosiglitazone inhibits the transforming growth factor-beta1 -induced phosphorylation of Smad3 and the increased connective tissue growth factor expression as well as inhibits the secretion of type I collagen in biliary fibroblasts.

Potential mechanism of NVP-LDE225 combined with radiotherapy for melanoma / 中华放射肿瘤学杂志

Objective:To explore the potential mechanism and feasibility of sonic hedgehog (SHH) signal pathway inhibitor NVP-LDE225 combined with radiotherapy in the treatment of melanoma.Methods:The Gli1 mRNA expression of the melanoma cells (Melan-A and SK-MEL-2) was detected by qPCR. After treatment with NVP-LDE225, GDC-0449 or combined with radiation for 24 hours, the number and activity of Melan-A and SK-MEL-2 were detected by cell counting and CCK-8 kit. The survival and proliferation ratio of Melan-A and SK-MEL-2 were detected by cell cloning. The changes of cell cycle of melanoma Melan-A cells were determined by flow cytometry. The levels of the Bax and Caspase3 of Melan-A apoptosis protein in melanoma cells were detected by Western blot.Results:NVP-LDE225, an inhibitor of Smo, decreased the mRNA expression of Gli1 in the melanoma cells in a dose-dependent manner, inhibited the proliferation ratio of the melanoma cells, induced apoptosis, and arrested melanoma cells in G 0 / G 1 phase. Gamma ray irradiation after NVP-LDE225 treatment further inhibited the SHH signal pathway, arrested the melanoma cells in G 2 / M phase, and further increased the inhibitory effect on melanoma cell proliferation. Conclusions:NVP-LDE225, an inhibitor of Smo, can inhibit SHH signal pathway in melanocytes, suppress cell proliferation, and further increases the effect of inhibiting cell proliferation after combining with irradiation. It can be used as a potential drug in combination with radiotherapy in the treatment of melanoma, which is worthy of further study.

Clinical features and diagnostic progress of activated phosphoinositide 3-kinase δ syndrome / 中国综合临床

Activated phosphoinositide 3-kinase δ syndrome(APDS) is an autosomal dominant inherited primary immunodeficiency disease that is caused by mutations in PIK3CD or PIK3R1 genes leading to overactivation of the PI3Kδ signaling pathway, first reported by Angulo et al in 2013. The clinical manifestations of the disease are recurrent respiratory tract infections, benign lymph node hyperplasia, autoimmune diseases, lymphoma and so on. Although most patients develop the disease in childhood, there are also reports of adult onset and asymptomatic patients. In addition, the immunophenotype of activated phosphoinositide 3-kinase δ syndrome is changeable, usually the IgA levels are reduced, the IgM levels can be normal or elevated, and the IgG levels are variable, so it is easy to be misdiagnosed at first diagnosis. There is no unified diagnostic standard at present, and timely genetic testing is required to confirm the diagnosis.

Research progress on the role of connexin 43 phosphorylation and its signal pathway in the pathogenesis of sepsis / 中华危重病急救医学

Sepsis is the main cause of death in intensive care unit (ICU). Sepsis and septic shock seriously affect the prognosis of patients and increase the mortality and re-morbidity of patients. Early and timely intervention can reduce the mortality and recurrence rate of patients with sepsis. The occurrence of sepsis may be related to the phosphorylation of connexin 43 (Cx43), which needs to be realized through various signal pathways. The related sites of connexin 43 are phosphorylated through different signal pathways to achieve the precise regulation of sepsis, these sites may be related targets for the treatment of sepsis and provide a direction for accurate treatment of sepsis. This paper mainly analyzes the role of Cx43-related signal pathways such as protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the pathogenesis of sepsis.

Differentially expressed genes in chronic periodontitis and the correlation with disease severity / 国际生物医学工程杂志

Objective:To study the differentially expressed genes in chronic periodontitis (CP) and to explore the correlation with disease severity.Methods:Gene expression profile data associated with CP were screened in the Gene Expression Omnibus (GEO) database and analyzed with GEO2R online software to create volcano maps. Kyoto Encyclopedia of Genes and Genomes (KEEG) and Gene Ontology (GO) analyses were performed on the screened CP-associated differentially expressed genes to predict their possible functions and signaling pathways. The protein-protein interaction database (STRING) was used to analyze the interaction relationships between the encoded proteins of the screened CP-related differentially expressed genes. Cytohubba software was used to identify key genes in the signaling pathway. One120 CP patients and 40 healthy controls were selected. The screened CP-related genes were validated by the real-time polymerase chain reaction (q-PCR) method.Results:A total of 1 151 CP differentially expressed genes that met the requirements were screened. These genes were mainly enriched in the GO pathway for positive regulation of granulocyte differentiation, helper T-cell differentiation, leukocyte aggregation, regulation of acute inflammatory response, chemokine-mediated and endoplasmic reticulum unfolded protein response, as well as in the KEGG pathway for NFB pathway, chemokine pathway, cytokine receptor interaction, leukocyte transendothelial migration pathway, B-cell receptor pathway, Toll-like receptor pathway, etc. The protein-protein interaction network was constructed using the screened CP-related differentially expressed genes, which included 78 nodes and 496 links, with a mean aggregation coefficient and mean connectivity of 0.69 and 12.7, respectively. Cytohubba analysis showed that Sell was a key gene in the signaling pathway, and its relative expression levels in the gingival fluids of the three CP groups with different degrees(1.14±0.46, 0.86±0.41, 0.52±0.46) was significantly lower than that of the control group (1.50±0.65) (all P<0.05). The area under the ROC curve (AUC) of subjects diagnosed with CP using Sell expression levels in gingival fluid was 0.79 (95% CI: 0.71 to 0.86). The AUC values were greater than 0.65 at 95% CI when Sell was used as a biological marker to evaluate the severity of CP. Conclusions:CP-related differentially expressed genes are mainly enriched in the number of pathways associated with the inflammatory response of periodontitis. The expression levels of Sell genes were significantly reduced in the gingival sulcus fluid of CP patients and correlated with the severity of the disease. The Sell genes are expected to be a biomarker for CP grading.

The role of Notch signaling pathway in immune regulation of sepsis / 国际儿科学杂志

Sepsis is a clinical syndrome manifested by organ dysfunction due to disordered inflammatory response after severe infection.The occurrence, development and prognosis of sepsis are closely related to the immune regulation of the body.The essence of sepsis is that the state of excessive proinflammatory response in the early stage gradually progresses to the state of immunosuppression in the late stage, which leads to the body′s inability to resist inflammation and endangers life.As a highly conserved signaling pathway, Notch pathway has the ability to regulate cell growth and differentiation, and participates in the occurrence and development of various inflammatory diseases.In recent years, the important role of Notch signaling pathway in the occurrence and development of sepsis has attracted extensive attention.This article mainly reviews the role of Notch signaling pathway in immune regulation of sepsis.

Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis / 中草药·英文版

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Research progress on the regulation of craniofacial development and malformation by fibroblast growth factor 8 / 口腔疾病防治

@#Fibroblast growth factor 8 (FGF8) is a kind of secretory polypeptide that has crucial roles in the development of various tissues and organs. Current studies have found that FGF8 can regulate the differentiation of cranial neural crest cells by activating the mitogen-activated protein kinase (MAPK) signaling pathway and affect the establishment of mandibular arch polarity and the development of craniofacial symmetry by regulating the expression of target genes. Cleft lip with or without cleft palate, ciliopathies, macrostomia and agnathia are four developmental malformations involving the craniofacial region that seriously affect the quality of life of patients. The abnormal FGF8 signal caused by gene mutation, abnormal protein conformation or expression is closely related to the occurrence of craniofacial malformations, but the molecular mechanism and signaling pathway underlying these malformations have not been fully elucidated. Craniofacial development is a complex process mediated by a variety of signaling molecules. In the future, the role of various signaling molecules in craniofacial development and malformations need to be explored to provide a new perspective and vision for the prevention and treatment of these craniofacial malformations.

Research progress of androgen receptor signaling pathway in castration-resistant prostate cancer / 国际生物医学工程杂志

Prostate cancer is the most common male malignant tumor in the world, and its death toll is second only to lung cancer. Androgen deprivation therapy (ADT) is a major treatment for prostate cancer besides radical surgery. ADT treatment will lead to the inevitable progression of prostate cancer patients to castration-resistant prostate cancer (CRPC). The current research results have confirmed that the transformation from androgen deprivation prostate cancer (ADPC) to CRP is related to the reactivation of the androgen receptor signal pathway. In this review, the research progress on the mechanism of the androgen receptor signaling pathway in CRPC was reviewed in order to provide a scientific basis and new ideas for the diagnosis and treatment of CRP.