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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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NF-kappa B , Alzheimer Disease , Network Pharmacology , Anthocyanins , Berberis , Lipopolysaccharides , Molecular Docking Simulation , Myeloid Differentiation Factor 88 , Neuroinflammatory Diseases , Toll-Like Receptor 4 , I-kappa B ProteinsABSTRACT
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.
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Mice , Animals , Female , Mice, Transgenic , Spleen/metabolism , CD4-Positive T-Lymphocytes/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cytokines/metabolismABSTRACT
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.
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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.
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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.
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3-iodothyronamine（T1AM）is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ，slowing heart rate ，promoting lipolysis ， reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine，but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger ， T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM，in order to provide new therapeutic drugs of cardiovascular ，metabolic diseases and nervous system diseases.
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@#Objective - - （BCL2L2）- （ ） To investigate the differential expression of the fusion gene BCL 2 like protein 2 poly A （PABPN1） （ ） binding protein nuclear 1 induced by sodium arsenite SA and its methylated metabolites in 16HBE cells and the Methods ） ， related mechanism. i The 16HBE cells exposed to SA at concentrations of 1.5 3.0 and 4.5 µmol/L were set as -， - - low medium and high dose arsenic exposure groups. The 16HBE cells exposed to 4.5 µmol/L monomethylarsonic acid （ ）， （ ） ， MMA dimethylarsonic acid DMA and SA were set as MMA group DMA group and SA group. The 16HBE cells without ， BCL2L2-PABPN1 toxic stimulation were set as control group. After the cells were cultured for 48 hours the expression of was - （ - ） ） （ ） detected by quantitative real time polymerase chain reaction qRT PCR . ii Two small interfering RNA siRNA silencing 基金项目：国家自然科学基金（ ）； 年云南省科技厅昆明医科大学应用基础研究联合专项面上项目 82160607 2021 （ ） 202101AY070001-054 作者简介：施雅（ —），女，在读大学本科生，主要从事劳动卫生与环境卫生学研究；尹锦瑶（ —），女，在读劳动卫生与环境卫 2001 1995 生学硕士研究生，主要从事劳动卫生与环境卫生学研究；施雅和尹锦瑶为共同第一作者 通讯作者：何越峰教授，博士研究生导师，- ： E mail heyuefeng@kmmu.edu.cn中国职业医学 年 月第 卷第 期 ， ， ， · · 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 523 BCL2L2-PABPN1， - fragments were designed and transfected into 16HBE cells to knockdown which were set as siRNA 1 group - - BCL2L2-PABPN1 and siRNA 2 group. Non transfected control group without knockdown of transfection was set up. After ， BCL2L2-PABPN1 - culturing for 48 hours the expression level of in the three groups of cells was detected by qRT PCR. The cell - survival rate and early apoptosis rate were detected by MTS method and JC 1 mitochondrial membrane potential detection ， （ ） ， method respectively. The apoptosis was detected by Hoechest33342/propidium iodide PI double staining and the expression - Results ） level of P53 signaling pathway related proteins was detected by Western blotting. i The relative expression of BCL2L2-PABPN1 （P ） BCL2L2- in 16HBE cells increased with the increasing SA doses <0.01 . The relative expression of PABPN1 - ， - - in high dose arsenic exposure was higher than that in control group low dose and medium dose arsenic exposure （ P ） BCL2L2-PABPN1 ， groups all <0.05 . The relative expression of in SA group was higher than those in control group MMA （ P ） BCL2L2-PABPN1 group and DMA group all <0.05 . The relative expression of showed no significant difference between ， （ P ） ） BCL2L2-PABPN1 control group MMA group and DMA group all >0.05 . ii The relative expression levels of and cell - - - （ P ） survival rate in siRNA 1 group and siRNA 2 group were lower than those in non transfected control group all <0.05 . ， （P ） However there was no significant difference in the early apoptosis rate among the three groups >0.05 . The results of - Hoechest33342/PI double staining showed that the number of nuclear shrinkage and early apoptotic cells in siRNA 1 group and - - ， - siRNA 2 group was higher than that in non transfected control group. The relative protein expression levels of P53 phospho ， - - ， - - （ P ） p53 BCL 2 associated death promoter P21 and cytochrome C in siRNA 1 group and siRNA 2 group were higher all <0.05 , - - P and the relative protein expression levels of P53 up regulated modulator of apoptosis were lower (all <0.05), when compared - Conclusion with the non transfected control group. SA may block the apoptosis of 16HBE cells by inducing the expression of BCL2L2-PABPN1 fusion gene . The mechanism may be related to the activation of P53 signaling pathway. The SA methylated BCL2L2-PABPN1 BCL2L2-PABPN1 - metabolites MMD and DMA had no effect on the expression of . may affect anti apoptosis BCL2L2 PABPN1 through affecting the synergistic effect of and genes.
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Cerebral ischemia/reperfusion (I/R) injury refers to an aggravated brain tissue damage caused by the restoration of blood supply after acute ischemia for a period of time. Its pathogenesis is complex, including oxidative stress, inflammatory response, and excitatory amino acid toxicity. The effective clinical treatments of cerebral I/R injury after ischemic stroke (IS) are limited. Nuclear factor E 2-related factor 2 (Nrf2), the most critical antioxidant transcription factor in cells, can coordinate multiple cytoprotective factors to inhibit oxidative stress. Since Nrf2 signaling pathway is considered to be one of the most important cellular defense mechanisms against oxidative stress, targeting Nrf2 intervention has become an attractive therapeutic strategy in the prevention and treatment of cerebral I/R injury. This review focuses on the structure, regulation and function of Nrf2 signaling pathway, as well as its activation and potential therapeutic targets in cerebral I/R injury. The important role and future potential of Nrf2 pathway in the pathogenesis of cerebral I/R injury were discussed.
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Objective:To determine the protective effect of fasudil on acute lung injury in septic mice.Methods:Forty-five 4-6-week-old male C57BL mice were randomly(random number) assigned to three groups ( n=15 each group): control group, lipopolysaccharide (LPS) group and Fasudil intervention group (FAS+LPS). Acute lung injury model of septic mice was established with an intraperitoneal injection and intratracheal infusion of LPS. The mice in the FAS+LPS group were injected with fasudil hydrochloride intraperitoneally 30 min before intraperitoneal LPS injection and 1 h after intratracheal LPS infusion, respectively. All mice were sacrificed at 4 h after modeling, and lung tissues were collected. Hematoxylin-eosin staining was preformed to observe the morphological changes in the lung tissue. The wet /dry weight (W/D) ratio, malondialdehyde (MDA) content and the activity of myeloperoxidase (MPO) in the lung tissues were detected. Caspase-3 expression was examined by immunohistochemical (IHC) staining. Western blot was employed to detect the expression of RhoA, ROCK1, endothelial nitric oxide synthase (eNOS), and p-eNOS. Results:Inflammatory cell infiltration and erythrocyte exudation were significantly reduced, and the degree of interstitial oedema and derangement of alveolar structure appeared in a decreasing degree after FAS intervention. Compared with the LPS group, the W/D ratio, MDA content, MPO activity and the expression of Caspase-3 in the FAS+LPS group were significantly reduced (all P<0.01). Meanwhile, the expression of RhoA and ROCK1 of the LPS group were obviously higher than those in the control group ( P<0.05), and p-eNOS was obviously lower than that in the control group ( P<0.05). Furthermore, the expression of RhoA and ROCK1 of the FAS+LPS group were obviously lower than those in the LPS group, and p-eNOS was obviously higher than that in the LPS group. There was no significant difference on the expression of eNOS among the three groups. Conclusions:Fasudil can alleviate the degree of inflammatory cell infiltration, reduce apoptosis in lung tissue, inhibit the RhoA/ROCK1 signaling activity, and promote the phosphorylation expression of eNOS in septic mice.
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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.
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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.
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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.
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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.