Mechanism of lncRNA-miRNA-related Signaling Pathways in Gastric Cancer and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Gastric cancer （GC） is one of the most common malignant tumors in the digestive system， with high morbidity and mortality. Early clinical symptoms of GC are not obvious， and most of them have entered the advanced stage after discovery， which greatly reduces the clinical cure rate and affects the quality of life of patients， and the prognosis is very poor. In recent years， with the continuous exploration in the field of bioinformatics， it has been found that micro-RNA （miRNA） and long non-coding RNA （lncRNA） exist as non-coding RNA （ncRNA） without translation ability， and regulate the expression levels of related signal proteins by acting on a certain target， thereby activating or inhibiting a certain signaling pathway， which plays an important role in assisting diagnosis， guiding clinical medication， and judging prognosis in the progress of GC. Chinese medicine is easily accepted by patients because of its good curative effect and less side effects. In the present basic studies， with the interaction mechanism between miRNA， lncRNA and signaling pathways as the breakthrough point， various studies on the regulation of related signaling molecules and signaling pathways by Chinese medicine have been carried out. A large number of experimental data have proved that the development of GC is closely related to the interaction of miRNA， lncRNA， and related signaling pathways， and Chinese medicine， with multi-target， multi-mechanism， and multi-pathway characteristics， affects various signaling molecules and signaling pathways and intervenes in the progress of GC cells. This paper reviewed the basic research on lncRNA， miRNA molecules， and main signaling pathways involved in the occurrence and development of GC， and summarized specific molecular mechanisms of Chinese medicine in the regulation of each signaling pathway， hoping to provide references for modern research of Chinese medicine in the intervention of GC progress at the molecular level.

Myocardial insulin resistance and systemic arterial hypertension / Resistência insulinica miocárdica e hipertensão arterial sistêmica

Background: Low availability of Glut-4 transporters in the sarcolemma of cardiac cells characterizes myocardial insulin resistance (MIR), which is triggered separately from generalized insulin resistance. Insulin receptors are quite evident in the heart muscle and vessels, and mitochondrial activity performs a significant role in MIR preserving cellular homeostasis through cell reproduction, cells livelihoods, and energy generation. Objective: To evaluate the MIR mechanism and its association with hypertension by signaling pathways design. Methods: PubMed database was employed to search for reviews publications with MIR. The referenced data of the signaling pathway was chosen by aggregating references from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A signaling pathway was designed based on MIR research manuscripts, where we show several mechanisms included in the MIR. The KEGG server was employed to exploit the interrelationship protein-protein, and elaborate signaling pathway diagram. The signaling pathway mapping was carried out with PathVisio software. Results: We selected 42 articles from a total of 450 articles in the PubMed database that presented a significant association between the terms "insulin resistance myocardial" AND "signaling pathway" AND "systemic arterial hypertension". Founded on database-validated research papers, we chose well-founded pathways and we succeeded in representative description of these pathways. The reproduction contigs taken from the KEGG database designed the signaling pathway of the bio-molecules that lead to MIR. Thus, the acting among multiple mechanisms releases factors that participate in the development of MIR. Conclusion: The interaction among various mechanisms and molecular interactions are important factors in developing MIR (AU).

Introdução: A baixa disponibilidade de transportadores Glut-4 no sarcolema das células cardíacas caracteriza a resistência à insulina miocárdica (MIR), que é desencadeada separadamente da resistência generalizada à insulina. Os receptores de insulina são bastante evidentes no músculo cardíaco e nos vasos, e a atividade mitocondrial desempenha uma função significativa no MIR, preservando a homeostase celular pela reprodução celular, subsistência das células e geração de energia. Objetivo: Avaliar o mecanismo MIR e sua associação com hipertensão por meio do desenho de vias de sinalização. Métodos: A base de dados PubMed foi empregada para pesquisar publicações de revisões com MIR. Os dados referenciados da via de sinalização foram escolhidos agregando referências do banco de dados Kyoto Encyclopedia of Genes and Genomes (KEGG). Uma via de sinalização foi projetada com base em manuscritos de pesquisa MIR, onde mostramos vários mecanismos incluídos no MIR. O servidor KEGG foi empregado para explorar a inter-relação proteína-proteína e elaborar o diagrama de vias de sinalização. O mapeamento das vias de sinalização foi realizado com o software PathVisio. Resultados: Foram selecionados 42 artigos de um total de 450 artigos na base de dados PubMed que apresentavam associação significativa entre os termos "insulin resistance miocárdio" AND "signalingway" AND "systemic arterial hypertension". Com base em trabalhos de pesquisa validados por banco de dados, escolhemos caminhos bem fundamentados e conseguimos uma descrição representativa desses caminhos. Os contigs de reprodução retirados do banco de dados KEGG desenharam a via de sinalização das biomoléculas que levam ao MIR. Assim, a atuação entre múltiplos mecanismos libera fatores que participam do desenvolvimento da MIR. Conclusão: A interação entre vários mecanismos e interações moleculares são fatores importantes no desenvolvimento de MIR (AU).

Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides / 中草药·英文版

Seaweed is a traditional Chinese medicine homologous to food, in which polysaccharides are responsible for anti-cancer by enhancing immunity, inducing cancer cell apoptosis, inhibiting cancer cell invasion and metastasis or directly scavenging oxidative free radicals that induce cancer cell changes. Among them, regulating immunity and promoting cancer cell apoptosis are intensively studied due to the important role in preventing cancer. Here we reviewed seaweed in the apoptosis-inducing signaling pathways including PI3K/AKT, ROS and JNK and discussed challenges in studying seaweed.

Progress of Experimental Research on Effect of Traditional Chinese Medicine on Proteins Associated Asthmatic Airway Remodeling / 中国实验方剂学杂志

Airway remodeling is an important pathological basis of asthma， and also the main reason for the difficulty in asthma therapy. By referring to the experimental reports on the treatment of airway remodeling in asthma with traditional Chinese medicine （TCM） in recent years， the authors comprehensively analyzed the effect of TCM on proteins related to airway remodeling in asthma， and it was found that TCM could regulate the signal pathway related proteins （such as transforming growth factor-β1/Smads， extracellular signal-regulated kinase and Wnt/β-catenin）， structural proteins （such as α-smooth muscle actin， collagen， osteopontin and fibrin） and gene regulatory proteins （such as matrix metalloproteinase-9， vascular endothelial growth factor， B lymphoma cell-2 related X protein）， and participate in the regulation of airway remodeling signaling pathway， tissue structure homeostasis and gene expression， so as to inhibit airway remodeling in asthma. In conclusion， TCM can improve the pathological morphology of airway remodeling and delay the progress of airway remodeling by controlling the corresponding proteins. At present， however， a lot of studies are limited to single Chinese herbal or TCM extract in animal experiments， and there is a lack of clinical research. It is suggested to establish a systematic and multi-level study on the mechanism of TCM for treating airway remodeling in asthma based on the theory of TCM， so as to provide a better reference for clinical practice.

The Role and Mechanisms of Mechanical Stimulation in Degeneration of Vertebral Cartilage Endplates / 医用生物力学

The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.

Research progress on mechanism and signal pathway of ocular pruritus / 国际眼科杂志(Guoji Yanke Zazhi)

@#Ocular pruritus is one of the common symptoms of ocular surface diseases. People know little about the mechanism of ocular pruritus. In clinical practice, eye drops can only be used to relieve eye discomfort. Eye itch often makes patients feel extremely painful and uncomfortable. The itch is afferent from primary neurons, mainly small-diameter unmyelinated afferent neuron fibers, whose cell bodies are located in the dorsal root ganglia or trigeminal ganglia. These neurons transmit the itch from the skin to the central nervous system. In the spinal cord, these afferent nerves synapse with secondary neurons in the dorsal horn and send signals to the brain. Pruritus sensory neurons are generally considered to be a subgroup of pain neurons. Intensity coding theory suggests that at low emissivity, neuronal activity can cause the sensation of itching. With the advancement of molecular biology and neuroscience technology, it was discovered that one of the main functions of Mrgpr(mas-related G protein-coupled receptor)protein is pruritus, and most of Mrgprs(all MrgprA, MrgprB and MrgprC subfamily members, and MrgprD)are almost exclusively expressed in specific dorsal root and trigeminal ganglion neurons. This review will introduce the mechanism and signal pathways of ocular pruritus, as well as the role of Mrgpr protein in ocular pruritus, and provide help for the treatment of ocular pruritus.

Biomechanical Effects of Primary Cilia in Articular Cartilage / 医用生物力学

Biomechanical factors play a crucial role in the steady-state maintenance of articular cartilage. The primary cilium (PC) is a kind of organelle which can sense mechanical and chemical signals at the same time. It is also distributed on the surface of chondrocyte membrane. It is involved in multiple signal transduction pathways as well as in the process of chondrocyte phenotype maintenance and material metabolism. Abnormalities in PC are also associated with a variety of human bone and joint diseases. This paper mainly discusses the mechanism of PC in mechanical microenvironment of chondrocytes and the interaction with other signaling pathways, and explores its relationship with bone and joint diseases, so as to provide some scientific basis for clinical and basic research in orthopedics.

Effect of Tongbiantang on PKA/MPKA Signal Pathway in Colon Tissue of STC Rat Model / 中国实验方剂学杂志

Objective: To explore the effect of Tongbiantang on protein kinase A(PKA) and mitogen-activated protein kinase(MAPK) signal pathway in colon tissue of slow transit constipation(STC) rats and its related mechanism. Method: Eighty SD rats were randomly divided into blank group and model group, 20 rats in blank group, 60 rats in model group, half male and half female; blank group was fed with common diet, model group was fed with compound phenylethylpiperidine, after 120 days of modeling, 10 rats in blank group and 20 rats in model group were randomly selected, and 2 rats were determined. Four-hour stool volume, water content and small intestinal charcoal powder propelling rate were observed to observe the number of stool particles retained in colon and evaluate the success of STC rat modeling. After 1 week of drug withdrawal, 40 rats in model group were randomly divided into model group(33 g·kg-1), Tongbiantang group, Tongbiantang+H89 group (PKA signaling pathway blocker,5 mg·kg-1), Tongbiantang+U0126 group (MPKA signaling pathway blocker,0.1 mg·kg-1) each. After 4 weeks of intervention with Tongbiantang, the amount of stool excretion, water content and small intestinal charcoal powder propelling rate were measured in 10 rats, and the number of stool grains in colon was observed. The protein content and mRNA expression in aquaporins 3(AQP3), AQP4, PKA and MAPKs signaling pathways in colon was determined by immunohistochemical staining (IHC), Western blot and Real-time fluorescence quantitative PCR (Real-time PCR). Result: Compared with the blank group, the 24-hour stool volume, fecal water content, small intestinal charcoal propelling rate and the number of fecal particles in colon of rats in the model group were significantly decreased (PPPPPConclusion: Tongbiantang can inhibit the PKA and MPKA signal pathways, thus down-regulate the expression of AQP3 and AQP4, increase intestinal peristalsis and intestinal water, and effectively treat STC.

Role of miRNA-340 in modulating gastric cancer cell proliferation and bioinformatic analysis / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of miRNA-340 for regulating the proliferation of gastric cancer (GC) cells and predict its interacting circular RNAs (circRNAs), its downstream target genes and the involved signaling pathways.@*METHODS@#The differentially expressed miRNAs in GC cell lines were analyzed and screened using miRNA microarrays. The expression level of miRNA-340 in 21 pairs of GC tissues and adjacent normal tissues was detected using real-time PCR. MTT and EdU assays were performed to examine the effect of miRNA-340 on the proliferation ability of HFE145 and BGC-823 cells. We also tested the effect of miRNA-340 inhibition on subcutaneous tumorigenesis of GC cells in a nude mouse model. The downstream target genes of miRNA-340 and the probable signal pathways were predicted online using Targetscan and DAVID database, respectively. The interacting circRNAs of miRNA-340 were analyzed using starBase platform.@*RESULTS@#Among the differentially expressed miRNAs, miRNA-340 was significantly down-regulated in GC cell lines. Real-time PCR results showed that the expression of miRNA-340 was significantly lower in GC tissues than in the adjacent tissues ( < 0.05). MTT and EdU cell proliferation assays showed that miRNA-340 overexpression inhibited the proliferation of GC cells in vitro. In the nude mouse models, the proliferation of GC cells transfected with miRNA-340 inhibitor was obviously enhanced. Bioinformatics analysis suggested that miRNA-340 had 21 target genes with 3 or more conserved sites, and these genes were involved in tumorigenesis and invasion. The top 10 circRNAs were selected as the most powerful sponge circRNAs interacting with miRNA-340.@*CONCLUSIONS@#miRNA-340 may play the role of a tumor suppressor in tumorigenesis and progression. Overexpression of miRNA-340 suppress the proliferation of GC cells, suggesting its involvement in the development of GC along with multiple circRNAs.

Research progress of signaling pathways in liver fibrosis / 中华肝脏病杂志

Hepatic fibrosis is a reversible pathological process in which the liver cells has been subjected to long periods of various acute and chronic injuries leading to the activation of hepatic stellate cells (HSCs), imbalance of extracellular matrix synthesis, degradation, and deposition. Among them, the activation of hepatic stellate cells is the key link for the occurrence of hepatic fibrosis, so intervention of HSCs activation and proliferation is expected to reverse the progression of liver fibrosis. Thus, this paper summarizes the signaling pathways involved in the liver fibrosis progression, with hepatic stellate cells as the center, to provide new ideas for the study of anti-fibrosis.

Anti-inflammatory mechanism of heat-clearing and detoxifying Chinese herbs / 中国中药杂志

Heat-clearing and detoxifying Chinese herbs (HDCHs) are mainly used to treat carbuncle, sore throat, erysipelas, gills, dysentery and other diseases induced by heat-toxicity. Inflammation is a defensive response to damaging factors in living organism with vascular system. In recent years, a large amount of experimental and clinical studies showed that HDCHs had good therapeutic effect on inflammation. This review analyzed the anti-inflammatory mechanism of 11 HDCHs by retrieving literature in past 5 years, including Lonicerae Japonicae Flos (Jinyinhua), Lonicerae Flos (Jinyinhua), Lonicerae Japonicae Caulis (Rendongteng), Forsythiae Fructus (Lianqiao), Rhizoma Coptidis（Huanglian）, Gardeniae Fructus (Zhizi), Andrographis Herba (Chuanxinlian), Taraxaci Herba (Pugongying), Scrophulariae Radix (Xuanshen), Pulsatillae Radix (Baitouweng), and Agrimoniae Herba (Xianhecao). The data showed that the regulatory effect of HDCHs on inflammation may be involved mainly in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) or janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, with similarity of action links among these three. Based upon the analysis of literature, we proposed some promising directions in this research field, providing a reliable theoretical basis for both experimental researches and clinical practices of HDCHs.

Interferon regulatory factor 5 and systemic lupus erythematosus / 国际儿科学杂志

Interferon regulatory factor (IRF)members are composed of 10 different proteins,including IRF1 ～ IRF9 and viruses IRF(V-IRF).These IRFs regulate the transcription of type I IFN genes as transcription factors.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a large number of autoantibodies and precipitated immune complexes,which can cause the damage of multiple organs and systems.Type I interferon system,especially the IFN-α is an important pathogenic factor in the process of SLE morbidity.SLE patients may have high level of IFN-α,which could affect the activation of the immune system to promote the development of SLE through the regulation of a variety of immune cells' activation,differentiation and function.Besides IRF3 and IRFT,the transcription factor IRF5 gene has also been shown to be related to the production of type I interferon and is an important regulator of the IFN pathway,and its genetic polymorphism and expression abnormality lead to the susceptibility of SLE.In addition to regulating the expression of type I IFN genes,IRF5 is also associated with other signaling pathways,including B cell transformation of IgG,macrophage polarization and apoptosis,and these signaling pathways in the pathogenesis of SLE also play a very important role.This article reviews the role of IRF5 in the development of SLE disease.

Research progress in role and mechanism of ferroptosis in hepatocellular carcinoma / 中国药理学通报

Hepatocellular carcinoma ( HCC) is the most com-mon primary liver cancer resulted from various etiological fac-tors, among which HBV infection is the most important reason in China. The development and progression of HCC are regulated by a variety of cytokines and intracellular signaling pathways. In recent years, both clinical and basic studies have shown that fer-roptosis plays an important role in the occurrence of HCC. Fer-roptosis can affect the development of liver diseases by regulating the level of intracellular iron and lipid peroxidation. Many schol-ars believe that ferroptosis can be used as a target for the diagno-sis, prevention and treatment of HCC. In this review, the role of ferroptosis in HCC and its research progress has been summa-rized, including ferroptosis summary, the relationship between ferroptosis and HCC, and the molecular mechanisms of ferropto-sis in HCC.

Progress of pancreatitis-cancer transformation / 肿瘤研究与临床

Pancreatitis is one of the important risk factors in the occurrence of pancreatic neoplasms. Several inflammation-related transcription factors and pathways have been confirmed to be involved in the carcinogenesis, but molecular mechanisms of pancreatitis-cancer transformation are still unclear, which largely limits the further development of potential anti-tumor drugs. Thus, it is important to figure out the underlying molecular mechanisms of pancreatitis-cancer transformation. This paper reviews the main biological characteristics, relevant important signaling pathways, clinical intervention strategies of pancreatitis-cancer transformation.

Treadmill exercise can significantly improve bone metabolism in osteoporosis / 中华物理医学与康复杂志

Objective To study the effect of treadmill exercise on the bone metabolism of osteoporotic rats and the regulatory role of Wnt/β-catenin signaling in it. Methods Thirty-two female Sprague-Dawley rats aged 2 months were randomly divided into a sham-operated quiet group ( S group ) , an ovariectomized quiet group ( O group) , a sham-operated exercise group ( ST group) and an ovariectomized exercise group ( OT group) with 8 rats in each group. The ovariectomies established a model of post-menopausal osteoporosis. The ovaries of groups O and OT were removed, while those of the S and ST groups were exposed, but not removed. All of the rats were free to move in their cages, but those in the ST and OT groups also underwent treadmill training every day for 10 weeks. All of the rats were sacrificed 24 hours after the last exercise session. Bone mineral density ( BMD) of the femur was measured using dual energy X-ray absorptiometry, while serum calcium, phosphorus and alkaline phosphatase were detected with a biochemical analyzer. Serum osteocalcin was quantified by radioimmunoassay. A three point bending test quan-tified the biomechanical properties of the femors. The expression of Wnt/β-catenin was measured through western blotting. Results After the intervention the average BMD of group O was significantly lower than that of group S, that of group ST was significantly higher than group S and that of group OT significantly higher than group O ( P≤0.05) . The relative expression of Wnt/β-catenin protein P-GSK-3βin group ST was significantly lower than in group S ( P≤0.05) . The relative expressions ofβ-catenin and cyclin D1 in group ST were significantly higher than in group S ( P≤0.05) . The relative expression of protein P-GSK-3βin group OT was significantly lower than in group O, while that of β-catenin and cyclin D1 was significantly higher (P≤0.05). Conclusion Treadmill exercise can signifi-cantly improve bone metabolism in osteoporotic rats. The mechanism may be related to activating the Wnt/β-catenin signaling pathway.

Applications of proteomics in the study of cell signal pathways / 中国药科大学学报

Various signal transduction pathways in cells are closely related to the biological processes,while the proteins play an important role in the process of signal transductions.Proteomics,which is one of the effective methods for the study of cell signal pathways,can conduct proteomic analysis systematically as well as explore the expression of functional proteins related to the physiological characteristics in organism and in the initiation and progression of diseases.Nowadays,proteomics has been successfully applied in the studies of many kinds of signal pathways.In this paper,proteomic study in signal pathways related to liver disease,tumors,pathogenic mechanism of pathogens and metabolism are reviewed,in order to provide a reference for future research and applications of proteomics in the related fields.

Research progress in vasculogenic mimicry in multiple tumors / 中南大学学报(医学版)

Vasculogenic mimicry (VM) is a brand-new tumor vascular pattern with the ability to form vessellike networks without participation of endothelial cells and independent on angiogenesis.It can provide adequate blood supply for tumor growth.The formation of VM involves multiple molecule mechanisms and signal pathways,including cancer stem cell and epithelial-mesenchymal transition.As a unique blood-supply pattern,VM is associated with cancer invasion,metastasis and poor prognosis.Because of its important role in cancer progression,VM will become a new target for therapy of cancers.

New focus on osteoporosis: Differentiation fate of bone marrow-derived mesenchymal stem cells / 第二军医大学学报

Osteoporosis is a frequently seen metabolic bone disease characterized by reduced hone mass, reduced bone mineral density and hone micro-structure destruction. Patients with osteoporosis are prone to brittle fractures, and the incidence of osteoporosis is increased annually. The pathogenesis of osteoporosis is related to the imbalance between osteoblasts and osteoclasts. On one hand, the activity of osteoclasts is increased, with high bone resorption; on the other hand, the function of osteoblasts is attenuated, with low osteogenesis; and finally the two reasons lead to loss of net bone mass. Osteogenesis is closely related to the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In osteoporotic patients, the adipogenic differentiation of BMSCs is increased and the osteogenic differentiation is decreased. The differentiation fate of BMSCs is regulated by BMP/Smad, Wnt, Notch, Hedgehogs and other signal pathways, involving microRNAs. transcription factors, epigenetic and other regulatory mechanisms, which is a focus in current research. the future studies need to focus on finding the key factors in determining the differentiation fate of BMSCs and BMSCs transplantation, so as to cast new lights on the treatment of osteoporosis.

Effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms / 中华烧伤杂志

Objective@#To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms.@*Methods@#Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-β1 (TGF-β1), and endostatin+ TGF-β1 groups according to the random number table, with 3 wells in each group. Cells in blank control group were cultured with DMEM medium for 24 h. Cells in endostatin group were cultured with DMEM medium containing 5 μg/mL endostatin for 24 h. Cells in PDGF-BB group and TGF-β1 group were cultured with DMEM medium containing 200 ng/mL PDGF-BB and 10 ng/mL TGF-β1 for 24 h, respectively. Cells in endostatin+ PDGF-BB group were pretreated with DMEM medium containing 5 μg/mL endostatin for 48 h and then cultured with DMEM medium containing 200 ng/mL PDGF-BB for 24 h. Cells in endostatin+ TGF-β1 group were pretreated with DMEM medium containing 5 μg/mL endostatin for 48 h and then cultured with DMEM medium containing 10 ng/mL TGF-β1 for 24 h. The content of type Ⅰ collagen in the cell culture supernatant of three wells in each group was determined by enzyme-linked immunosorbent assay. The protein expression levels of α-smooth muscle actin (α-SMA), PDGF receptor β (PDGFRβ), phosphorylated PDGFRβ (p-PDGFRβ), and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) of three wells in each group were detected by Western blotting. Data were processed with one-way analysis of variance and SNK test.@*Results@#(1) Compared with (5.05±0.29) pg/mL in blank control group, content of type Ⅰ collagen in the cell culture supernatant of endostatin group [(4.72±0.37) pg/mL] was close to it (P>0.05), content of type Ⅰ collagen in the cell culture supernatant of PDGF-BB group and TGF-β1 group [(8.60±0.57) and (9.20±0.64) pg/mL, respectively] was higher (with P values below 0.05). Content of type Ⅰ collagen in the cell culture supernatant of endostatin+ PDGF-BB group [(5.32±0.17) pg/mL] was lower than that of PDGF-BB group (P<0.05), and content of type Ⅰ collagen in the cell culture supernatant of endostatin+ TGF-β1 group [(5.41±0.20) pg/mL] was lower than that of TGF-β1 group (P<0.05). (2) Compared with those in blank control group, protein expression levels of α-SMA, PDGFRβ, p-PDGFRβ, and p-ERK1/2 of cells in endostatin group showed no obvious differences (with P values above 0.05), while those in PDGF-BB and TGF-β1 group were significantly higher (with P values below 0.01). Protein expression levels of α-SMA, PDGFRβ, p-PDGFRβ, and p-ERK1/2 of cells in endostatin+ PDGF-BB group and endostatin+ TGF-β1 group were significantly lower than those in PDGF-BB group and TGF-β1 group, respectively (with P values below 0.05).@*Conclusions@#Pretreatment of endostatin can inhibit the fibrosis of human skin fibroblast and its transformation into myofibroblast, which may be related to the down-regulation of protein expression of p-PDGFRβ, PDGFRβ, and p-ERK.

Directional differentiation of mouse mesenchymal stem cells into neuronal cells induced by salidroside via Notch and BMP signal pathway / 中草药

Objective: To study the molecule mechanism of salidroside inducing mesenchymal stem cells (MSCs) to directionally differentiate into neuronal cells via bone morphogenetic protein (BMP) and Notch signal pathways. Methods: Experiments were divided into control, induced, and blocked groups. The technologies, such as immunofluorescence, real-time PCR, and Western blotting were used to analyze the effect of salidroside on cellular proliferation, morphosis, and BMP and Notch signal pathways. Results: The immunofluorescence results showed that salidroside could affect cellular proliferation and induce MSCs to form the morphosis of neuronal cells. The positive rate of Notch1 and Jadge1 was significantly decrease to compare with the control (P < 0.05), real-time PCR results indicated that mRNA expression of Notch1 and Hes1 was obviously down-upregulated when treated with salidroside for 12-72 h (P < 0.05). However, Notch signal pathway was blocked with DAPT, a special inhibitor of Notch, the marker molecules of neuronal cells expression, such as neuron-specific enolase (NSE), microtubule associated protein 2 (MAP2), and β-tubulin III, were significantly increased when cells were treated with salisroside (P < 0.05). The mRNA levels of Smad5 and Smad8 were up-regulated when cells were treated with salidroside for 12 h, expression of Smad1/5/8 protein was increased at 12 and 24 h. When BMP signal pathway was blocked with Noggin, a special inhibitor of BMP, NSE, MAP2, and β-tubulin III mRNA expression was decreased to compare with the salidroside induced group (P < 0.05); When Notch and BMP signal pathways were simultaneously blocked with DAPT and Noggin, MAP2 and β-tubulin III mRNA expression was increased more obviously than that of the blocked with Noggin. Meanwhile the expression of NSE and β-tubulin III protein was also up-regulated (P < 0.05). Conclusion: Salidroside promotes neuron-like differentiation of MSCs by negatively regulating the Notch pathway and activating BMP signal pathway, it plays a vital role for salidroside to inhibit Notch pathway on affecting MSCs differentiation.