Signaling Pathways Related to Renal Interstitial Fibrosis in Diabetic Kidney Disease Regulated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.

Mechanism of Traditional Chinese Medicine in Treatment of Neurodegenerative Diseases by Regulating Polarization Balance of Microglia： A Review / 中国实验方剂学杂志

Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

Transcriptional differential analysis of ocular surface ectoderm and surface ectoderm / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.@*METHODS@#MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.@*RESULTS@#HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.@*CONCLUSION@#Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.

The Latest Research Progress of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients --Review / 中国实验血液学杂志

Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Bone marrow mesenchymal stem cells (MSC) play an important role in the progression of MM. Compared with normal donor derived MSC (ND-MSC), MM patients derived MSC (MM-MSC) exhibit abnormalities in genes, signaling pathways, protein expression levels and cytokines secreted by themselves. Moreover, the exosomes of MM-MSC can interact with the bone marrow microenvironment. The above reasons can lead to MM cell proliferation, chemoresistance, impaired osteogenic differentiation of MM-MSC, and affect the immunomodulatory capacity of MM patients. In order to further understand the pathogenesis and related influencing factors of MM, this paper reviews the latest research progress of MM-MSC.

Signaling Pathways Related to Diabetic Peripheral Neuropathy Treated by Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is one of the common complications of diabetes. The disease has a long course with nerve pain and other symptoms， seriously affecting the quality of life of patients. DPN is related to high glucose in vivo， inflammation， oxidative stress， apoptosis， and autophagy， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， and other signaling pathways. At present， the treatment of DPN mainly focuses on symptomatic treatments such as blood glucose control and neurotrophic therapy， but the effect is not ideal. Therefore， it is particularly important to select a reasonable and effective drug to prevent and treat DPN. In recent years， Chinese medicine has played an important role in the treatment of DPN. Many studies have explored the mechanism of Chinese medicine in the treatment of DPN， and it has been found that some Chinese medicine monomers and compounds can regulate signaling pathways to prevent and treat DPN. This paper reviewed the research results of signaling pathways involved in DPN and the regulation of related pathways by Chinese medicine， aiming to provide references for the clinical treatment of DPN.

Signaling Pathways Related to Irritable Bowel Syndrome Treated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Irritable bowel syndrome （IBS） is a functional gastrointestinal disease， but it often causes extreme gastrointestinal discomfort and prolonged illness， which seriously affects the quality of life of patients. The global incidence rate is increasing year by year. Clinically， western medicine mainly uses oral antispasmodics， secretagogues， and antidepressants， but there are many disadvantages such as adverse reactions and poor long-term efficacy. Therefore， finding an efficient and safe treatment method is an urgent problem to be solved. A large number of studies have shown that traditional Chinese medicine has definite curative and long-lasting effects on the treatment of IBS， which has become a hot research direction in recent years. By searching Chinese and foreign literature， it is found that electroacupuncture， moxibustion， Chinese medicine monomers， and compound decoctions are the main methods in the mechanism research of traditional Chinese medicine in the treatment of IBS-related pathways， and their signaling pathways involve nuclear transcription factor kappa B （NF-κB）， transient receptor potential vanillin subfamily 1 （TRPV1）， 5-hydroxytryptamine （5-HT）， mitogen-activated protein kinase （MAPK）， and so on. Traditional Chinese medicine can repair intestinal inflammation， reduce visceral sensitivity， enhance intestinal mucosal barrier， and regulate intestinal motility by regulating this series of signaling pathways， thereby playing an important role in the treatment of IBS with multi-level， multi-link and multi-target characteristics. Based on the cell signaling pathways， this paper reviewed the research progress on the mechanism of traditional Chinese medicine in the treatment of IBS， hoping to provide theoretical support and diagnosis and treatment ideas for the clinical treatment of IBS with traditional Chinese medicine.

Research progress on targeted drugs for vascular malformations / 口腔疾病防治

@#Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways. Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MAPKK)/extracellular-signal regulated protein kinase (ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the mTOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.

Mechanism of Eucommiae Cortex and Its Active Components in Treatment of Knee Osteoarthritis： A Review / 中国实验方剂学杂志

Knee osteoarthritis （KOA） is a common degenerative joint disease in the middle-aged and elderly. The incidence of KOA is rising as the population aging aggravates and the obese population grows. KOA seriously affects the health and daily life of the patients. The commonly used drugs for the symptomatic treatment of KOA include non-steroidal anti-inflammatory drugs， cartilage protective drugs， and opioid analgesics， which have limited therapeutic effects and induce obvious adverse drug reactions. Eucommiae Cortex is one of the commonly used Chinese herbal medicines for the treatment of KOA， while its pharmacological material basis and mechanism remain unclear， which limits its clinical application. The active ingredients of Eucommiae Cortex for treating KOA mainly include iridoids （geniposide， aucubin）， lignans （pinoresinol diglucoside）， flavonoids （quercetin， astragaloside， baicalein， hyperoside， and kaempferol）， phenylpropanoids （chlorogenic acid）， and polysaccharides. These compounds regulate the levels of inflammatory cytokines， inhibit oxidative stress， protect chondrocytes， balance the synthesis and degradation of extracellular matrix， and control the progression of KOA via the mitogen-activated protein kinase， nuclear factor-κB， phosphatidylinositol-3-kinase/protein kinase B， and Janus kinase 1/signal transducer and activator of transcription 3 signaling pathways. This paper introduces the mechanisms of Eucommiae Cortex and its active components in the treatment of KOA， aiming to provide a theoretical basis for the development of new drugs for KOA.

Chinese Medicine Regulates Signaling Pathways Related to Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells： A Review / 中国实验方剂学杂志

Bone marrow mesenchymal stem cells （BMSCs） are derived from stem cells isolated from bone marrow and have the potential for multidirectional differentiation and self-renewal. Under certain conditions， BMSCs can be induced to differentiate into osteoblast （OB）， chondrocyte， adipocyte， fibroblast， etc. BMSCs play an important role in maintaining the stability of bone structure and balancing bone metabolism. Promoting the proliferation of BMSCs and inducing their differentiation into OB of great significance for the clinical prevention and treatment of osteoporosis， bone defects， fracture healing， and other diseases. Because the proliferation and osteogenic differentiation of BMSCs are complex processes controlled by multiple genes and regulated by multiple signal transduction pathways， traditional Chinese medicine （TCM） happens to have the advantages of multi-bioactive component， multi-target， and multi-pathway synergism， which can affect the proliferation and differentiation of BMSCs through multiple channels and induce the proliferation of BMSCs. The transcription and expression of genes related to osteogenesis can be enhanced to promote the differentiation of BMSCs into OB， so as to achieve the purpose of preventing and treating osteoporosis， bone defects， and other bone diseases. Based on the literature on the intervention of TCM monomers and compounds in the proliferation and osteogenic differentiation of BMSCs， this study reviewed TCM monomers and compounds in promoting the proliferation and osteogenic differentiation of BMSCs by regulating secreted glycoprotein （Wnt）， neurogenic locus notch homolog protein （Notch）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol-3 kinase （PI3K） /protein kinase B （Akt）， bone morphogenetic protein （BMP）/Smad， Janus kinase （JAK）/signal transducer and activator of transcription protein （STAT）， osteoprotegerin （OPG）/receptor activator of nuclear factor-kappa B （RANK）/RANK ligand （RANKL）， and other signaling pathways to provide new ideas for the research and clinical application of Chinese medicine in the prevention and treatment of orthopedic diseases.

Relationship Between Signaling Pathway and Diabetic Retinopathy and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic retinopathy （DR） is one of the most common chronic microvascular complications of diabetes mellitus. It has a high rate of blindness， and the age of onset is gradually getting younger， which seriously affects the physical and mental health and quality of life of patients. The disease is retinal damage induced by diabetes mellitus， which is a kind of fundus disease with the main manifestations of fundus hemorrhage， hard exudation， microhemangioma， cotton-wool spots， neovascularization， etc. In traditional Chinese medicine （TCM）， it is classified into the category of "diabetic cataracts" and other diseases. At present， there is no effective method to prevent the progress of the disease in modern medicine， so it is particularly important to choose a reasonable and effective intervention to prevent and treat DR. Studies have confirmed that TCM has unique advantages in the treatment of DR. It can use its advantages of multiple bioactive components， multiple targets， and multiple pathways to intervene in the development process of DR from various aspects. By searching for the relevant literature on the progress of the intervention of DR with TCM monomers and compounds， this paper mainly reviews the relevant research results of the treatment of DR with multiple signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa-B（NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor erythroid 2-related factor （Nrf2）/hemeoxygenase-1 （HO-1）， Hippo， advanced glycation end products （AGEs）/receptor for advanced glycation end products （RAGE）， and Akt/glycogen synthase kinase-3β （GSK-3β）， so as to provide more ideas and directions for the clinical prevention and treatment of DR.

Research progress of Chinese materia medica in inhibiting malignant biological behavior of lung cancer stem cells / 国际中医中药杂志

Chinese materia medica can inhibit the proliferation, invasion, migration and expression of drug-resistant proteins of lung cancer stem cells (LCSCs), and induce apoptosis and delay self-renewal, as well as exert anti-tumor effects by interfering with their ecological niche, immune microenvironment and aerobic glycolysis, etc. The biomarkers involved mainly include CD133, CD44, ALDH and ABCG2, while the related signaling pathways are Wnt/β-catenin, Hedgehog, and Notch. The research on the intervention of LCSCs by Traditional Chinese Medicine (TCM) is generally few, mostly concentrated in basic research, and the selected experimental indicators have a high repetition rate, involving fewer cell types and signaling pathways; there is a relative lack of clinical trials, which lack an organic connection with basic experiments. In the future, the quality of research is expected to be improved, and in-depth study of TCM with anti-lung cancer stem cell effect should be carried out, with the purpose to promote the precise treatment of lung cancer.

Research Progress of the Effect of Microgravity on Cellular Senescence / 医用生物力学

Microgravity is a typical feature of the space. A large number of space flights and foundation simulation experiments have shown that cells show typical biological characteristics of aging, such as reduced cell proliferation and cell cycle arrest under microgravity or simulated microgravity. However, the molecular mechanism by which microgravity or simulated microgravity affects cellular senescence is not well understood. Understanding the mechanism controlling cellular senescence induced by microgravity environment is helpful for exploring anti-aging strategies and targeted interventions in space. In recent years, domestic and foreign scholars have carried out a number of researches and explorations on the effect of microgravity and simulated microgravity on cellular senescence as well as the related mechanisms. In this review, the latest research progress of this filed was summarized.

Volatile Oil of Linderae Radix Induces Apoptosis and Autophagy of Gastric Cancer AGS Cells via AMPK/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of the volatile oil of Linderae Radix on the apoptosis and autophagy of human gastric cancer cell line AGS， and to explore the regulatory role of adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway in this process. MethodThe volatile oil of Linderae Radix was extracted by steam distillation， and the effect of the volatile oil on the viability of AGS cells was detected by thiazolyl tetrazolium （MTT） colorimetry. The optimal intervention dose and time were determined according to the half maximal inhibitory concentration （IC50） for subsequent research. The blank， low， medium， and high-dose volatile oil （0， 15， 30， 60 mg·L-1） groups and the positive drug cyclophosphamide （CTX， 350 mg·L-1） group were designed. AGS cells were treated with different doses of volatile oil for 48 h. The changes in cell proliferation， cycle， and migration were measured by colony formation assay， flow cytometry， and cell scratch test， respectively. Hematoxylin-eosin （HE） staining was employed to observe the changes of cell morphology， Annexin-V/propidium iodide （PI） double staining to measure the apoptosis， and acridine orange （AO） staining to measure the autophagy level of the cells. Western blotting was employed to determine the expression of the autophagy effectors Beclin-1， p62， microtubule-associated protein 1-light chain 3 （LC3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， cleaved poly ADP-ribose polymerase （PARP）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultCompared with the blank group， 24 h and 48 h of intervention with the volatile oil of Linderae Radix inhibited the viability of AGS cells in a concentration- and time-dependent manner （P<0.05， P<0.01）. Compared with the blank group， the volatile oil decreased the cell proliferation and migration （P<0.05， P<0.01） and blocked the AGS cell cycle in G2/M phase （P<0.05， P<0.01） in a concentration-dependent manner. The cells treated with the volatile oil became spherical and smaller， with the formation of apoptotic bodies and increased apoptosis rate （P<0.05， P<0.01）. As the dose of the volatile oil increased， the number of autophagosomes increased and the red fluorescence gradually enhanced， indicating the elevated level of autophagy. Compared with the blank group， different doses of volatile oil up-regulated the protein levels of Beclin-1， LC3 Ⅱ/LC3 Ⅰ， cleaved Caspase-3， cleaved PARP， Bax/Bcl-2， and AMPK （P<0.05， P<0.01） and down-regulated the protein levels of p62 and p-mTOR （P<0.05， P<0.01）. ConclusionThe volatile oil of Linderae Radix induces the apoptosis and exerts the autophagy-mediated growth inhibition of AGS cells by regulating the AMPK/mTOR signaling pathway.

Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Jianpi Huogu prescription （JPHGP） on the functional injury of vascular endothelial cells caused by alcohol and explore its mechanism based on protein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathway. MethodThrough chick embryo allantoic membrane， thoracic aortic ring， and migration， invasion， adhesion， and lumen formation of human umbilical vein endothelial cells （HUVEC）， the effect of JPHGP with different concentrations （8， 16 and 32 μg·L-1） on angiogenesis was observed in the presence or absence of alcohol. The expression levels of phosphorylation of Akt， JNK， and p38 MAPK were determined by Western blot. ResultAs compared with the normal group， the number and length of capillaries around the arterial ring in the model group were decreased， and the migration， invasion， and lumen formation capacity of HUVEC were decreased （P<0.05， P<0.01）. After treatment with 16 and 32 μg·L-1 JPHGP， the length of neovascularization in chick embryo allantoic membrane was significantly increased （P<0.05， P<0.01）. Compared with the model group， the 8， 16， and 32 μg·L-1 JPHGP groups increased the number of capillaries around the thoracic aortic ring in a concentration-dependent manner （P<0.05， P<0.01）， and the 32 μg·L-1 JPHGP group increased the length of capillaries around the thoracic aortic ring （P<0.05）. The 16 and 32 μg·L-1 JPHGP groups enhanced the migration， invasion， and lumen formation capacity of HUVEC. The results of Western blot showed that， as compared with the normal group， the protein expression levels of p-JNK/JNK， p-p38 MAPK/p38 MAPK， and p-Akt/Akt were significantly decreased in the model group （P<0.01）， and as compared with the model group， the protein expression levels of p-p38 MAPK/p38 MAPK and p-Akt/Akt were significantly increased in the 8， 16， and 32 μg·L-1 JPHGP groups （P<0.01） and the protein expression level of p-JNK/JNK was increased significantly in the 16 and 32 μg·L-1 JPHGP groups （P<0.01）. ConclusionJPHGP has a protective effect on the functional injury of vascular endothelial cells caused by alcohol， and its mechanism may be related to the activation of Akt/JNK/p38 MAPK signaling pathway. Relevant research results will provide certain scientific basis for clarifying the effect of JPHGP on 'invigorating spleen and promoting blood circulation'.

Teriparatide regulates osteoblast differentiation in high-glucose microenvironment through the cAMP/PKA/CREB signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of teriparatide on the differentiation of MC3T3-E1 cells in high-glucose microenvironment and explore the possible mechanism.@*METHODS@#MC3T3-E1 cells cultured in normal glucose or high-glucose (25 mmol/L) medium were treated with 10 nmol/L teriparatide with or without co-treatment with H-89 (a PKA inhibitor). CCK-8 assay was used to detect the changes in cell proliferation, and cAMP content in the cells was determined with ELISA. Alkaline phosphatase (ALP) activity and mineralized nodules in the cells were detected using ALP kit and Alizarin red staining, respectively. The changes in cell morphology were detected by cytoskeleton staining. Real-time PCR was used to detect the mRNA expressions of PKA, CREB, RUNX2 and Osx in the treated cells.@*RESULTS@#The treatments did not result in significant changes in proliferation of MC3T3-E1 cells (P > 0.05). Compared with the cells in routine culture, the cells treated with teriparatide showed significantly increased cAMP levels (P < 0.05) with enhanced ALP activity and increased area of mineralized nodules (P < 0.05). Teriparatide treatment also resulted in more distinct visualization of the cytoskeleton in the cells and obviously up-regulated the mRNA expressions of PKA, CREB, RUNX2 and Osx (P < 0.05). The opposite changes were observed in cells cultured in high glucose. In cells exposed to high glucose, treatment with teriparatide significantly increased cAMP levels (P < 0.05), ALP activity and the area of mineralized nodules (P < 0.05) and enhanced the clarity of the cytoskeleton and mRNA expressions of PKA, CREB, RUNX2 and Osx; the effects of teriparatide was strongly antagonized by co-treatment with H-89 (P < 0.05).@*CONCLUSION@#Teriparatide can promote osteoblast differentiation of MC3T3-E1 cells in high-glucose microenvironment possibly by activating the cAMP/PKA/CREB signaling pathway.

Biological Functions of CD24 in Malignant Tumor and its Application as a Novel Anti-tumor Target / 中国生物化学与分子生物学报

CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.

Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells / 中国临床药理学与治疗学

Platelet-aggregation receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for antithrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.

Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy / 中国临床药理学与治疗学

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.