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Diabetic nephropathy(DN)is one of the most important complications of diabetes.Its pathogenesis is com-plex and has not been fully elucidated.Epithelial-mesenchymal transition(EMT)plays an important role in the development of DN.Relevant data show that glycogen synthesis kinase-3β(GSK-3β)participates in the process of EMT through multiple sig-naling pathways and affects the occurrence and progression of DN.This article reviews the research progress of GSK-3β in-volved in EMT in DN.
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AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.
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Chronic obstructive pulmonary disease （COPD） is a heterogeneous disease characterized by incompletely reversible airflow limitation that progresses over time. Its recurrent and incurable nature imposes a significant health burden on patients. The pathogenesis of COPD is complex and has not been fully elucidated. Currently， Western medicine is commonly used in clinical treatment， which often yield suboptimal results and may lead to adverse reactions and drug resistance. Therefore， finding an effective and safe treatment method is a crucial focus in medical research. With the ongoing advancement in disease research， many scholars have discovered that traditional Chinese medicine （TCM） can target various signaling pathways such as nuclear factor-kappa B （NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， mitogen-activated protein kinase （MAPK）， neurogenic locus notch homolog protein （Notch）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， transforming growth factor-β （TGF-β）/Smad， secreted glycoprotein （Wnt）， Hippo， and nuclear factor erythroid 2-related factor 2 （Nrf2）. By influencing these pathways， TCM can affect airway mucus secretion， inhibit inflammation and oxidative stress， alleviate airway and microvascular remodeling， and regulate apoptosis and autophagy， ultimately reducing disease symptoms and improving lung function. TCM has thousands of years of clinical practice experience in treating COPD， demonstrating significant efficacy. Therefore， delving deeply into this from a cellular and molecular perspective can provide a reliable theoretical basis for the clinical application of TCM in treating COPD. However， systematic summaries of how TCM regulates COPD-related signaling pathways are scarce. This article aimed to extensively review and summarize recent literature in China and abroad on interventions of TCM monomers or compound prescriptions in COPD， identifying multiple related pathways to provide new insights for future clinical formulation and experimental research. Integrating basic TCM theories with modern pharmacological research mechanisms can jointly propel the development of TCM in the prevention and treatment of COPD.
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Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.
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Myocardial fibrosis （MF） is a prevalent pathological process in a spectrum of cardiac conditions， including myocardial infarction， hypertensive heart disease， and dilated cardiomyopathy. It is marked by an overabundance of extracellular matrix deposition， diminished myocardial compliance， and impaired cardiac function， which can lead to arrhythmias and sudden cardiac death. The current therapeutic approach primarily aims to suppress the progression of fibrosis， yet the therapeutic outcomes are poor. The pathogenesis of MF involves multiple signaling pathways， including the transforming growth factor-beta （TGF-β）/Smads signaling pathway， nuclear factor-kappa B （NF-κB） signaling pathway， phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， and mitogen-activated protein kinase （MAPK） signaling pathway. Traditional Chinese medicine （TCM） boasts a rich history in the treatment of cardiovascular diseases， offering distinctive benefits such as minimal side effects and high safety， and it has demonstrated promising therapeutic effects in the treatment of MF. In recent years， research has turned its attention to the application of TCM in modulating the signaling pathways associated with MF. It has been demonstrated that TCM can modulate the MF-related signaling pathways to exert anti-inflammatory effects， regulate cellular autophagy， cell proliferation， and apoptosis， reduce myocardial oxidative stress and damage， and inhibit the activation of fibroblasts and collagen synthesis， thereby exhibiting the potential to mitigate or even reverse the progression of MF. Experimental research and clinical observations indicate that TCM formulas such as Yixin Futing decoction， Luhong prescription， Zhilong Huoxue Tongyu capsules， and Kangjian Yixin prescription can effectively ameliorate MF and enhance cardiac function through the multi-component regulation of multiple cellular pathways. Specific TCM constituents， including isoliquiritigenin and astragaloside， have been shown to inhibit the expression of TGF-β1， thereby disrupting the Smad signaling pathway. Compounds like glycyrrhizic acid and allicin can suppress the NF-κB signaling pathway and curtail collagen synthesis in myocardial cells， and forsythoside can activate the PI3K/Akt signaling pathway， contributing to its anti-fibrotic effects.
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Lung cancer has the highest incidence and mortality rate among all cancers in China， with its complex and variable nature， long treatment duration， and often poor prognosis. Currently， the treatment of lung cancer mainly employs classical therapies such as surgery， radiotherapy， and chemotherapy， but some patients may experience a series of adverse reactions， which affect their quality of life， survival period， and treatment outcomes. As reported， oxidative stress is one of the important pathogenic factors of lung cancer， affecting its occurrence and development. Oxidative stress is a state of imbalance between oxidative products and antioxidant defense mechanisms in the body. The intervention of oxidative stress in the occurrence and development of lung cancer is related to multiple signaling pathways， including the Kelch-like ECH-associated protein 1 （Keap1）-nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and nuclear factor-κB （NF-κB） signaling pathway. Currently， researchers in China and abroad have conducted extensive studies on the occurrence and development of lung cancer and the pathophysiological mechanisms of drug intervention. The results have shown that oxidative stress plays an important role in the occurrence and development of lung cancer. Chinese medicine monomers and compounds can regulate oxidative stress levels and intervene in related signaling pathways， thereby inhibiting or delaying the occurrence and development of lung cancer. Based on this， this article mainly summarized the relevant signaling pathways regulating oxidative stress intervention in lung cancer in recent years， and also reviewed the latest research on Chinese medicine monomers and compounds in regulating oxidative stress to treat lung cancer， aiming to provide new ideas for research on drug treatment of lung cancer and clinical drug development， as well as to provide references and guidance for further in-depth mechanistic studies in the future.
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Objective To study the effect of formononetin on the cell damage of glucose/oxygen deprivation/reoxy-genation glyconeurons via the PARP1 signaling pathway,and to offer theoretical support for the use of Caragana isoflavones in the treatment of cerebral ischemia-reperfusion injury.Methods In mouse neurons(HT22),a model of Oxygen-glucose deprivation/reoxygenation(OGD/R)was created.Western blot was used to detect the expres-sion of PARP1 and PARG in HT22 neurons at various time points of glucose-oxygen deprivation/reoxygenation,and the optimal time point of pathway modification was chosen.After OGD/R,HT22 cells were treated with form-ononetin,PARP1 inhibitor(PJ34),and PARG inhibitor,and six groups were developed:control group,control group+formononetin group,OGD/R group,OGD/R+formononetin group,OGD/R+PJ34 group,OGD/R+PARG inhibitor group.HT22 cells were grown normally without OGD/R therapy in the control group.The expres-sion levels of apoptotic factors and associated proteins in each group were determined using immunofluorescence and Western blot.Results PARP1 pathway was activated most obviously in HT22 cells after 3 hours of glucose and ox-ygen deprivation/reoxygenation.Under the condition of OGD/R 3 h,treatment with formononetin,PJ34 or PARG inhibitor could increase E3 ubiquitin ligase(Iduna),inhibit the expression of PARP1 and PARG pathway proteins,reduce the expression of AIF and P53,and increase the phosphorylation level of AKT protein.Conclusion Form-ononetin can block the PARP1/AIF/Akt signaling pathway by raising the expression of Iduna protein in the pres-ence of OGD/R,hence decreasing the damage to HT22 mouse neurons.
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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.
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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.
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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.
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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.
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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.
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Animales , Ratones , Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Glucosa/farmacología , Osteoblastos/efectos de los fármacos , ARN Mensajero , Transducción de Señal , Teriparatido , Línea CelularRESUMEN
Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.
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Niño , Humanos , Femenino , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular , Medicina Tradicional China , FN-kappa B , RiñónRESUMEN
Fluorine is widely present in nature, and long-term excessive intake of fluoride by the body can cause damages to bone tissues such as teeth and bones, as well as non bone tissues and organs such as nervous, cardiovascular, digestive and immune systems. Fluoride can cause apoptosis and autophagy of spleen lymphocytes, ultimately leading to damage to the structure and function of spleen. This article reviews the research progress of signaling pathways related to fluoride induced spleen immune function damage, in order to provide a theoretical basis for molecular mechanism study.
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Objective To investigate the role and mechanism of miRNAs in alcoholic liver injury in rats.Methods Thirty male SD rats were randomly divided into model and control groups.The model group was gavaged with 56%liquor and the control group was gavaged with distilled water for 8 weeks.Liver tissue was collected,miRNAs were analyzed,and target genes of differentially expressed miRNAs were predicted by a rat miRNA chip.Gene ontology(GO)and KEGG pathway enrichment analysis were used to understand the function of differentially expressed miRNA target genes.A differentially expressed miRNA-mRNA-pathway regulatory network was constructed using Cytoscape to further screen important regulatory miRNAs versus important pathways.RT-qPCR was performed for selected miRNAs to validate the expression analysis.Results Twelve differentially expressed miRNAs(P<0.05,Fold change≥2)were screened out,including two upregulated and 10 downregulated miRNAs by comparative analysis of microarray data between model and control groups.GO classification annotation of differential miRNA target genes showed close associations between differentially expressed miRNAs and biological functions such as signal transduction,metabolic processes,antioxidant activity,cell killing,enzyme regulatory activity and biological regulation.Differentially expressed miRNA target genes in KEGG pathway analysis revealed that the AMPK signaling pathway,PI3K-Akt signaling pathway,Hippo signaling pathway,Wnt signaling pathway,cancer,autophagy,insulin resistance,Ras signaling pathway,and other signaling pathways might play major regulatory roles in alcoholic liver injury lesions.Hub miRNAs and pathways screened by constructing the differentially expressed miRNA-mRNA-pathway regulatory network were miR-145-5p,miR-107-3p,miR-297,Hippo signaling pathway,cancer,PI3K-Akt signaling pathway,and AMPK signaling pathway.qRT-PCR validated the gene expression trends,and gene chip result were consistent.Conclusions We established an miRNA profile of alcoholic liver injury in rats,which suggests that miR-145-5p,miR-107-3p,and miR-297 play major roles in the process of alcoholic liver pathology.
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@#Pyroptosis is an important mechanism leading to secondary brain injury （SBI） after intracerebral hemorrhage （ICH）， which can be classified into the inflammasome-dependent classical pyroptosis pathway and the caspase-4/5/11-dependent non-classical pyroptosis pathway. GSDMD and GSDME of the gasdermin family are the key effectors of pyroptosis and bind to lipids on cell membrane to induce the formation of membrane pore. Interleukin-1β/-18 is a downstream inflammatory factor that mediates inflammatory injury after pyroptosis. This article reviews the key proteins in the pyroptosis pathway and the mechanism of action of the pyroptosis signaling pathway after ICH.
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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'.
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Cancer is difficult to cure because of its heterogeneity, drug resistance and easy recurrence and metastasis. Revealing the molecular mechanism of cancer genesis and development, identifying new diagnostic markers and molecular therapeutic targets are undoubtedly effective strategies to solve the problems of early diagnosis, treatment and improvement of prognosis of cancer patients. More and more studies have shown that long non-coding RNA (IncRNA) is specifically expressed in human cancer and is a key regulator of cancer occurrence and development. Cytoskeleton regulator RNA (CYTOR) is a carcinogenic lncRNA found in recent years. CYTOR is highly expressed in many types of cancer and regulates the development of cancer through a variety of pathways, which may be an effective biomarker for early cancer diagnosis, molecular targeted therapy and prognosis assessment. This paper reviews the molecular regulatory mechanism and related biological characteristics of CYTOR in human cancer, in order to provide new scientific reference for clinical cancer diagnosis and treatment.
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Energy imbalance is eonsidered an important driver of human diseases. As an important energy sensor, AMPK plays a central role in maintaining energy homeostasis, making it a key target for disease prévention and treatment. As a new type of cell death, ferroptosis is related to the pathophysiologieal process of many diseases, and AMPK-related signaling pathway is an important way to regulate iron death. Understanding which pathway AMPK induces or inhibits ferroptosis will provide new ideas for the treatment of diseases in the future and provide new targets for new drug research. In this paper, we review the related litera-tures and explore the signaling pathways of AMPK regulating ferroptosis, wïth a brief description of the application of AMPK-mediated ferroptosis related signaling pathways in diseases, hoping to provide reference for later research.
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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.