Abstract: Objective To predict the mechanism of Shenshuai Prescription (SSR) in chronic kidney disease(CKD)-related myocardial injury using network pharmacology and molecular docking method. Methods We used the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and Herb herbal medicine identification database (http:/ / herb. ac. cn/ ), and the SwissTargetPrediction database to screen target information of active ingredients. We then used the UniProt database to screen for human targets and standard gene names. A drug active ingredient target network diagram was constructed using Cytoscape 3. 7. 2 software, and the GeneCards database was used to collect disease-related targets. The “ Shenshuai Recipe” against CKD myocardial injury gene target database was established using Venny 2. 1, and the STRING database was used to build the main component target interaction network and screen key targets. Cytoscape 3. 7. 2 software was imported for topology analysis and a protein-protein interaction network diagram was constructed. Finally, the DAVID platform was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) biological function annotation. Results After screening, there were 252 active compounds in SSR and 649 common targets of SSR and CKD myocardial injury, among which AKT Serine/ Threonine Kinase 1 (AKT1), Tumor Necrosis Factor (TNF), Mitogen-Activated Protein Kinase 3 (MAPK3), and Vascular Endothelial Growth Factor A (VEGFA) may be important targets of SSR in treating CKD myocardial injury. GO analysis identified 1485 Biological process items, 176 Cell component items, and 386 Molecular function items, of which plasma membrane, cytosol, and cytoplasm had the largest number of enriched genes, and 313, 304, 276 genes were distributed respectively. KEGG analysis indicated that HIF-1α, Lipid and atherosclerosis, AGE-RAGE signaling path in diagnostic complexes, phosphoinositide 3-kinase (PI3K)-AKT, and insulin resistance pathways might be involved in the mechanisms of SSR in treating CKD myocardial injury. Conclusions SSR might play a role in cardiorenal protection by participating in multiple mechanisms, including improving insulin resistance, improving lipid metabolism, antiatherosclerosis, and regulating the expression of inflammatory factors and vascular endothelial growth factor, with the PI3K/Akt and mitogen-activated protein kinase pathways being potentially important signal regulation pathways.
Abstract: 【Abstract】Objective To propose the formation of salt-sensitive hypertension and heart cell damage. Methods: Wistar rats, capsaicin was injected and high salt diet was feeded, the model of salt-sensitive hypertension was established. the change of heart histopathology were observed, spectrophotometry to detect heart iNOS activity and NO content; immunohistochemistry was performed to detect the expression of eNOS and iNOS protein in heart, the expression of eNOS and iNOS mRNA in heart was determined by RT-PCR, the level of apoptosis was assessed by single cell gel electrophoresis. Results: The rats body weight was not significant difference among groups at the end of the experiment (P>0.05). The capsaicin-high salt diet group systolic blood pressure was significantly higher than the other three groups (P<0.05) in 2, 3, 4 weeks. Capsaicin-high salt diet group cardiac muscle cell hypertrophy, muscle fiber disarrangement, nuclei arranged in irregular. The activity of iNOS and level of NO in capsaicin-high salt diet group significantly were higher when compared with control group. eNOS protein and eNOS mRNA significantly decreased compared with control group (P <0.01) iNOS protein and iNOS mRNA of capsaicin-high salt diet group were significantly increased compared with control group (P <0.01) in heart. The number of apoptotic cells of capsaicin-high salt diet group significantly increased compared with control group (P <0.05). Conclusions: The decreased express of eNOS mRNA and protein was related with the forming of salt-sensitive hypertension. The increased express of iNOS mRNA and protein could produce a large number of NO in heart. NO may make the cell apoptosis increasing and the damage of heart in salt-sensitive hypertensive rats.
Abstract: Objective To observe the therapeutic effect of Zhenwu decoction on myocardial pathomorphology and cardiomyocyte apoptosis in rats with heart failure induced by coronary artery ligation, and to explore its effect on apoptosis- related proteins and the PI3K-AKT signaling pathway. Methods At 4 weeks after the operation, surviving rats were randomly divided into six groups with seven rats in each group as follows. (1) Sham operation group: normal saline was administered intragastrically for 28 days at 4 weeks after the operation. (2) model group: normal saline was administered intragastrically for 28 days after 4 weeks. (3) positive control group: 5 mg / kg losartan potassium was administered for 28 days after 4 weeks. ( 4) Zhenwu decoction low dose group: after 4 weeks, 6 g / kg Zhenwu decoction crude drug was administered for 28 days. ( 5 ) Zhenwu decoction middle dose group: 12 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. (6) Zhenwu decoction high dose group: 18 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. Changes in the electrocardiogram, color ultrasound, cardiomyocyte apoptosis, myocardial morphology, PI3K, AKT1 and p-AKT1 protein levels in myocardial tissue, immunohistochemical changes of Bax, Bcl-2, caspase 3, 8, 9 and BNP in the abdominal aorta were observed before and after modeling. Results ( 1) The ST segment of the heart failure model was elevated after coronary artery ligation, indicating that model establishment was successful. (2)The left ventricular mass index and BNP level of heart failure rats were increased significantly, and LVEF and LVFS were decreased significantly, whereas the left the ventricular mass index, BNP level, LVEF and LVFS were improved in the other groups. ( 3) Myocardial fibers in the model group were disordered and broken accompanied by cardiomyocyte swelling, hypertrophy. and inflammatory cell infiltration, which were relieved to various degrees in the other groups. Apoptosis in the model group was significant, which was alleviated after by Zhenwu decoction and positive control group drugs. (4)Compared with the model group, Bcl-2 was increased, and Bax and Caspase 3, 8, 9 were decreased in each treatment group. There was no significant difference in protein expression between Zhenwu decoction middle dose and sham operation groups. (5)Compared with the sham operation group, PI3K, p-AKT1 and AKT1 expression in the model group was increased, and Zhenwu decoction suppressed protein expression of PI3K, p- AKT1 and AKT1. Conclusions Zhenwu decoction reduces cardiomyocyte apoptosis and myocardial pathological changes in HF rats by regulating the PI3K-AKT pathway, enhancing myocardial contractility, and delaying the progression of heart failure.
Abstract: Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation. Current research has mainly focused on the role of ferroptosis in the field of cancer, but increasing evidence shows that ferroptosis is also related to the occurrence of infectious diseases. Ferroptosis has accordingly been detected in cases of COVID-19, tuberculosis, and cryptococcal meningitis, as well as other diseases.This article reviews the role of ferroptosis in infectious diseases, to provide new ideas for the prevention and treatment of ferroptosis-related infectious disease
Abstract: Objective To analyze the dynamic changes to disease activity, colonic inflammation, histopathology,and serum cytokine levels in mice with chronic ulcerative colitis ( UC). Methods For UC induction, 2. 5% dextran sodium sulfate solution was provided ad libitum for 5 days, and to model remission, tap water was supplied for another 5 days in one induction cycle. Disease activity index (DAI), colon length, and pathological changes to colon tissue were determined. The levels of myeloperoxidase (MPO) in colon tissue and of cytokines such as IL-1β in serum and colon were detected. Results During the three cycles, disease activity was aggravated and colon length shortened in mice during the induction periods, both of which were relieved during the remission periods. The blood appeared was observed in the stool was earlier in cycles 2 and 3. The number of mice with stool blood increased, and their body weight decreased by a small amount briefly, then recovered rapidly. The degree of histopathological damage to the colon and MPO content in cycles 1 and 3 increased in the induction periods and decreased in the remission periods, with the magnitude of change smaller than that of the change in DAI values; and they increased in the remission period of cycle 2. During induction, the spleen index and serum levels of IL-1β, IL-6, and IL-17A increased continuously and were higher than those in the control group at the end of the experiment. Levels of TNF-α were increased in the induction periods and decreased in the remission periods,and the trend in IL-10 change was similar to that of TNF-α. TGF-β content increased and then decreased and was higher than that in the control group at the end of cycle 3. The colon contents of IL-1β, IL-6, and IL-17A showed similar trends of increasing and then decreasing, but there was no significant change in colon TNF-α. The concentration of IL-10 decreased during the induction periods and increased during the remission periods. Conclusions During the induction of chronic UC in mice, the symptoms of hematochezia and systemic inflammatory reactions gradually increased, and the mice showed an increase in tolerance and ability to resist mortality, weight loss, and histopathological injury to the colon. The onset and remission of colonic histopathological damage lags behind symptomatic changes, and there is a gradual shift in colonic inflammation to a pattern dominated by polymorphonuclear neutrophils (PMN) activation.
Abstract: The major histocompatibility complex (MHC) is closely related to immune regulation. MHC shows distinct genetic polymorphism, and there are also species differences in MHC restriction. The human MHC is called human leukocyte antigen (HLA), and the mouse MHC is called H-2. The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response. MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models. The development of HLA Ⅰ transgenic mouse model went through three stages, at present, the strategy of knocking out H-2K b and H-2D b or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules. In the construction of an HLA Ⅱ transgenic mouse model, the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted. With the optimization of construction strategies, MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment, and genetic disease-association studies, becoming a powerful tool for preclinical trials. In this paper, we summarize the relevant data on MHC transgenic mouse models, as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.
Abstract: Objective To establish a model of long-term atrazine (ATR)-induced liver injury in mice and to evaluate the hepatotoxic effects induced by ATR. Methods C57BL/ 6-N male mice were randomly divided into a control group and 1. 5 mg / L and 150 mg / L ATR dose (ATR-L, ATR-H) groups. After 35 and 63 days, serum liver function biochemical indexes and inflammatory factors were detected, the hepatosomatic ratio was calculated, and the histopathology and ultrastructure of the liver were observed. Lipid peroxidation levels and antioxidant capacity, the activities of major phase I metabolic enzymes and phase II detoxification enzymes, and the expression of related proteins in liver tissues were detected. Results Compared with the control group, the ATR groups showed significant changes in the AST/ ALT ratio,levels of pro-inflammatory factors CCL2, TNF-α and IL-6, H2O2 content and activities of the metabolic enzymes NCR,CYT b5, and UDPGT ( P<0. 05). In the 150 mg / L ATR group, GGT content, peroxide levels ( as indicated by malondialdehyde), and CYP1A2 expression were significantly increased (P<0. 01), while GSH content was significantly decreased (P<0. 05), and hepatocyte injury and mitochondrial vacuolation were more serious when compared to control and 1. 5 mg / L groups. Conclusions In a mouse model of low-dose ATR liver injury, both 1. 5 mg / L and 150 mg / L ATR exposure induced liver injury in mice, with 150 mg / L ATR inducing the maximum metabolic toxicity in the liver after 63 days
Abstract: Objective To study the impact of a Western diet-type feed on biological indicators and histopathology in APOE- / - mice. Methods Forty-eight female and 48 male APOE- / - mice, and 48 female and 48 male C57BL/ 6J mice were divided into eight breeding groups: APOE- / - breeding feed group, APOE- / - Western dietary feed group, C57BL/ 6J breeding feed group, and C57BL/ 6J Western dietary feed group (24 male and 24 female mice per group). Mice were fed the respective diets from 3 weeks until the end of the experiment at 20 weeks. After the experiment, serum was collected for measurement of biochemical indicators. Aortas were removed for oil red O staining and gross examination and the aorta root was paraffin sectioned and stained with hematoxylin and eosin. Results A Western diet did not significantly increase body weight in APOE- / - mice, but did significantly improve the blood lipid index and total cholesterol, low-density lipoprotein,and high-density lipoprotein levels, and promoted the formation of atherosclerotic plaques. Male mice were suitable for modeling gross aortic plaques while female mice were suitable for modeling aortic arch root plaques. Conclusions A Western diet can promote atherosclerosis in APOE- / - mice, increase the aortic plaque area ratio, shorten modeling time,and improve modeling uniformity.
Abstract: Digestive tract tumors are currently one of the most common types of cancer, including esophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Their prognoses are poor and the treatments require further improvement. Caveolin-1 (CAV1) has a dual regulatory effect on digestive tract tumors as a tumor suppressor and cancer promoter. CAV1 plays a major role in cell proliferation, invasion, metastasis, angiogenesis,and drug tolerance of digestive tract tumors. The regulation of CAV1 protein and its related signaling pathways may be a strategy for the treatment of digestive tract tumors. This review analyzes the relationship between CAV1 and digestive tract tumors in terms of structure, function, expression regulation, regulation of epithelial-mesenchymal transition, and drug resistance in digestive tract tumors to provide new ideas for the diagnosis and treatment of digestive tract tumors.
Abstract: Mitochondria-associated membranes ( MAMs ) are a subcellular compartment involved in the communication and material exchange between the mitochondrial outer membrane and endoplasmic reticulum membrane.MAMs perform various biological processes in cells under different conditions. MAM-dysfunction-mediated calcium homeostasis imbalance, endoplasmic reticulum stress, mitophagy defects, mitochondrial fission / fusion dynamics imbalance, lipid metabolism disorders, and inflammatory responses are key pathogenic factors in Alzheimer’ s disease (AD). This article reviews the structure and function of MAMs, their involvement in AD pathology, and drug intervention targets, and discusses the role of MAMs in the pathogenesis of AD and the latest research into their mechanisms, to provide new ideas for the prevention and treatment of AD.
Abstract: Objective We investigated the effects of ICAM5 in the hippocampus on the alcohol drinking preference of mice, and the potential mechanisms. Methods An alcohol two-bottle choice model was developed in 8-week-old male C57BL/ 6J mice, which were randomly divided to two groups: water group and alcohol group. The protein expression of ICAM5 in the hippocampus, amygdala, and medial prefrontal cortex was detected. An ICAM5-overexpressing adeno-associated virus was constructed and injected into the hippocampus by stereotaxic method. The expression level of ICAM5 protein in the hippocampus was detected by immunofluorescence and Western blot. We then detected the alcohol preference and locomotor activity of mice with a conditioned place preference (CPP) experiment, open field test, and lossof-righting reflex test. Western blot analysis was used to identify the neuron F-actin / G-actin ratio. Using Golgi staining, the morphology of dendritic spines was identified. Results The expression of ICAM5 in the hippocampus of alcohol two-bottle choice model mice in the alcohol group was considerably lower than that of the water group ( P<0. 001). The specific expression of ICAM5 in the hippocampus of mice was observed by fluorescence microscopy. In the open field experiment,the staying time and moving distance of the AAV-ICAM5 group were significantly increased compared with those of the control group ( P<0. 01). In the CPP experiment, the residence time of AAV-ICAM5 mice in the alcohol-paired compartment was significantly lower than that of control mice ( P<0. 001). In the loss-of-righting reflex experiment,overexpression of ICAM5 significantly reduced sedation latency ( P<0. 01), but significantly shortened the duration of sedation (P<0. 001). Compared with AAV-mCherry +Water group, the ratio of F-actin / G-actin in the hippocampus was significantly increased after drinking ( P<0. 01 ), but after ICAM5 overexpression, their F-actin / G-actin ratio was significantly decreased (P<0. 001). Compared with AAV-mCherry + Water group, the density of dendritic spines in the hippocampal CA1 region was increased (P<0. 001), but the density of dendritic spines in the AAV-ICAM5+Alcohol group was significantly decreased (P<0. 01). Conclusions ICAM5 modulated the expression of cytoskeleton proteins to change the structural plasticity of dendritic spines, which contributed to alcohol-drinking and locomotor behavioral changes in mice.
Abstract: Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies. Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group, and cyclophosphamide +fungal infection low, medium, and high dose groups, with 12 animals in each group. General clinical observations were performed daily, and the serum levels of immunoglobulin (Ig)G and IgM and galactomannan (GM) were detected by ELISA on the 3rd and 7th days of modeling. Simultaneously, the ratio of CD4+ and CD8+cells, content of white blood cells (WBCs) and neutrophils (Neu) in peripheral blood, the Aspergillus niger load in alveolar lavage, and morphological changes to rat lung tissue were observed. Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling, and rats in the cyclophosphamide + fungal infection group also had shortness of breath and audible wet rhonchi in the lungs. Compared with the normal control group, rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+, WBC, Neu, IgG, and IgM in the blood, and their proportion of CD8+cells was significantly higher ( P<0. 05, P<0. 01 ). Compared with the cyclophosphamide control group, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly reduced blood levels of IgG, IgM, and CD4+ cells (P<0. 05, P<0. 01); while the cyclophosphamide+fungal infection low-, medium-, and high-dose groups had significantly reduced blood levels of WBC and Neu (P<0. 05, P<0. 01). Additionally, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly increased blood CD8+ cells (P<0. 05, P<0. 01), Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide + fungal infection low-, medium-, and high-dose groups compared with the cyclophosphamide control group (P<0. 05, P<0. 01). The lung tissues of the cyclophosphamide+fungal infection low-, medium-, and high-dose groups showed mycelial distribution and destruction of alveolar epithelium, increase of bronchial epithelial cup cells in the alveoli, and infiltration of inflammatory cells, and the degree of lesions was positively correlated with the modeling dose. Conclusions In this study, we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease. The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time, confirming that cellular immunity plays an important role in the pathogenesis of the disease. At the same time, Ig can also affect the development of invasive pulmonary aspergillosis, and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.
Abstract: Skeletal muscle wasting refers to a loss of skeletal muscle mass and function. Mitochondrial quality control (MQC) is the basis by which normal physiological mitochondrial function is maintained and mainly involves the regulation of mitochondrial biogenesis, mitochondrial dynamics ( fission / fusion), and mitophagy. MQC maintains muscle homeostasis by regulating the relative stability of mitochondrial shape, quantity, and quality. As an economical and effective treatment for muscular atrophy, exercise interventions are widely used, but the relationship between exercise intervention and MQC is not clear. This paper discusses the role of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in skeletal muscle atrophy and related molecular targets. We thoroughly analyze the mechanisms by which MQCmediated exercise can improve the skeletal muscle atrophy caused by aging, disuse, and cancer cachexia in order to provide theoretical guidance for intervention.
Abstract: Ferroptosis is a newly cell death mode discovered in recent years, involving in a variety of pathophysiological processes, such as ischemia reperfusion injury, neurodegenerative diseases and tumors, etc. At present,there is a lack of effective method to prevent and treat ischemic stroke worldwide, and ferroptosis which is involved in cerebral ischemia reperfusion injury. 50 articles were included in this paper after searching the related literature, which published in databases such as PubMed, Wanfang, VIP and CNKI in recent years. Discussing the iron metabolism and the concept, mechanism and regulation of ferroptosis, the role of ferroptosis in the mechanism of cerebral ischemia reperfusion injury, and the method of inhibiting ferroptosis, this paper attempts to provide reference for finding a new potential treatment for ischemic stroke from the direction of inhibiting ferroptosis.
Abstract: Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury (CCI). Methods Fifty-six SD rats were divided randomly into eight groups: normal group, sham group, model 1 group, model 2 group, tuina 1 group, tuina 2 group, tuina 1 + transient receptor potential vanilloid-1 (TRPV1) antagonist group, and tuina 2 + transient receptor potential ankyrin 1 (TRPA1) antagonist group. The model, tuina, and tuina + antagonist groups were established with minor CCI models. The tuina and tuina + antagonist groups received the three-method three-point intervention ( point method, dial method, kneading method, Yinmen point, Chengshan point, Yanglingquan point) 7 days after modeling. The model and sham groups were subjected to grasping restraint, and the normal group received no intervention. After the respective interventions, each group was tested for changes in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) to detect different types of pain. The nitric oxide (NO) content of the dorsal root ganglion (DRG) was determined by the nitrate reductase method, and changes in protein and gene expression levels of components of the TRPV1 / TRPA1-NO-cGMPprotein kinase G (PKG) signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay, Western blot, and qPCR. Results Compared with the model group, MWT and TWL were prolonged in the tuina 1 and tuina 2 groups. Expression levels of TRPV1, TRPA1, NO, soluble guanylate cyclase-β, cGMP, and PKG1 in the DRG were significantly decreased in the tuina 1, tuina 2, tuina 1 + TRPV1 antagonist, and tuina 2 + TRPA1 antagonist groups. Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention. Tuina can exert immediate and continuous analgesic effects via the TRPV1 / TRPA1-NO-cGMP-PKG signaling pathway.
Abstract: Pulmonary hypertension ( PH ) is a progressive disease characterized by pulmonary vascular remodeling. Current treatments for PH remain suboptimal, and there is an urgent need to better decipher the underlying pathomechanisms to identify new therapeutic targets. MicroRNA (miRNA) are key components in the post-transcriptional machinery that mediates cellular functions and mainly act by regulating the expression of downstream target genes.Numerous in vivo and in vitro studies have demonstrated the involvement of miRNA and their regulators in PH development.However, there is no unified model for the mechanism of miRNA’ s regulation of pulmonary vascular remodeling. Therefore, this article provides a review on the mechanisms of miRNA in PH characterized in recent years.
Abstract: Objective To construct a patient-derived pancreatic tumor organoid ( PDO) and evaluate its effectiveness. Methods We collected fresh surgical specimens from pancreatic cancer patients for PDO culture and compared the pathological and genetic characteristics of the PDO model with those of primary tumors. The PDO model was used to evaluate the efficacy of clinical chemotherapy drugs, and the effectiveness of the model was assessed. Results A PDO model of pancreatic cancer was successfully established. Histomorphological analysis indicated that the PDO model maintained the basic pathological characteristics of the primary tumor. Whole-exon sequencing showed that both the organoids and original tumor tissue remained consistent in their gene mutation type and characteristics. Drug screening tests revealed that the PDO model had good sensitivity to gemcitabine and irinotecan. Conclusions A pancreatic cancer PDO was successfully constructed that reflected the histological and genetic characteristics of the original tumor. The model was shown to be effective for drug sensitivity experiments in vitro and is expected to have implications for precision medicine assays.
Abstract: Objective To study the role of ubiquitin-conjugating enzyme 9 ( UBC9) in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier (SUMO) modification. Methods First, the effects of homocysteine at different concentrations (0 μmol / L, 50 μmol / L, 100 μmol / L, 150 μmol / L and 200 μmol / L) on the viability and pyrodeath of mouse macrophages (RAW264. 7) were detected by CCK-8 and Western blot. Western blot was used to detect the expression levels of UBC9, SUMO-1, and the inflammatory cytokine IL-1β in different groups of cells. qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9, pyrogen-related protein, and SUMO-1 after RNA interference. Results After stimulation with 100 μmol / L homocysteine, the effect of macrophage activity was minimal, and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression (P<0. 05). Compared with the Control group, the Hcy group’ s expression of IL-1β and SUMO-1 was increased (P<0. 01). Compared with the Control group, the Hcy group’ s UBC9 protein and mRNA levels were increased (P<0. 05). The expression of NLRP3, Caspase-1, IL-1β, UBC9, and SUMO-1 was decreased in the siUBC9 + Hcy group compared with the si-NC+Hcy group (P<0. 01). Conclusions Homocysteine induces pyroptosis in macrophages, and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.
Abstract: Liver fibrosis is a key pathological process in the progression of chronic liver disease to cirrhosis and even liver cancer. The occurrence of liver fibrosis is a highly integrated and dynamic pathological process result ing from the interactions of many cells and cytokines. The Notch signaling pathway is an evolutionarily conserved intercellular signal transduction mechanism that plays important roles in regulating the development and tissue renewal of multicellular animals.Multiple studies have shown that Notch signal transduction participates in the formation of liver fibrosis in a variety of ways.Therefore, this paper reviews the role of Notch signaling in cells involved in the formation of liver fibrosis to explain the function of this signaling pathway in liver fibrosis.
Abstract: Chemotherapy resistance in leukemia is an urgent clinical therapeutic challenge. Ferroptosis is a unique mode of cell death driven by iron-dependent phospholipid peroxidation. Leukemia is characterized by increased oxidative stress and iron overload, suggesting that leukemia cells might be susceptible to ferroptosis and indicating a possible therapeutic approach. Ferroptosis has been extensively studied in recent years and used in the treatment of various types of leukemia. Several studies have demonstrated an association between the regulatory pathways of ferroptosis and the mechanisms of leukemia drug resistance. The induction of ferroptosis through different pathways can effectively reduce the resistance of various types of leukemia cells to chemotherapeutic drugs, and thus improve their clinical efficacy. In this article, we review the regulatory mechanisms of ferroptosis and analyze the association between oxidative stress and iron metabolism pathways of ferroptosis and the mechanism of leukemia drug resistance. We also summarize the experimental studies and clinical applications of ferroptosis for the treatment of various types of drug-resistant leukemias, with the aim of providing new ideas and directions for the study of ferroptosis and a new strategy to reverse chemotherapy resistance in patients with leukemia in the future.
