Bta-miR-149-3p suppresses inflammatory response in bovine Sertoli cells exposed to microcystin-leucine arginine (MC-LR) through TLR4/NF-kB signaling pathway.

This study explored the regulatory role of bta-miR-149-3p in the inflammatory response induced by microcystin-leucine arginine (MC-LR) exposure in bovine Sertoli cells. The research endeavored to enhance the comprehension of the epigenetic mechanisms underlying MC-LR-induced cytotoxicity in Sertoli cells and establish a foundation for mitigating these effects in vitro. In this study, we elucidated the regulatory mechanism of bta-miR-149-3p in the MC-LR-induced inflammatory response by verifying the target gene of bta-miR-149-3p through luciferase assays and treating the cells with a bta-miR-149-3p inhibitor for 24 h. The results demonstrate that nuclear factor κB (NF-κB) acts as a downstream target gene of bta-miR-149-3p, which inhibits the MC-LR-induced inflammatory response in bovine Sertoli cells. This inhibition occurs by regulating the downregulation of tight junction constitutive proteins of the blood-testis barrier (BTB) through the suppression of the TLR-4/NF-κB signaling pathway (p < 0.05) and the up-regulation of the adhesion junction protein ß-catenin (p < 0.05). Notably, MC-LR exposure resulted in the up-regulation (p < 0.05) of inflammatory cytokines (IL-6, IL-1ß, and NLRP3) and the down-regulation (p < 0.05) of BTB tight junction constitutive proteins (ZO-1, Occludin) in Sertoli cells. Furthermore, the BTB constitutive protein ZO-1 exhibited significant down-regulation in Sertoli cells pretreated with the bta-miR-149-3p inhibitor compared to controls (p < 0.05), while Occludin showed no significant difference from CTNNB1 (p > 0.05). In summary, our findings suggest that bta-miR-149-3p suppresses the MC-LR-induced inflammatory response and alterations in the expression of BTB proteins in bovine Sertoli cells by inhibiting the TLR-4/NF-κB signaling pathway.

The influence of psychological resilience and nursing practice environment on nurses' moral courage: A cross-sectional study.

AIM: To determine the relationship between psychological resilience, nursing practice environment, and moral courage of clinical nurses and also the factors influencing moral courage. DESIGN: Cross-sectional study. METHODS: 586 nurses from a general hospital were selected by convenience sampling method in January 2023. The general information questionnaire, Nurses' Moral Courage Scale (NMCS), Resilience Scale, and Practice Environment Scale (PES) were measured. Hierarchical linear regression analysis was used to explore the influencing factors of clinical nurses' moral courage. RESULTS: Nurses' average moral courage score was 79.00 (69.00, 91.00). The nurses' moral courage was positively correlated with psychological resilience and nursing practice environment. Multivariate linear regression analysis showed that psychological resilience and nursing practice environment entered the regression equation, accounting for 23.4% of the total variation. Psychological resilience and nursing practice environment are the main factors affecting the moral courage of clinical nurses. Nursing managers should conduct moral courage training, develop a decent nursing practice environment, pay attention to the psychological emotions of nurses, and actively build a safe, open, and supportive atmosphere for moral behaviour.

Mechanism on Banxia Xiexintang Inducing Ferroptosis in Gastric Cancer Cells Based on Nrf2/GPX4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang （BXT） on the proliferation of human gastric cancer HGC-27， MKN-45， and AGS cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the effects of different concentrations of BXT-containing serum （5%， 10%， and 20%） on the proliferation of HGC-27， MKN-45， and AGS cells. A mitochondrial membrane potential probe （TMRE） was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion （Fe2+） content， lipid peroxide （LPO）， and superoxide dismutase （SOD） activity. Western blot was used to detect the protein expression levels of glycogen synthase3β （GSK3β）， phosphorylated GSK3β （p-GSK3β）， nuclear factor E2 related factor 2 （Nrf2）， and glutathione peroxidase 4 （GPX4）. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 （SLC7A11）， member 2 of the heavy chain solute vector family 3 （SLC3A2）， transferrin receptor 3 （TFRC）， and tumor protein （TP）53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h （P<0.01）. After 48 h of intervention with drug-containing serum， the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent， with 20% BXT having the most significant effect （P<0.01）. In terms of biochemical indicators of ferroptosis， compared with the blank group， BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential （P<0.01） and SOD activity （P<0.01） and significantly increased the contents of LPO and Fe2+ （P<0.01）， so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway， compared with the blank group， the BXT group could reduce the protein expressions of p-GSK3β， Nrf2， and GPX4 （P<0.01） in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 （P<0.05）. It could also increase the protein expression of GSK3β （P<0.01） and mRNA expression of TP53 and TFRC （P<0.05， P<0.01） in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group， the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27， MKN-45， and AGS by inhibiting the Nrf2/GPX4 pathway.

Study on mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy based on proteomics / 中国药理学通报

Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443 / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration.@*METHODS@#HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR.@*RESULTS@#HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05).@*CONCLUSION@#HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

Integrated 'omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome.

OBJECTIVE: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles. METHODS: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d). Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota. RESULTS: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota. Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose (P = 0.001), aspartic acid (P = 0.009), alanine (P = 0.007), serine (P = 0.000), threonine (P = 0.027), methionine (P = 0.023), 5-hydroxytryptamine (P = 0.008), alpha-linolenic acid (P = 0.003), eicosapentaenoic acid (P = 0.006), hypoxanthine (P = 0.000), vitamin B6 (P = 0.000), cholic acid (P = 0.013), and taurocholate (P = 0.002). Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides. CONCLUSIONS: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review).

Ferroptosis is a novel form of regulated cellular necrosis that plays a critical role in promoting cancer progression and developing drug resistance. The main characteristic of ferroptosis is iron­dependent lipid peroxidation caused by excess intracellular levels of reactive oxygen species. CUGBP ELAV­like family number 2 (CELF2) is an RNA­binding protein that is downregulated in various types of cancer and is associated with poor patient prognoses. CELF2 can directly bind mRNA to a variety of ferroptosis control factors; however, direct evidence of the regulatory role of CELF2 in ferroptosis is currently limited. The aim of the present review was to summarise the findings of previous studies on CELF2 and its role in regulating cellular redox homeostasis. The present review may provide insight into the possible mechanisms through which CELF2 affects ferroptosis and to provide recommendations for future studies.

The effect of nursing intervention on self-care self-efficacy and genes related to anxiety in patients with bone marrow transplantation.

Leukemia patients, after bone marrow transplantation, face many problems that hurt their self-efficacy in self-care. The present study aimed to determine the effect of health promotion strategies on the self-efficacy of patients undergoing bone marrow transplantation in self-care. The expression level of two genes affecting anxiety (i.e., 5-hydroxytryptamine receptor 1A (5-HT1A) and Corticotropin Releasing Hormone Receptor 1 (CRHR1)) was also investigated. For this purpose, this semi-experimental study was conducted before and after in bone marrow transplant candidate patients. Sixty patients were randomly divided into test and control groups. The test group received training on health promotion strategies, and the control group was treated according to the department's routine. Then the self-efficacy of the two groups was compared before and thirty days after the intervention. Also, the expression level of two genes was done by real-time PCR. Data analysis was done using descriptive statistics and paired t-tests, independent t-tests, analysis of covariance, and chi-square in SPSS 11.5 software. The results showed that there was no significant difference between the demographic variables of the two groups. The self-efficacy of the test group in the general scale and dimensions of adaptability, decision-making, and stress reduction increased compared to the control group and themselves before the training (p>0.001). The difference in self-efficacy scores in all dimensions before the intervention was statistically significant (p<0.05). The genetic evaluations also confirmed the obtained results. According to the expression of 5-HT1A and CRHR1 genes, the level of these genes which directly relate to anxiety were significantly decreased after intervention in the test group. In general, teaching health promotion strategies to bone marrow transplant patients can increase the confidence of these patients in taking care of themselves in the treatment process, which will ultimately lead to more survival and a higher quality of life in these patients.

Peptide photowrapping of gold-silica nanocomposites for constructing MMP-responsive drug capsules for chemo-photothermal therapy.

A multifunctional undecapeptide, YYDPLGLADYY, was designed and synthesized for the photowrapping of silica-coated gold nanorods. The obtained nanocapsules, bearing a well-defined core-shell structure, were able to encapsulate a therapeutic drug, respond to an MMP-upregulated tumor microenvironment, and achieve NIR-triggered anticancer chemo-photothermal therapy with favorable efficacy.

Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles.

Direct oxidative coupling of inert C(sp3 )-H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α-methyl substituted N-heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry.

Analysis of risk factors for thrombocytopenia in early period after pediatric liver transplantation / 中华器官移植杂志

Objective:To explore the risk factors for the occurrence of thrombocytopenia (TCP) within 2 weeks after pediatric liver transplantation (LT) and examine the relationship between the occurrence of TCP and prognosis.Methods:From January 2021 to November 2021, clinical data were retrospectively reviewed for 162 pediatric LT recipients aged under 4 years at Organ Transplantation Center of Tianjin First Central Hospital.Based upon the lowest value of platelet count at Week 2 post-operation, they were assigned into two groups of TCP (n=90) and non-TCP (n=72). General preoperative profiles, intraoperative findings, postoperative complications, types of commonly used antibiotics, anticoagulant dosing and prognosis of two groups were compared.Univariate and multivariate analyses were utilized for examining the independent risk factors for TCP.Receiver operating characteristic (ROC) curve was plotted for examining the cut-off value of independent risk factors for diagnosing TCP.Results:Among them, 90 (55.56%) developed TCP within 2 weeks post-operation and 25(15.43%) developed TCP at Day 1 post-operation.The median preoperative platelet count was 178×10 9/L and the lowest value was 65×10 9/L at Day 3(1-4) post-operation with a declining rate of 63.5% and platelet count of recipient normalized at Day 6(4-7.25) post-operation.The results of univariate analysis showed statistically significant inter-group differences in operative duration[(574.43±80.53)min vs.(526.75±72.42)min], intraoperative blood loss[400(300, 550)ml vs.320(300, 400)ml], red blood cell transfusion[2(2, 3)U vs.2(1.5, 2.0)U], preoperative platelet count[178.5(141.75, 242.5)×10 9/L vs.257 (209.75, 357)×10 9/L], postoperative infection rate[27.8%(25/90)vs.13.9%(10/72)] and dosing rates of piperacillin sodium and tazobactam sodium[8.9%(8/90)vs.25.0%(18/72)] ( P<0.05). Multivariate Logistic regression analysis revealed statistically significant inter-group differences in operative duration( P=0.008), red blood cell transfusion( P=0.01), preoperative platelet count( P<0.01) and postoperative infection rate ( P=0.02). The results of ROC curve analysis showed that the cut-off values of operative duration, red blood cell transfusion and preoperative platelet count were 535 min, 2.75 U and 183.5×10 9/L respectively.Length of ICU stay was higher in TCP group than that in non-TCP group, and the difference was statistically significant [4(3, 5) vs.3(3, 4) day, P=0.006]. Conclusions:LT children aged under 4 years with intraoperative red blood cell transfusion>2.75 U, operative duration>535 min and preoperative platelet count<183.5×10 9/L are more likely to develop post-transplantation TCP.And occurrence of TCP prolongs the length of ICU stay in pediatric recipients.

The mechanisms underlying metronomic chemotherapy and its application in advanced non-small cell lung cancer / 中华老年医学杂志

The morbidity and mortality of non-small cell lung cancer(NSCLC)are among the highest of all malignancies.The mechanisms concerning metronomic chemotherapy include anti-angiogenesis, immune microenvironment regulation, and cytotoxic effects, among others.As an alternative to traditional chemotherapy, metronomic chemotherapy has shown promising outcomes in the treatment of advanced NSCLC.Several clinical trials have explored the application of metronomic chemotherapy in the treatment of advanced NSCLC, either as a monotherapy or in combination with chemotherapy, anti-angiogenic therapy, targeted therapy or immunotherapy.This paper mainly reviews the mechanisms underlying metronomic chemotherapy and its clinical application in advanced NSCLC, in order to provide more evidence for the optimization of NSCLC treatment regimens.

The predictive value of the epithelial cell proliferation pathway genes for the prognosis of elderly non-small cell lung cancer patients receiving immunotherapy / 中华老年医学杂志

Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS: 10.9 months vs.17.1 months, HR=1.84, 95% CI: 1.09-3.08, P<0.05; mPFS: 2.8 months vs.4.2 months, HR=1.58, 95% CI: 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI: 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI: 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.

The status and influencing factors of the dyadic coping in spouses of young and middle-age cervical cancer patients undergoing synchronous radiotherapy and chemotherapy / 中国实用护理杂志

Objective:To analyze the status of the dyadic coping in spouses of young and middle-age cervical cancer patients undergoing synchronous radiotherapy and chemotherapy, and to explore the influencing factors in bi-directional of patients and their spouses.Methods:With the convenience sampling method, a total of 150 cervical cancer patients undergoing synchronous radiotherapy and chemotherapy who were hospitalized in the Radiotherapy Department of Tianjin Medical University Cancer Institute and Hospital from March 2021 to February 2022 and their spouses were selected. A cross-sectional study was conducted by the Dyadic Coping Inventory, the Lock-Wallace Marital Adjustment Test, the General Self-Efficacy Scale, the Hospital Anxiety and Depression Scale, etc. Besides, multiple linear regression was used to identify predictors of the dyadic coping in spouses of cervical cancer patients undergoing synchronous radiotherapy and chemotherapy.Results:The total score of dyadic coping, marital quality, general self-efficacy, anxiety and depression in spouses of cervical cancer patients undergoing synchronous radiotherapy and chemotherapy were (121.69 ± 19.67), (97.23 ± 25.05), (25.13 ± 5.19), (9.98 ± 3.46), (8.19 ± 4.06) points. The scores of anxiety and depression of cervical cancer patients undergoing synchronous radiotherapy and chemotherapy were (10.57 ± 3.60), (9.10 ± 4.12) points. Multiple linear regression analysis showed that factors of the patients′ anxiety and depression, spouse′s perception of marital quality, spouse′s general self-efficacy, changes in family relationship, family income, and period of radiotherapy were the main influencing factors ( P<0.01), which accounted for 55.7% of total variation. Conclusions:The level of dyadic coping in spouses of cervical cancer patients undergoing synchronous radiotherapy and chemotherapy was medium, the marriage quality remains to be further improved,and its influence factors involved in the bi-directional of patient and spouse, including patients′ anxiety and depression, the changes of the family relationship, period of radiotherapy, spouses perception of marital quality and self-efficacy and family income. Clinical medical staff can improve the level of dyadic coping in spouses of cervical cancer patients undergoing synchronous radiotherapy and chemotherapy by improving their cognition of disease, reducing the incongruence of dyadic illness appraisals, and taking multiple measures to reduce the economic burden felt of the spouses.

Mechanism of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma medicinal pair in delaying heart aging based on animal experiments and computer verification / 国际中医中药杂志

Objective:To explore the mechanism of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair in delaying heart aging based on animal experiments, network pharmacology and molecular docking. Methods:Mice were divided into control group, aging group, metformin group and TCM group according to random number table method. All the groups were injected subcutaneously by D-galactose except the control group to build the subacute aging model. Two weeks later, the metformin group was given metformin suspension (150 mg/kg), the TCM group was given Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma lyophilized powder solution (650 mg/kg), and the control group and aging group were given an equivalent volume of ultrapure water by gastric gavage, once a day, six times a week, for 10 weeks. The level of heart TERT mRNA was detected by PCR; the expression of heart p53 was observed by immunohistochemical staining; the morphology of heart tissue was observed by HE staining. TCMSP and SwissTargetPrediciton databases were used to retrieve the active components and targets of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair; TTD, OMIM, Gene, HAGR, DisGeNET and other data platforms were used to screen the targets of heart aging; after the drug and disease targets were intersected, the active components of them were collected; STRING database, Cytoscape 3.8.0 software, etc. were used to make PPI of the intersection targets, and screen out the key targets; FunRich was used to perform enrichment analysis of cellular components, molecular functions, biological processes, and biological signal pathways for key targets; Schr?dinger Maestro software was used to do the molecular docking of the screened active components and key targets, and docking results were visualized via PyMOL 2.1 software. Results:Experiment results showed that Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma could significantly ameliorate the damage of aging heart tissues, elevate TERT mRNA level, while significantly reducing the positive expression of p53. A total of 32 active components from the medicinal pair were screened, corresponding to 637 target genes. There were 263 targets for heart aging, and 67 intersection targets of drug active component targets and heart aging targets. 31 key targets were obtained after screening. Enrichment analysis showed that molecular functions were related to transcription factor activity and protein-tyrosine kinase activity. Biological processes involved signal transduction and cell communication. Signaling pathways mainly involved PDGFR-beta, PI3K-Akt, S1P1, Glypican, TRAIL, and Glypican 1. The molecular docking results showed that kaempferol, suchilactone, and ginsenoside Rg5_qt in the medicinal pair had a strong binding ability to p53. Conclusion:Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma may achieve the effect of delaying heart aging by inhibiting p53 expression, providing a foundation for further research on mechanism of invigorating qi and activating blood circulation drugs to delay heart aging.

Progress of tumor suppressor genes MLL3 in leukemia / 白血病·淋巴瘤

MLL3 is also known as lysine methyltransferase 2C (KMT2C). The mutation of MLL3 can occur in a variety of human cancers, including leukemia, liver cancer, and stomach cancer. The effect of MLL3 in different cancers is also different, for example, MLL3 is carcinogenic in pancreatic and liver cancer, while it acts as a tumor suppressor in acute myeloid leukemia and esophageal squamous cell carcinoma. The effects of genes in tumors depend on certain environment and conditions, and the mechanism of the suppressive effect of MLL3 in leukemia is still not clear. This paper reviews the research progress of the antitumor mechanism of MLL3 in leukemia.

Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells / 中华医学杂志(英文版)

BACKGROUND@#Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated.@*METHODS@#The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry.@*RESULTS@#ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 .@*CONCLUSION@#ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.

Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and β-catenin / 中国针灸

OBJECTIVES@#To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients.@*METHODS@#Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups.@*RESULTS@#Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group.@*CONCLUSIONS@#In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.

Application of in vivo brain imaging technology in the basic research of acupuncture-moxibustion for encephalopathy / 中国针灸

Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.