Research of the dynamic regulatory mechanism of Compound Danshen Dripping Pills on myocardial infarction based on metabolic trajectory analysis.

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PURPOSE: It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. METHODS: The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. RESULTS: CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. CONCLUSION: The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.

Optimal Ways of Safflower Oil Production with Improvement of Press Equipment.

This study aims to improve press equipment for safflower oil production by using a mechanism that optimizes pressure distribution within screw turns. A detailed analysis of the main components of the produced safflower oil was performed, encompassing both quantitative and qualitative assessments. Through the exploration of dependencies governing the safflower oil pressing process on the screw press, the optimal parameters were determined. As a result of the research, the optimal diaphragm gap between the gape cylinder and the pressing screw was determined, with the optimal oil yield percentage achieved at ω = 6.2 rad/s and δ = 5 mm. The study also compared the performance of the existing Dream Modern ODM-01 screw press and its upgraded version by analyzing the extracted oil. The results reveal changes in the quantitative and qualitative composition of the main oil components following the operation of the existing and the modernized screw presses. For instance, the amount of unsaturated fatty acids, such as oleic acid (7.7 ± 0.566%), linoleic acid (85.3 ± 1.185%), and linolenic acid (1.2 ± 0.223%), increased. There was an increase in the presence of inorganic substances in safflower oil: iron (0.023 ± 0.031 mg/kg), phosphorus (0.086 ± 0.059 mg/kg), silicium (0.136 ± 0.075 mg/kg), and others. The findings of this study hold significant commercial value and offer promising prospects for global market implementation.

Photoperiod and temperature synergistically regulate heading date and regional adaptation in rice.

Plants must accurately integrate external environmental signals with their own development to initiate flowering at the appropriate time for reproductive success. Photoperiod and temperature are key external signals that determine flowering time; both are cyclical and periodic and they are closely related to regulate flowering. In this review, we describe photoperiod-sensitive genes that simultaneously respond to temperature signals in rice (Oryza sativa). We introduce the mechanisms by which photoperiod and temperature synergistically regulate heading date and regional adaptation in rice. We also discuss the prospects for designing different combinations of heading date genes and other cold tolerance or thermo-tolerance genes to help rice better adapt to changes in light and temperature via molecular breeding to enhance yield in the future.

The Applications and Mechanisms of Superoxide Dismutase in Medicine, Food, and Cosmetics.

Superoxide dismutase (SOD) is a class of enzymes that restrict the biological oxidant cluster enzyme system in the body, which can effectively respond to cellular oxidative stress, lipid metabolism, inflammation, and oxidation. Published studies have shown that SOD enzymes (SODs) could maintain a dynamic balance between the production and scavenging of biological oxidants in the body and prevent the toxic effects of free radicals, and have been shown to be effective in anti-tumor, anti-radiation, and anti-aging studies. This research summarizes the types, biological functions, and regulatory mechanisms of SODs, as well as their applications in medicine, food production, and cosmetic production. SODs have proven to be a useful tool in fighting disease, and mimetics and conjugates that report SODs have been developed successively to improve the effectiveness of SODs. There are still obstacles to solving the membrane permeability of SODs and the persistence of enzyme action, which is still a hot spot and difficulty in mining the effect of SODs and promoting their application in the future.

GmDof41 regulated by the DREB1-type protein improves drought and salt tolerance by regulating the DREB2-type protein in soybean.

Despite their essential and multiple roles in biological processes, the molecular mechanism of Dof transcription factors (TFs) for responding to abiotic stresses is rarely reported in plants. We identified a soybean Dof gene GmDof41 which was involved in the responses to drought, salt, and exogenous ABA stresses. Overexpression of GmDof41 in soybean transgenic hairy roots attenuated H2O2 accumulation and regulated proline homeostasis, resulting in the drought and salt tolerance. Yeast one-hybrid and electrophoretic mobility shift assay (EMSA) illustrated that GmDof41 was regulated by the DREB1-type protein GmDREB1B;1 that could improve drought and salt tolerance in plants. Further studies illustrated GmDof41 can directly bind to the promoter of GmDREB2A which encodes a DREB2-type protein and affects abiotic stress tolerance in plants. Collectively, our results suggested that GmDof41 positively regulated drought and salt tolerance by correlating with GmDREB1B;1 and GmDREB2A. This study provides an important basis for further exploring the abiotic stress-tolerance mechanism of Dof TFs in soybean.

Salidroside Regulates the miRNA-1343-3p/MAP3K6/MMP24 Signaling Molecules to Inhibit Proliferation and Invasion of Gastric Cancer Cells / 中山大学学报(医学科学版)

ObjectiveThe aim of this study is to investigate the role of salidroside in regulating the miR-1343-3p/MAP3K6 （mitogen-activated protein kinase kinase kinase 6）/MMP24 （membrane-type matrix metalloproteinase 24） signaling pathway to inhibit gastric cancer cell proliferation and migration. MethodsHuman gastric cancer cells （MGC-803） were divided into several groups based on different salidroside concentrations： a control group （0 μmol/mL）， a low-dose group （6 μmol/mL）， a medium-dose group （12 μmol/mL）， and a high-dose group （24 μmol/mL）. The anti proliferative effects of salidroside on human gastric cancer cells were evaluated by CCK-8 assay. Clonogenic assay was used to examine the effects of salidroside drugs on the clonogenic ability of human gastric cancer cells. Transwell assay was performed to detect the effect of salidroside on the invasive ability of human gastric cancer cells. Cell scratch assay was performed to detect the effect of salidroside on the migration ability of human gastric cancer cells. The miRNA expression profile was analyzed by using RNA-seq in cancer cells for 24 h after salidroside treatment. The differentially expressed miRNAs were clustered and their target genes were predicted. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） were used to analyze and predict the functions of these target genes， and the interaction networks were established. Immunocytofluorescence was used to detect the expression of target proteins， and the transcription of candidate genes was detected by q-PCR. ResultsCCK-8 cytotoxicity experiments showed that salidroside inhibited the proliferation of MGC-803 cells （P < 0.01）. Cell cloning experiments showed that salidroside reduced the clonal formation capacity of MGC-803 cells （P < 0.000 1）. Cell invasion experiments showed that salidroside reduced the MGC-803 cell invasion capacity （P < 0.000 1）. Cell scratch experiments showed that salidroside reduced the cell migration capacity （P < 0.000 1）. RNA-seq findings showed that the expression of 44 miRNAs changed significantly after salidroside treatment in cancer cells （P < 0.05）. Bioinformatic analysis showed that there were 1 384 target mRNAs corresponding to the differentially expressed miRNAs， and the expression of the tumor suppressor miR-1343-3p was significantly upregulated after salidroside treatment （P < 0.01），and resulted in down-regulated transcription of MAP3K6 and MMP24 genes which are related to the proliferation and migration of cancer cells （P < 0.05）. Immunofluorescence experiments demonstrated that salidroside reduced protein expression levels in MAP3K6 and MMP24 genes （P < 0.000 1）. q-PCR experiments showed that salidroside reduced the mRNA expression level of MAP3K6 and MMP24 genes （P < 0.000 1）， while miRNA expression in miR-1343-3p gene was upregulated （P < 0.000 1）. ConclusionSalidroside regulates the miRNA-1343-3p/MAP3K6/MMP24 signaling molecules to inhibit proliferation and invasion of gastric cancer cells.

Both Two CtACO3 Transcripts Promoting the Accumulation of the Flavonoid Profiles in Overexpressed Transgenic Safflower.

The unique flavonoids, quinochalcones, such as hydroxysafflor yellow A (HSYA) and carthamin, in the floret of safflower showed an excellent pharmacological effect in treating cardiocerebral vascular disease, yet the regulating mechanisms governing the flavonoid biosynthesis are largely unknown. In this study, CtACO3, the key enzyme genes required for the ethylene signaling pathway, were found positively related to the flavonoid biosynthesis at different floret development periods in safflower and has two CtACO3 transcripts, CtACO3-1 and CtACO3-2, and the latter was a splice variant of CtACO3 that lacked 5' coding sequences. The functions and underlying probable mechanisms of the two transcripts have been explored. The quantitative PCR data showed that CtACO3-1 and CtACO3-2 were predominantly expressed in the floret and increased with floret development. Subcellular localization results indicated that CtACO3-1 was localized in the cytoplasm, whereas CtACO3-2 was localized in the cytoplasm and nucleus. Furthermore, the overexpression of CtACO3-1 or CtACO3-2 in transgenic safflower lines significantly increased the accumulation of quinochalcones and flavonols. The expression of the flavonoid pathway genes showed an upward trend, with CtCHS1, CtF3H1, CtFLS1, and CtDFR1 was considerably induced in the overexpression of CtACO3-1 or CtACO3-2 lines. An interesting phenomenon for CtACO3-2 protein suppressing the transcription of CtACO3-1 might be related to the nucleus location of CtACO3-2. Yeast two-hybrid (Y2H), glutathione S-transferase (GST) pull-down, and BiFC experiments revealed that CtACO3-2 interacted with CtCSN5a. In addition, the interactions between CtCSN5a and CtCOI1, CtCOI1 and CtJAZ1, CtJAZ1 and CtbHLH3 were observed by Y2H and GST pull-down methods, respectively. The above results suggested that the CtACO3-2 promoting flavonoid accumulation might be attributed to the transcriptional activation of flavonoid biosynthesis genes by CtbHLH3, whereas the CtbHLH3 might be regulated through CtCSN5-CtCOI1-CtJAZ1 signal molecules. Our study provided a novel insight of CtACO3 affected the flavonoid biosynthesis in safflower.

Exploring the regulating mechanism of heat induced gelation of myosin by binding with Mb hemin prosthetic group.

The properties, structure and water holding capacity of myosin were analyzed after incubated with myoglobin (Mb) hemin prosthetic group. The results revealed moderate oxidation of hemin prosthetic group could improve the solubility of myosin. Besides, it could stretch the protein structure and cross-link the molecules to form the soluble polymer. Hence, moderate oxidation could improve the gel properties and the gel network structure. However, excessive oxidation would greatly reduce the physical and chemical properties of myosin, which was not conducive to the gel formation and would lead to a decrease in water retention. Moreover, fluorescence spectroscopy and cyclic voltammetry (CV) proved hemin prosthetic group had a high affinity for myosin. The interaction mechanism was further studied by molecular docking and molecular dynamics (MD) simulations. This study provides some fundamental prospects to be applied in the functional regulation of meat protein.

Bisphenol A biodegradation by Sphingonomas sp. YK5 is regulated by acyl-homoserine lactone signaling molecules.

Microbial degradation is an effective approach for the removal of Bisphenol A (BPA). During the biodegradation process, quorum sensing (QS) is a phenomenon that enables bacteria to coordinate collective behaviors based on cell density-dependent chemical signals. However, whether the degradation of BPA can be facilitated by this QS system (such as acyl-homoserine lactone, AHL) is unclear. To answer this question, the bifunctional Sphingonomas sp. strain YK5 that had BPA-degrading and AHL-producing properties was used. Biochemical analysis revealed that this bacterial strain mainly produced C8-HSL signals. Gene knockout experiments indicated that the AHL-system (LuxI1/LuxI2) was required for efficient BPA degradation. RT-PCR analyses revealed that the AHL system positively regulated the relative expression of genes (bisdA, CYP450, hapA, ligAB, and proB) involved in BPA degradation. Given that AHL signaling may be a common trait among BPA-degrading microorganisms and AHL system can regulate the degradation activity, manipulation of this system may be a valuable strategy to control BPA biodegradation.

Lung cancer and epithelial-mesenchymal transition.

Lung cancer (LC) is a leading cause of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) is a well-known phenomenon that promotes the invasive and metastatic capabilities of LC. Especially, EMT is assumed to be a pivotal mechanism for tumor cell invasion and metastasis, thereby limiting the efficacy of surgery and medical treatments, resulting in poor patient prognoses. Thus, the elucidation and reversal of EMT could provide changes in therapeutic strategies for LC. To overcome the limitations of currents treatment regimens for LC, it is important for surgeons to be familiar with this complex tumor characteristic. In this review, the activating signaling pathways underlying EMT and the associated tumor phenotypes are briefly described.

Trauma during humanitarian work: the effects on intimacy, wellbeing and PTSD-symptoms.

Background: Organizations assisting refugees are over burdened with the Syrian humanitarian catastrophe and encounter diverse difficulties facing the consequences of this massive displacement. Aid-workers experience the horrors of war through their efforts to alleviate suffering of Syrian refugees. Objective: This study of Syrian refugee aid-workers in Jordan examined work-stressors identified as secondary traumatic stress (STS), number of refugees assisted, worker feelings towards the organization, and their associations to PTSD-symptoms, wellbeing and intimacy. It also examined whether self-differentiation, physical health, and physical pain were associated with these variables. Method: Syrian refugee aid-workers (N = 317) in Jordan's NGOs were surveyed. Univariate statistics and structural equation modeling (SEM) were utilized to test study hypotheses. Results: Increased STS was associated with lower self-differentiation, decreased physical health and increased physical pain, as well as elevated PTSD-symptoms and decreased intimacy. Decreased connection to the NGO was associated with lower self-differentiation, decreased physical health, increased physical pain, and with decreased intimacy and wellbeing. Lower self-differentiation was associated with increased PTSD-symptoms, decreased wellbeing and intimacy. Elevated physical pain was associated with increased PTSD-symptoms, and decreased wellbeing. Diverse mediation effects of physical health, physical pain and self-differentiation were found among the study's variables. Conclusions: Aid-workers who assist refugees were at risk of physical and mental sequelae as well as suffering from degraded self-differentiation, intimacy and wellbeing. Organizations need to develop prevention policies and tailor interventions to better support their aid-workers while operating in such stressful fieldwork.

Antecedentes: Las organizaciones que ayudan a los refugiados están sobrecargadas con la ayuda humanitaria siria catástrofe y encontrar diversas dificultades que enfrentan las consecuencias de esta masiva. Los trabajadores de ayuda al desplazamiento experimentan los horrores de la guerra a través de sus esfuerzos para alivian el sufrimiento de los refugiados sirios.Objetivo: Este estudio de trabajadores humanitarios de refugiados sirios en Jordania examinó los estresores laborales identificados como el estrés traumático secundario (STS en sus siglas en inglés), el número de refugiados asistidos, los sentimientos del trabajador con respecto a la organización, y sus asociaciones con los síntomas del TEPT, bienestar e intimidad. Se examinó también si la auto-diferenciación, la salud física, y el dolor físico se asociaban con estas variables.Método: Se encuestaron los trabajadores humanitarios de refugiados sirios (N=317) de organizaciones no gubernamentales (ONGs) en Jordania. Se utilizaron las estadísticas univariadas y el modelamiento de ecuaciones estructurales (SEM en sus siglas en inglés) para probar las hipótesis del estudio.Resultados: El aumento en el STS se asoció con una más baja auto-diferenciación, una disminuida salud física y un aumento del dolor físico, como también con síntomas elevados de TEPT y una intimidad disminuida. Una conexión disminuida con la ONG se asoció con una más baja auto-diferenciación, una disminuida salud física, un aumento de dolor físico, y con una disminuida intimidad y bienestar. Una más baja auto-diferenciación se asoció con un aumento en los síntomas del TEPT, y un disminuido bienestar e intimidad. El dolor físico elevado fue asociado con un aumento en los síntomas del TEPT, y un disminuido bienestar. Se encontraron diversos efectos mediadores de la salud física, dolor físico y la auto-diferenciación entre las variables del estudio.Conclusiones: Los trabajadores humanitarios que asisten a los refugiados se encuentran en riesgo de secuelas físicas y mentales como también de sufrir un deterioro en su auto-diferenciación, intimidad y bienestar. Las organizaciones necesitan desarrollar políticas de prevención y adaptar intervenciones para apoyar mejor a sus trabajadores humanitarios mientras operan en tan estresante campo laboral.

Protective effects of heparin on endothelial cells in sepsis.

OBJECTIVE: This study aims to observe the protective effects of heparin on endothelial cells in sepsis and explore the involved signal pathway regulated by heparin. Methods Human vascular endothelial cells were treated by TNFα in vitro to simulate the inflammatory environment when sepsis occurred. They were intervened by heparin and the expression levels of soluble thrombomodulin (sTM) and serum activated protein C (APC) were detected by ELISA, the regulatory mechanism of heparin improving vascular endothelial cells injury induced by TNFα was detected by Western Blotting method, the methylation of histone in the gene promoter region of endothelial nitric oxide synthase (eNOS) and monocyte chemotactic protein-1 (MCP-1) were detected using chromatin immunoprecipitation method. Results Heparin could inhibit the secretion of sTM and APC protein and the expression of MCP-1 gene which involved in NF-κB signal pathway. Conclusions Heparin could protect vascular endothelial cells from injury induced by TNFα and sepsis, the mechanisms were related with the effects of heparin on the histone methylation of promoter region and the regulation of heparin on the MAPK and NF-κB signal pathways. These results provide a theoretical basis for the application of heparin in the prevention and treatment of vascular disease related with sepsis.

Long-term Weight Loss Maintenance

It is not easy to maintain long-term weight loss even though it is the ultimate goal of obesity management. The Look AHEAD study in which 50% of participants in the intervention arm maintained a weight loss at least 5% below their initial weight after 8 years of intensive lifestyle intervention confirms a crucial role of continuous and constant application of lifestyle changes. Alteration of appetite-related hormones, energy homeostasis, nutrient metabolism, and subjective appetite are involved in biological pathways responsible for balance between energy utilization and storage following weight loss. Previous studies have shown that some appetite-related hormones and metabolites are potential predictors of weight-regain after weight loss, and specific diet pattern and physical activity could oppose weight loss regain.

Mechanism of tumor angiogenesis / 国际肿瘤学杂志

Based on the theory of tumor angiogenesis,the vascular system is necessary for the advance and metastasis of the tumor.To inhibit or even cure the tumor,the researchers all over the world have made a great many of studies on the mechanism of tumor angiogenesis and have acquired some achievements.Based on the findings,a lot of factors are involved in tumor angiogenesis,and they constitute the complex regulating network through interaction at the molecular and cellular level.