Advances in anti-tumor mechanism and clinical application of Astragalus polysaccharides

Astragalus polysaccharide has the beneficial effect of Qi-deficiency,and it also has several anti-tumor mechanisms,including pharmacological actions and clinical functions.Through literature review,this work concluded anti-tumor mechanism and clinical application of astragalus polysaccharide,which was of considerable significance to expand and optimize its anti-tumor function and clinical application.

Study on the Anti-tumor Mechanism of Immunological Checkpoint Inhibitor PD-1

In recent years,the research of programmed death factor-1(PD-1)and its ligand(PD-L1)has made a great breakthrough in tumor therapy,and it is expected to change the clinical treatment manner of anti-tumor.In this paper,the role and mechanism of PD-1 inhibitors in anti-tumor are reviewed,thereby promoting their clinical application in anti-tumor immunotherapy.

Anti-tumor mechanism of Angelica and its compound preparations

Angelica is a holy medicine for gynecology, clinically used for blood deficiency and chlorosis, dizziness and palpitation, irregular menstruation, dysmenorrhea, abdominal pain, rheumatism, hemorrhoids, constipation. In recent years, with the discovery of polysaccharides enhancing the immune function and anti-tumor effects of the body, Angelica has attracted more and more attention from researchers at home and abroad.

The detailed anti-tumor mechanisms of daphnanetype diterpenoids from Genkwa flos

Genkwa flos is a well-known traditional Chinese medicine, which exhibits abundant biological activities such as antiinflammatory, analgesic, immunoregulatory activities and anti-rheumatic arthritis activity. Recent pharmacological studies showed that Genkwa flos might also have the antitumor effect. Daphnane-type diterpenoids (DDs) are one of the main anti-tumor constitutions in Genkwa flos. However, the underlying anticancer molecular mechanisms of this type of compounds are still unclear. This review aims to give a systematic summary of DDs from Genkwa flos to better understand the anti-tumor activitiy by focusing on cell arrest, apoptosis, topoisomerase inhibition, melanin inhibition and the reverse of multi-drug-resistance (MDR). In addition, we are also going to make an overview of the mechanisms identified up to now. The significant findings may provide that DDs in Genkwa flos is a promising targeted-cancer agent.

Advances in anti-tumor mechanisms of Venenum Bufonis

Venenum Bufonis is one of the traditional medical herbs,containing a variety of active ingredients such as peptides,alkaloids,lactones and sterols.In recent years,the significant anti-tumor effect of Venenum Bufonis and its active components,which are mainly composed of lipid scorpion venom,scorpion venom and scorpion venom,has become a research hotspot.Venenum Bufonis can inhibit the occurrence and development of tumor cells by inducing apoptosis of tumor cells,promoting tumor cell differentiation,inhibiting tumor microangiogenesis and reversing tumor cell resistance.Based on the chemical composition of Venenum Bufonis,this paper summarizes the mechanism of inhibiting tumors of the active ingredients in Venenum Bufonis.

Research Progress on Anti-tumor Mechanism of Clearing Heat-Toxin Intervention of Apoptosis-related Proteins

Apoptosis is a spontaneous programmed cell death process,which is closely related to the occurrence and development of tumors.Inducing apoptosis of tumor cells has become an important way of anti-tumor therapy.Studies have found that clearing heat-toxin Chinese medicine has a significant effect on inducing apoptosis,which may be the key mechanism of anti-tumor of Chinese medicine.By reviewing the theoretical origin of anti-tumor TCM of clearing heat-toxin Chinese herbs and the pharmacological research progress of intervening apoptosis-related proteins to promote apoptosis of tumor cells,this paper provides a basis for TCM to induce apoptosis of tumor cells to prevent and treat malignant tumors.

Study on Anti-tumor Mechanism of Poria cocos Based on Network Pharmacology

Background:This paper investigates the anti-tumor mechanism of action of Poria cocos on the basis of network pharmacology.Method:In this paper,we screen the potential active ingredients of Poria cocos by TCMSP and obtain their corresponding targets with SwissTargetPrediction.The GeneCards and OMIM databases are used to screen the relevant pathogenic candidate targets in various tumor disease processes.Furthermore,we obtain Poria cocos-tumor common targets by taking the intersection of Poria cocos potential targets and candidate target groups.Subsequently,the protein-protein interaction network(PPI)of common target genes is mapped based on the STRING database,and the"drug-active component-target gene-disease"network is constructed with the help of Cytoscape3.7.2.Therefore,the core target genes are obtained.Finally,GO and pathway enrichment analysis of the core target genes are performed by Metascape and DAVID.Results:38 common targets and 7 core genes(ESR1,MAPK3,MAPK8,MTOR,PIK3CA,JAK2,and IL6)in Poria cocos-tumors are found.They play an anti-tumor role by regulating various classical pathways such as PI3K-Akt signaling pathway,mTOR signaling pathway,Prolactin signaling pathway,ErbB signaling pathway,Choline metabolism in cancer.Conclusion:The research reveals the effective anti-tumor function of Poria as a multi-component,multi-target and multi-pathway herbal medicine.

Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Microdynamic mechanical properties and fracture evolution mechanism of monzogabbro with a true triaxial multilevel disturbance method

The far-field microdynamic disturbance caused by the excavation of deep mineral resources and underground engineering can induce surrounding rock damage in high-stress conditions and even lead to disasters.However,the mechanical properties and damage/fracture evolution mechanisms of deep rock induced by microdynamic disturbance under three-dimensional stress states are unclear.Therefore,a true triaxial multilevel disturbance test method is proposed,which can completely simulate natural geostress,excavation stress redistribution(such as stress unloading,concentration and rotation),and subsequently the microdynamic disturbance triggering damaged rock failure.Based on a dynamic true triaxial test platform,true triaxial microdynamic disturbance tests under different frequency and amplitudes were carried out on monzogabbro.The results show that increasing amplitude or decreasing frequency diminishes the failure strength of monzogabbro.Deformation modulus gradually decreases during disturbance failure.As frequency and amplitude increase,the degradation rate of deformation modulus decreases slightly,disturbance dissipated energy increases significantly,and disturbance deformation anisotropy strengthens obviously.A damage model has been proposed to quantitatively characterize the disturbance-induced damage evolution at different frequency and amplitude under true triaxial stress.Before disturbance failure,the micro-tensile crack mechanism is dominant,and the micro-shear crack mechanism increases significantly at failure.With the increase of amplitude and frequency,the micro-shear crack mechanism increases.When approaching disturbance failure,the acoustic emission fractal dimension changes from a stable value to local large oscillation,and finally increases sharply to a high value at failure.Finally,the disturbance-induced failure mechanism of surrounding rock in deep engineering is clearly elucidated.

Fabrication Techniques and Sensing Mechanisms of Textile‑Based Strain Sensors:From Spatial 1D and 2D Perspectives

The intelligent textile sensors based on fiber(1D)and fabric(2D)are the ideal candidates for wearable devices.Their flexible weaving and unique structure endow them with flexibility,lightweight,good air permeability,and feasible integration with garments.In view of the spring-up of novel textile-based strain sensors,the novel materials and fabrication approaches were elaborated from spatial perspectives,i.e.,1D fibers/yarn and 2D fabric.The intrinsic sensing mechanism is the primary fac-tor affecting sensor sensitivity,and the variation trend of the sensing signal is closely related to it.Although existing studies have involved various sensing mechanisms,there is still lacking systematic classification and discussion.Hence,the sensing mechanisms of textile-based sensors were elaborated from spatial perspectives.Considering that strain sensors were mostly based on resistance variation,the sensing mechanisms of resistive textile-based strain sensors were mainly focused,mainly including fiber deformation,tunneling effect,crack propagation,fabric deformation,electrical contact and bridge connec-tion.Meanwhile,the corresponding resistance prediction models,usually used as important data fitting methodology,were also comprehensively discussed,which can reproduce the resistance trend and provide guidance for the sensor performance.Finally,the multifunctionality of textile-based strain sensors was summarized,namely multi-mode signal detection,visual interaction,energy collection,thermal management and medical treatment were discussed.It was expected to provide research insights into the multifunctional integration of textile sensors.

Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect

The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.

Antagonism effect of residual S triggers the dual-path mechanism for water oxidation

Transition metal chalcogenides(TMCs)are recognized as pre-catalysts,and their(oxy)hydroxides derived from electrochemical reconstruction are the active species in the water oxidation.However,understanding the role of the residual chalcogen in the reconstructed layer is lacking in detail,and the corresponding catalytic mechanism remains controversial.Here,taking Cu_(1-x)Co_(x)S as a platform,we explore the regulating effect and existence form of the residual S doped into the reconstructive layer for oxygen evolution reaction(OER),where a dual-path OER mechanism is proposed.First-principles calculations and operando~(18)O isotopic labeling experiments jointly reveal that the residual S in the reconstructive layer of Cu_(1-x)Co_(x)S can wisely balance the adsorbate evolution mechanism(AEM)and lattice oxygen oxidation mechanism(LOM)by activating lattice oxygen and optimizing the adsorption/desorption behaviors at metal active sites,rather than change the reaction mechanism from AEM to LOM.Following such a dual-path OER mechanism,Cu_(0.4)Co_(0.6)S-derived Cu_(0.4)Co_(0.6)OSH not only overcomes the restriction of linear scaling relationship in AEM,but also avoids the structural collapse caused by lattice oxygen migration in LOM,so as to greatly reduce the OER potential and improved stability.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.