Antitumor effects of Cypaliuruside F from Cyclocarya paliurus on HepG2 cells.

An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Macrophage-Capturing Self-Assembly Photosensitizer Nanoparticles Induces Immune Microenvironment Re-Programming and Golgi-Responsive Immunogenic Cell Death in Head and Neck Carcinoma.

Head and neck carcinoma treatment is shifted toward the combination of therapy causing immune checkpoint blockade (ICB) and immunogenic cell death. In this study, a CSFRi-chimeric TAMCSFR+-targeting extracellular vesicle (EV@CSFRi) platform is developed and designed an intracellular protoporphyrin conjugated with RVRR peptide sequence for furin-cleavage to perform Golgi-targeting and generating ROS (GT-RG). The graphical abstract illustrates the self-assembly of GT-RG nanoparticles into nanofiber through the hydrophily of RVRR and hydrophobicity of RG, and the red line indicates the site of furin cleavage. As is shown in the Graphical abstract, the Golgi-targeting Protoporphyrin-RVRR platform is composed with CSFRi-chimeric extracellular vesicles and forms the tumor-responsive TAM-reprogramming bilayers (GT-RGEV@CSFRi). The GT-RGEV@CSFRi acted as a multifunctional theranostic platform, which can induce immunogenic cell death and further help modulate TAM, thus suppressing the HNC xenograft model by combination therapy with anti-PD-1.

Nonextractable Polyphenols from Fu Brick Tea Alleviates Ulcerative Colitis by Controlling Colon Microbiota-Targeted Release to Inhibit Intestinal Inflammation in Mice.

This study was designed to elucidate the colon microbiota-targeted release of nonextractable bound polyphenols (NEPs) derived from Fu brick tea and to further identify the possible anti-inflammatory mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 1.5% DSS drinking water-induced C57BL/6J mice were fed rodent chow supplemented with or without 8% NEPs or dietary fibers (DFs) for 37 days. The bound p-hydroxybenzoic acid and quercetin in NEPs were liberated up to 590.5 ± 70.6 and 470.5 ± 51.6 mg/g by in vitro human gut microbiota-simulated fermentation, and released into the colon of the mice supplemented with NEPs by 4.4- and 1.5-fold higher than that of the mice supplemented without NEPs, respectively (p < 0.05). Supplementation with NEPs also enhanced the colonic microbiota-dependent production of SCFAs in vitro and in vivo (p < 0.05). Interestingly, Ingestion of NEPs in DSS-induced mice altered the gut microbiota composition, reflected by a dramatic increase in the relative abundance of Dubosiella and Enterorhabdus and a decrease in the relative abundance of Alistipes and Romboutsia (p < 0.05). Consumption of NEPs was demonstrated to be more effective in alleviating colonic inflammation and UC symptoms than DFs alone in DSS-treated mice (p < 0.05), in which the protective effects of NEPs against UC were highly correlated with the reconstruction of the gut microbiome, formation of SCFAs, and release of bound polyphenols. These findings suggest that NEPs as macromolecular carriers exhibit targeted delivery of bound polyphenols into the mouse colon to regulate gut microbiota and alleviate inflammation.

The influence of marital status at diagnosis on survival of adult patients with mantle cell lymphoma.

PURPOSE: Marital status has been reported to influence the survival outcomes of various cancers, but its impact on patients with mantle cell lymphoma (MCL) remains unclear. This study aimed to assess the influence of marital status at diagnosis on overall survival (OS) and cancer-specific survival (CSS) in patients with MCL. METHODS: The study utilized data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 databases, including 6437 eligible individuals diagnosed with MCL from 2000 to 2018. A 1:1 propensity matching method (PSM) minimized confounding factor. Univariate and multivariate analyses determined hazard ratios (HR). Stratified hazard models were developed for married and unmarried statuses across time intervals. RESULTS: Married patients exhibited better 5-year OS and CSS rates compared to unmarried patients (54.2% vs. 39.7%, log-rank p < 0.001; 62.6% vs. 49.3%, log-rank p < 0.001). Multivariate analysis indicated that being unmarried was an independent risk factor for OS (adjusted HR 1.420, 95% CI 1.329-1.517) and CSS (adjusted HR 1.388, 95% CI 1.286-1.498). After PSM, being unmarried remained an independent risk factor for both OS and CSS. Among unmarried patients, widowed individuals exhibited the poorest survival outcomes compared to patients with other marital statuses, with 5-year OS and CSS rates of 28.5% and 41.0%, respectively. Furthermore, in the 10-year OS and CSS hazard model for widowed individuals had a significantly higher risk of mortality, with the probability of overall and cancer-specific mortality increased by 1.7-fold and 1.6-fold, respectively. CONCLUSION: Marital status at diagnosis is an independent prognostic factor for MCL patients, with widowed individuals showing worse OS and CSS than those who are married, single, or divorced/separated. Adequate psychological and social support for widowed patients is crucial for improving outcomes in this patient population.

Discovery of a Novel Thienopyrimidine Compound as a Urate Transporter 1 and Glucose Transporter 9 Dual Inhibitor with Improved Efficacy and Favorable Druggability.

Gout and hyperuricemia are metabolic diseases characterized with high serum uric acid (SUA) levels that significantly impact human health. Lesinurad, a uricosuric agent, is limited to concurrent use with xanthine oxidase inhibitors (XOIs) in clinical practice due to its restricted efficacy and potential nephrotoxicity. Herein, extensive structural modifications of lesinurad were conducted through scaffold hopping and substituent modification strategies, affording 54 novel derivatives containing pyrimidine-fused cyclic structures. Notably, the thienopyrimidine compound 29 demonstrated a remarkable 2-fold increase in SUA-lowering in vivo activity compared to lesinurad, while exhibiting potent inhibitory activity against the urate transporter 1 (URAT1, IC50 = 2.01 µM) and glucose transporter 9 (GLUT9, IC50 = 18.21 µM). Furthermore, it possessed a lower effective dosage of 0.5 mg/kg, favorable safety profile without any apparent acute toxicity at doses of 1000 mg/kg, and improved pharmacokinetic properties. Overall, we have discovered an efficacious URAT1/GLUT9 dual inhibitor for inhibiting urate reabsorption with favorable pharmacokinetic profiles.

Exploring the mechanism of action of Shuangyang houbitong granules in the treatment of acute pharyngitis based on network pharmacology and molecular docking.

BACKGROUND: Acute pharyngitis (AP) refers to the acute inflammation of the pharynx, characterized by swelling and pain in the throat. Shuangyang houbitong granules (SHG), a traditional Chinese medicine compound, have been found to be effective in providing relief from symptoms associated with AP. METHODS: The chemical components of SHG were screened using Traditional Chinese Medicine Systems Pharmacology database, HERB database, and China National Knowledge Infrastructure. The targets of the granules were predicted using SwissTargetPrediction database. A network was constructed based on the targets of AP obtained from Genecards database, and protein-protein interaction analysis was performed on the intersection targets using STRING database. Key targets were screened for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and the binding activity of components and targets was predicted using AutoDockTools-1.5.7. RESULTS: A total of 65 components of SHG that met the screening criteria were retrieved, resulting in 867 corresponding targets. Additionally, 1086 AP target genes were retrieved, and 272 gene targets were obtained from the intersection as potential targets for SHG in the treatment of AP. Molecular docking results showed that the core components genkwanin, acacetin, apigenin, quercetin can stably bind to the core targets glyceraldehyde 3-phosphate dehydrogenase, interleukin 6, tumor necrosis factor, serine/threonine protein kinase, tumor protein 53, and epidermal growth factor receptor. CONCLUSION: The research results preliminarily predict and verify the mechanism of action of SHG in the treatment of AP, providing insights for further in-depth research.

Bioavailability and mechanisms of dietary polyphenols affected by non-thermal processing technology in fruits and vegetables.

Plant polyphenols play an essential role in human health. The bioactivity of polyphenols depends not only on their content but also on their bioavailability in food. The processing techniques, especially non-thermal processing, improve the retention and bioavailability of polyphenolic substances. However, there are limited studies summarizing the relationship between non-thermal processing, the bioavailability of polyphenols, and potential mechanisms. This review aims to summarize the effects of non-thermal processing techniques on the content and bioavailability of polyphenols in fruits and vegetables. Importantly, the disruption of cell walls and membranes, the inhibition of enzyme activities, free radical reactions, plant stress responses, and interactions of polyphenols with the food matrix caused by non-thermal processing are described. This study aims to enhance understanding of the significance of non-thermal processing technology in preserving the nutritional properties of dietary polyphenols in plant-based foods. It also offers theoretical support for the contribution of non-thermal processing technology in improving food nutrition.

Oleanolic acid alleviates obesity-induced skeletal muscle atrophy via the PI3K/Akt signaling pathway.

Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity-induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)-induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy.

Influence of oil extraction on concentration distributions, migration, secondary formation and carcinogenic risk of NPAHs and OPAHs in air and soil in an oilfield development area in China.

Oil extraction leads to environmental pollution from the oilfields and dweller activities, however, knowledge of the concentration distributions, migration, secondary formation and toxicity of nitrated/oxygenated polycyclic aromatic hydrocarbons (N/OPAHs) in oilfield regions is limited. In this research, atmospheric and soil samples in 7 different location types in an important oil industrial base in China were gathered. The ΣNPAHs and ΣOPAHs in the air ranged from 0.05 to 2.47 ng/m3 and 0.14-22.72 ng/m3, respectively, and in soil ranged from 0.22 to 17.81 ng/g and 9.69-66.86 ng/g, respectively. Both NPAHs and OPAHs in the atmosphere exhibited higher concentrations during winter. The atmospheric NPAH concentrations decreased exponentially with distance from urban area especially in the summer, revealing the impact of vehicles on the air in the Yellow River Delta area. High NPAH and OPAH concentrations were found only in soil near oil extraction facilities, indicating that the impact of oil extraction is limited to the soil near the extraction facilities. The air-soil exchanges of N/OPAHs were assessed through fugacity fraction analysis, and NPAHs were in the equilibrium-deposition state and OPAHs were in the net-deposition state in the winter. Higher incremental lifetime cancer risk (ILCR) occurred at the urban, industrial, and oilfield sites in the atmospheric samples, and the soil samples had the largest ILCR values in the oilfield sites. However, ILCR values for both air and soil did not exceed the threshold of 10-6.

Antioxidant Hydrogels: Antioxidant Mechanisms, Design Strategies, and Applications in the Treatment of Oxidative Stress-Related Diseases.

Oxidative stress is a biochemical process that disrupts the redox balance due to an excess of oxidized substances within the cell. Oxidative stress is closely associated with a multitude of diseases and health issues, including cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, inflammatory conditions, and aging. Therefore, the developing of antioxidant treatment strategies has emerged as a pivotal area of medical research. Hydrogels have garnered considerable attention due to their exceptional biocompatibility, adjustable physicochemical properties, and capabilities for drug delivery. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. In the pursuit of more effective treatments for oxidative stress-related diseases, there is an urgent need for advanced strategies for the fabrication of multifunctional antioxidant hydrogels. Consequently, the authors' focus will be on hydrogels that possess exceptional reactive oxygen species and reactive nitrogen species scavenging capabilities, and their role in oxidative stress therapy will be evaluated. Herein, the antioxidant mechanisms and the design strategies of antioxidant hydrogels and their applications in oxidative stress-related diseases are discussed systematically in order to provide critical insights for further advancements in the field.

Development of an analytic method for organosulfur compounds in Welsh onion and its use for nutritional quality analysis of five typical varieties in China.

A reliable, simple, and sensitive method capable of quantifying six organosulfur compounds (OSCs) was established. The samples were extracted by water containing 3 % formic acid with a simple vortex, ultrasound, and centrifugation step, and the solutions were analyzed by ultra-high-performance liquid chromatography separation system coupled with a triple-quadrupole mass spectrometry (UHPLC - MS/MS). Then the method was applied for the analysis of six OSCs in five varieties of two types Welsh onions in China, and the moisture content, reducing sugar, total polyphenols, and 21 free amino acids were also analyzed to study the characters of these Welsh onions intensively. Multivariate statistical analysis was used to investigate the differences in OSCs and free amino acids profiles among the samples. This study showed that enzymatic inhibition method combined with UHPLC - MS/MS is an effective technique to analyze OSCs in Welsh onion, and could be valuable for the routine quantitation of OSCs in other foods.

No consistent evidence for the anti-inflammatory effect of vagus nerve stimulation in humans: A systematic review and meta-analysis.

Vagus nerve stimulation (VNS) has been identified as an innovative immunosuppressive treatment strategy in rodent studies. However, its' clinical potential is still unclear. Therefore, we aimed to assess whether VNS can reduce inflammatory proteins and/or immune cells in humans, through a pre-registered systematic review and meta-analysis according to PRISMA guidelines. The databases Cochrane, Pubmed and World of Knowledge were searched in duplicate up to the 3rd of March 2022 and publications from identified clinical trial registrations were identified until 20th of August 2023. Studies were included if they provided peer-reviewed data for humans who received VNS as short-term (<=1 day) or long-term (>=2 days-365 days) stimulation and reported at least one cytokine or immune cell after treatment.Screening of title, abstract, full text, and data extraction was performed in duplicate by two independent reviewers. Data were pooled using a random-effects model and meta-regression was performed for moderating factors. Reporting bias was assessed. The standardized mean difference (Hedge's g) was used to indicate overall differences of cytokine data (mean and standard deviation or median and interquartile range at the study level) to test our a-priori hypothesis. The systematic review of 36 studies with 1135 participants (355 receiving a control/sham condition and 780 receiving VNS) revealed anti-inflammatory effects of VNS for cytokines in several reports, albeit often in subgroup analyses, but our meta-analyses of 26 studies did not confirm these findings. Although most cytokines were numerically reduced, the reduction did not reach statistical significance after VNS: not in the between-group comparisons (short-term: TNF-α: g = -0.21, p = 0.359; IL-6: g = -0.94, p = 0.112; long-term: TNF-α: g = -0.13, p = 0.196; IL-6: g = -0.67, p = 0.306); nor in the within-study designs (short-term: TNF-α: g = -0.45, p = 0.630; IL-6: g = 0.28, p = 0.840; TNF-α: g = -0.53, p = 0.297; IL-6:g = -0.02, p = 0.954). Only the subgroup analysis of 4 long-term studies with acute inflammation was significant: VNS decreased CRP significantly more than sham stimulation. Additional subgroup analyses including stimulation duration, stimulation method (invasive/non-invasive), immune stimulation, and study quality did not alter results. However, heterogeneity was high, and most studies had poor to fair quality. Given the low number of studies for each disease, a disease-specific analysis was not possible. In conclusion, while numeric effects were reported in individual studies, the current evidence does not substantiate the claim that VNS impacts inflammatory cytokines in humans. However, it may be beneficial during acute inflammatory events. To assess its full potential, high-quality studies and technological advances are required.

Gigantol protects retinal pigment epithelial cells against high glucose-induced apoptosis, oxidative stress and inflammation by inhibiting MTDH-mediated NF-kB signaling pathway.

OBJECTIVE: As a frequent complication of diabetes mellitus (DM), diabetic retinopathy (DR) is now one of the major causes of blindness. Recent reports have shown that retinal pigment epithelial cell (RPEC) damage plays an essential part in DR development and progression. This work intended to explore the potential effects of Gigantol on high glucose (HG)-stimulated RPEC damage and identify potential mechanisms. METHODS: Cell viability, cell damage, and cell apoptosis were evaluated by CCK-8, lactate dehydrogenase (LDH) and flow cytometry assays. The levels of oxidative stress biomarkers and pro-inflammatory cytokines were assessed using corresponding commercial kits and ELISA. Additionally, the levels of MTDH and NF-kB signaling pathway-related proteins were detected by western blotting. RESULTS: Gigantol dose-dependently enhanced cell viability and decreased apoptosis in HG-challenged ARPE-19 cells. Also, Gigantol notably relieved oxidative stress and inflammatory responses in ARPE-19 cells under HG conditions. Gigantol dose-dependently suppressed MTDH expression. In addition, MTDH restoration partially counteracted the protective effects of Gigantol on ARPE-19 cells subject to HG treatment. Mechanically, Gigantol inactivated the NF-kB signaling pathway, which was partly restored after MTDH overexpression. CONCLUSION: Our findings suggested that Gigantol protected against HG-induced RPEC damage by inactivating the NF-kB signaling via MTDH inhibition, offering a potent therapeutic drug for DR treatment.

Effect and mechanism of Banxia Xiexin decoction in colorectal cancer: A network pharmacology approach.

BACKGROUND: Banxia Xiexin decoction (BXD) is a traditional Chinese medicine with anti-colorectal cancer (CRC) activity. However, its bioactive constituents and its mechanism of action remain unclear. Herein, we explored the mechanism of action of BXD against CRC using a network pharmacology approach. METHODS: First, the targets of the main chemical components of BXD were predicted and collected through a database, and the intersection of compound targets and disease targets was obtained. Subsequently, protein-protein interaction network analysis, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the potential mechanisms underlying the effects of BXD on CRC. Finally, a CRC cell model and a CRC xenograft model in nude mice were utilized to further determine the mechanism of action. RESULTS: A compound-therapeutic target network of BXD was constructed, revealing 146 cellular targets of BXD. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling axis was identified as the main target of BXD. Using in vitro and in vivo models, the activity of BXD against CRC was found to be mediated through ferritinophagy by targeting the PI3K/AKT/mTOR axis, leading to intracellular iron accumulation, reactive oxygen species activation, and finally ferroptosis. CONCLUSIONS: Through the application of network pharmacology and in vitro/in vivo validation experiments, we discovered that BXD exerts anti-CRC effects via the ferritinophagy pathway. Furthermore, we elucidated the potential mechanism underlying its induction of ferritinophagy. These findings demonstrate the significant potential of traditional drugs in managing CRC and support their wider clinical application in combination chemotherapy, targeted therapy, and immunotherapy.

Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications.

Redox Regulation of Salt Tolerance in Eutrema salsugineum by Proteomics.

Salt stress severely restricts plant growth and crop production, which is accompanied by accumulation of reactive oxygen species (ROS) that disturb cell redox homeostasis and oxidize redox-sensitive proteins. Eutrema salsugineum, a halophytic species closely related to Arabidopsis, shows a high level of tolerance to salinity and is increasingly used as a model plant in abiotic stress biology. To understand redox modifications and signaling pathways under salt stress, we used tandem mass tag (TMT)-based proteomics to quantify the salt-induced changes in protein redox modifications in E. salsugineum. Salt stress led to increased oxidative modification levels of 159 cysteine sites in 107 proteins, which play roles in carbohydrate and energy metabolism, transport, ROS homeostasis, cellular structure modulation, and folding and assembly. These lists of unknown redox reactive proteins in salt mustard lay the foundation for future research to understand the molecular mechanism of plant salt response. However, glutathione peroxidase (GPX) is one of the most important antioxidant enzymes in plants. Our research indicates that EsGPX may be involved in regulating ROS levels and that plants with overexpressed EsGPX have much improved salt tolerance.

Research Advances in the High-Value Utilization of Peanut Meal Resources and Its Hydrolysates: A Review.

Peanut meal (PM) is a by-product of extracting oil from peanut kernels. Although peanut meal contains protein, carbohydrates, minerals, vitamins, and small amounts of polyphenols and fiber, it has long been used as a feed in the poultry and livestock industries due to its coarse texture and unpleasant taste. It is less commonly utilized in the food processing industry. In recent years, there has been an increasing amount of research conducted on the deep processing of by-products from oil crops, resulting in the high-value processing and utilization of by-products from various oil crops. These include peanut meal, which undergoes treatments such as enzymatic hydrolysis in industries like food, chemical, and aquaculture. The proteins, lipids, polyphenols, fibers, and other components present in these by-products and hydrolysates can be incorporated into products for further utilization. This review focuses on the research progress in various fields, such as the food processing, breeding, and industrial fields, regarding the high-value utilization of peanut meal and its hydrolysates. The aim is to provide valuable insights and strategies for maximizing the utilization of peanut meal resources.

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1-Non-Reactive Molecular Dynamics Simulations.

Plasma medicine, or the biomedical application of cold atmospheric plasma (CAP), is an expanding field within plasma research. CAP has demonstrated remarkable versatility in diverse biological applications, including cancer treatment, wound healing, microorganism inactivation, and skin disease therapy. However, the precise mechanisms underlying the effects of CAP remain incompletely understood. The therapeutic effects of CAP are largely attributed to the generation of reactive oxygen and nitrogen species (RONS), which play a crucial role in the biological responses induced by CAP. Specifically, RONS produced during CAP treatment have the ability to chemically modify cell membranes and membrane proteins, causing nitro-oxidative stress, thereby leading to changes in membrane permeability and disruption of cellular processes. To gain atomic-level insights into these interactions, non-reactive molecular dynamics (MD) simulations have emerged as a valuable tool. These simulations facilitate the examination of larger-scale system dynamics, including protein-protein and protein-membrane interactions. In this comprehensive review, we focus on the applications of non-reactive MD simulations in studying the effects of CAP on cellular components and interactions at the atomic level, providing a detailed overview of the potential of CAP in medicine. We also review the results of other MD studies that are not related to plasma medicine but explore the effects of nitro-oxidative stress on cellular components and are therefore important for a broader understanding of the underlying processes.

Molecular dynamics simulation of the transmembrane transport process of reactive species under the synergistic effect of plasma oxidation and an electric field.

Cold atmospheric pressure plasma (CAP)-assisted cancer therapy has become a popular topic in plasma biomedical research. Membrane lipid oxidation and local electric fields are two important factors in plasma-cell interactions, and the study of their synergistic effect is highly significant for optimizing the regulatory mechanism of the plasma-induced apoptosis of cancer cells. In this paper, a model of oxidized phospholipids was established, and the transmembrane process of reactive species was simulated by the classical molecular dynamics (MD) method under the conditions of oxidation and an electric field. The results showed that hydrophilic reactive oxygen species could not penetrate the membrane lipids through oxidation. The formation of electroporation provided a new channel for reactive species to penetrate the membrane, and the oxidation effect reduced the electric field threshold of membrane electroporation. Our simulation could provide theoretical support for the plasma-induced apoptosis of cancer cells at the microscopic level, provide mechanistic guidance for the practical application of plasma-induced cancer therapy, and promote the development of CAP in the field of cancer therapy.