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BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.
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Neoplasias Ósseas , Naftoquinonas , Osteossarcoma , Humanos , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2 , Apoptose , Osteossarcoma/patologia , Linhagem Celular Tumoral , Neoplasias Ósseas/metabolismo , Proliferação de Células , Proteína 1 de Resposta de Crescimento Precoce/farmacologiaRESUMO
Dietary nutritional support for special populations is an effective and feasible method to improve the quality of life of patients and reduce medical pressure. Acer truncatum Bunge seed oil (ATSO) is widely recognized for its ability to promote nerve myelin regeneration. To evaluate the ameliorative effects of ATSO on chemotherapy-induced demyelination, a zebrafish model of chemotherapy-induced demyelination was established. The results showed that 100 µg mL-1 of ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, and pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, and nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components improving mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.
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Acer , Antineoplásicos , Doenças Desmielinizantes , Doenças Mitocondriais , Animais , Humanos , Mitofagia , Oxaliplatina/farmacologia , Peixe-Zebra/metabolismo , Qualidade de Vida , Sementes/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Óleos de Plantas/farmacologia , Antineoplásicos/farmacologia , Proteínas Serina-Treonina QuinasesRESUMO
Magnetic two-dimensional nanocomposites (M2D NCs) that synergistically combine magnetic nanomedicine and 2D nanomaterials have emerged in multimodal antitumor therapy, attracting great interest in materials science and biomedical engineering. This review provides a summary of the recent advances of M2D NCs and their multimodal antitumor applications. We first introduce the design and fabrication of M2D NCs, followed by discussing new types of M2D NCs that have been recently reported. Then, a detailed analysis and discussions about the different types of M2D NCs are presented based on the structural categories of 2D NMs, including 2D graphene, transition metal dichalcogenides (TMDs), transition metal carbides/nitrides/carbonitrides (MXenes), black phosphorus (BP), layered double hydroxides (LDHs), metal organic frameworks (MOFs), covalent organic frameworks (COFs) and other 2D nanomaterials. In particular, we focus on the synthesis strategies, magnetic or optical responsive performance, and the versatile antitumor applications, which include magnetic hyperthermia therapy (MHT), photothermal therapy (PTT), photodynamic therapy (PDT), drug delivery, immunotherapy and multimodal imaging. We conclude the review by proposing future developments with an emphasis on the mass production and biodegradation mechanism of the M2D NCs. This work is expected to provide a comprehensive overview to researchers and engineers who are interested in such a research field and promote the clinical translation of M2D NCs in practical applications.
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Hipertermia Induzida , Nanocompostos , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Nanocompostos/química , Fenômenos MagnéticosRESUMO
Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and mechanical pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model. Second, we identified higenamine as a major component of asarum and found that higenamine significantly inhibited thermal and mechanical induced acute pain and CFA induced chronic inflammatory pain. Then, using Trpv4-/- mice, we found that TRPV4 is necessary for CFA induced thermal and mechanical allodynia, and demonstrated that higenamine analgesia in the CFA model is partly through TRPV4 channel inhibition. Finally, we found that GSK1016790A, a TRPV4 agonist, induced calcium response was significantly inhibited by higenamine in both cultured DRG neurons and TRPV4 transfected HEK293 cells. Consistent with calcium imaging results, higenamine pretreatment also dose-dependently inhibited GSK1016790A induced acute pain. Taken together, our behavior and calcium imaging results demonstrate that the asarum component higenamine inhibits acute and chronic inflammatory pain by modulation of TRPV4 channels.
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Alcaloides , Dor Crônica , Canais de Cátion TRPV , Tetra-Hidroisoquinolinas , Animais , Humanos , Camundongos , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Cálcio/metabolismo , Dor Crônica/tratamento farmacológico , Células HEK293 , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Leucina/análogos & derivados , Sulfonamidas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidoresRESUMO
Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".
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Saunas are becoming increasingly popular worldwide, being an activity that promotes relaxation and health. Intense feelings of happiness have been reported shortly after enjoying a hot sauna and cold water, what is known in Japan as the "totonou" state. However, no research has investigated what occurs in the brain during the "totonou" state. In the present study, participants underwent a sauna phase, consisting of three sets of alternating hot sauna, cold water, and rest. We elucidated changes in brain activity and mood in the "totonou" state by measuring and comparing brain activity and emotional scales before and after the sauna phase and during the rest phase in each set. We found significant increases in theta and alpha power during rest and after the sauna phase compared to before the sauna phase. Moreover, in an auditory oddball task, the p300 amplitude decreased significantly and MMN amplitude increased significantly after the sauna phase. The increase in MMN indicates higher activation of the pre-attentional auditory process, leading to a decrease in attention-related brain activity P300. Hence, the brain reaches in a more efficient state. Further, the response time in behavioral tasks decreased significantly. In addition, the participants' subjective responses to the questionnaire showed significant changes in physical relaxation and other indicators after being in the sauna. Finally, we developed an artificial intelligence classifier, obtaining an average accuracy of brain state classification of 88.34%. The results have potential for future application.
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Banho a Vapor , Humanos , Inteligência Artificial , Banhos , Encéfalo , ÁguaRESUMO
CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ratos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gencitabina , Citocromo P-450 CYP3A , Regulação para Baixo , Ratos Sprague-Dawley , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
PURPOSE: Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. METHODS: This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. RESULTS: A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. CONCLUSION: Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives.
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Raquianestesia , Musicoterapia , Música , Ressecção Transuretral da Próstata , Masculino , Idoso , Humanos , Pessoa de Meia-Idade , Raquianestesia/efeitos adversos , Estudos Prospectivos , Hipnóticos e SedativosRESUMO
This study investigates the interaction between montmorillonite and polyacrylamide (PAM) with different ionic types using quartz crystal microbalance with dissipation monitoring (QCM-D) and molecular dynamics (MD) simulations. The goal was to understand the effect of ionicity and ionic type on polymer deposition on montmorillonite surfaces. The results of the QCM-D analysis showed that a decrease in pH led to an increase in the adsorption of montmorillonite on the alumina surface. The ranking of adsorption mass on alumina and pre-adsorbed montmorillonite alumina surfaces was found to be cationic polyacrylamide (CPAM) > polyacrylamide (NPAM) > anionic polyacrylamide (APAM). The study also found that CPAM had the strongest bridging effect on montmorillonite nanoparticles, followed by NPAM, while APAM had a negligible bridging effect. The MD simulations showed that ionicity had a significant influence on the adsorption of polyacrylamides. The cationic functional group N(CH3)3+ had the strongest attraction interaction with the montmorillonite surface, followed by the hydrogen bonding interaction of the amide functional group CONH2, and the anionic functional group COO- had a repulsive interaction. The results suggest that at high ionicity levels, CPAM can be adsorbed on the montmorillonite surface, while at low ionicity levels, APAM may still be adsorbed with a strong coordination trend.
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Bentonita , Técnicas de Microbalança de Cristal de Quartzo , Adsorção , Técnicas de Microbalança de Cristal de Quartzo/métodos , Simulação de Dinâmica Molecular , Íons , Óxido de Alumínio , Propriedades de SuperfícieRESUMO
BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.
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Sobreviventes de Câncer , Carcinoma Neuroendócrino , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Estudos de Coortes , Recidiva Local de Neoplasia , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologiaRESUMO
Sarcopenia is a syndrome of age-related loss of muscle mass and strength that seriously affects human health, and there are currently no effective drugs to treat the disease. Linolenic acid as a common n-3 polyunsaturated fatty acid (n-3 PUFA) is known to have many beneficial functions. Some studies have found that n-3 PUFA might have the potential to improve sarcopenia. In this study, Caenorhabditis elegans (C. elegans) was used as a model animal to investigate the effects of linolenic acid on C. elegans muscles. The results showed that 50 µg mL-1 linolenic acid significantly improved sarcopenia by repairing mitochondrial function by promoting mitophagy and fighting oxidative stress (p < 0.05). This included the increase of the expression of the mitophagy gene pink-1 and DAF-16/FOXO transcription factors, respectively, by linolenic acid. This study could provide some evidence for the application of n-3 PUFA in improving sarcopenia.
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Proteínas de Caenorhabditis elegans , Ácidos Graxos Ômega-3 , Sarcopenia , Animais , Humanos , Caenorhabditis elegans/genética , Sarcopenia/tratamento farmacológico , Sarcopenia/metabolismo , Ácido alfa-Linolênico/farmacologia , Ácido alfa-Linolênico/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mitofagia , Estresse Oxidativo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Fatores de Transcrição Forkhead/metabolismo , LongevidadeRESUMO
Although data indicate omega-3 polyunsaturated fatty acids are beneficial nutrients in cancer therapy, the evidences for efficacy of nutritional interventions during chemo (radio) therapy are still limited. The leading goal of the present meta-analysis was to summarize randomized controlled trials involving the administration of ω-3 PUFA-enriched oral nutritional supplements during chemo (radio) therapy, and evaluate the effects on nutritional status and clinical outcomes in patients. We systematically searched PubMed, Embase, Web of Science, Cochrane databases to identify interventions assessing body weight, BMI, immune and inflammatory indicators, plasma omega-3 fatty acids and adverse events, with subgroup analyses for region, types of ω-3 fatty acids, dose, duration and dosage form. In total, 22 studies including 1155 participants met the inclusion criteria. Meta-analysis showed a significant increase in body weight (BW) (WMD = 0.59 kg, 95% CI: 0.06, 1.13, P = 0.03), body mass index (BMI) (WMD = 0.43 kg/m2, 95% CI: 0.07, 0.79, P = 0.02), and plasma total ω-3 fatty acids (SMD = 2.52, 95% CI: 1.27, 3.78, P<0.0001), and a significant reduction in plasma levels of C-reactive protein (CRP) (SMD= -0.53, 95% CI: -0.80, -0.25, P = 0.0001), tumor necrosis factor-α (TNF-α) (WMD = -0.40 pg/mL, 95% CI: -0.80, -0.01, P = 0.05), interleukin 6 (IL-6) (WMD = -1.25 pg/mL, 95% CI: -2.41, -0.10, P = 0.03) and the incidence of adverse events (RR= 0.72, 95% CI: 0.54, 0.95, P = 0.02). However, plasma albumin levels (WMD = 0.02 mg/dL, 95% CI: -0.13, 0.18, P = 0.75) was remained unaffected. Overall, our meta-analysis provides evidences that the consumption of ω-3 PUFA-enriched oral nutritional supplements exert beneficial effects on nutritional status and clinical outcomes in patients undergoing chemo (radio) therapy.
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Ácidos Graxos Ômega-3 , Neoplasias , Humanos , Suplementos Nutricionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Peso Corporal , Neoplasias/tratamento farmacológicoRESUMO
With the rapid development of the international community, foreign language learning has become increasingly important. Listening training is a particularly important component of foreign language learning. The most difficult aspect of listening training is the development of speech discrimination ability, which is crucial to speech perception. General behavioral training requires a substantial amount of time and attention. To address this, we previously developed a neurofeedback (NF) training system that enables unconscious learning of auditory discrimination. However, to our knowledge, no studies have compared NF training and general behavioral training. In the present study, we compared the learning effects of NF training, general behavioral training, and a combination of both strategies. Specifically, we developed a gamified and adapted NF training of auditory discrimination. We found that both NF training and general behavioral training enhanced behavioral performance, whereas only NF training elicited significant changes in brain activity. Furthermore, the participants that used both training methods exhibited the largest improvement in behavioral performance. This indicates that the combined use of NF and general behavioral training methods may be optimal for enhancing auditory discrimination ability when learning foreign languages.
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Neurorretroalimentação , Percepção da Fala , Humanos , Aprendizagem , Percepção Auditiva , Discriminação PsicológicaRESUMO
Purpose: This study focused on determining the anticancer effect of paeoniflorin and geniposide mixture (PFGS) combined with sorafenib (Sor) in hepatocellular carcinoma (HCC) and, in particular, whether PFGS increases the antitumor effect of Sor by modulating the NF-κB/HIF-2α/SerpinB3 pathway. Methods: The H22 hepatoma tumor-bearing mouse model was treated with PFGS, Sor, and a combination of the two drugs for 12 days. The effects of PFGS combined with Sor on tumor growth and apoptosis and the expression of NF-κB, HIF-2α, and SerpinB3 in tumor tissue were assessed. In addition, Sor-resistant hepatoma cells were treated with PFGS, Sor, and the combination of the two drugs in vitro. The effects of PFGS combined with Sor on cell proliferation and invasion and the protein expression of NF-κB p65, HIF-2α, and SerpinB3 were investigated. Results: PFGS combined with Sor treatment synergistically inhibited tumor growth in HCC tumor-bearing mice. Immunostaining showed that PFGS combined with Sor treatment significantly decreased the expression of Ki-67 and obviously induced apoptosis in the tumor compared with a single treatment. Similarly, PFGS combined with Sor treatment significantly downregulated the expression of NF-κB, HIF-2α, and SerpinB3 in the tumor compared with a single treatment. Additionally, PFGS combined with Sor markedly inhibited cell proliferation and invasion and activation of the NF-κB/HIF-2α/SerpinB3 pathway in Sor-resistant hepatoma cells compared with a single treatment. Conclusion: Our study demonstrated that PFGS synergistically increased the antiliver cancer effects of Sor by lowering activation of the NF-κB/HIF-2α/SerpinB3 pathway. These findings provided a scientific foundation for clinical studies using PFGS and Sor to treat liver cancer.
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Owing to having a unique mechanism to kill cancer cells via the membrane accumulation of lipid peroxide (LPO) and the downregulation of glutathione peroxidase-4 (GPX-4), the ferroptosis therapy (FT) of tumors based on the Fenton reaction of iron nanoparticles has been receiving much attention in the past decade; however, there are some hurdles including the uncontrollable release of iron ions, slower kinetics of the intracellular Fenton reaction, and poor efficacy of FT that need to be overcome. Considering cooperative coordination of a multivalent thiol-pendant polypeptide ligand with iron ions, we put forward a facile strategy for constructing the iron-coordinated nanohybrid of methacryloyloxyethyl phosphorylcholine-grafted polycysteine/iron ions/tannic acid (i.e., PCFT), which could deliver a higher concentration of iron ions into cells. The dynamic and unsaturated coordination in PCFT is favorable for the intracellular stimuli-triggered release and fast Fenton reaction to realize efficient FT, while its intrinsic photothermia would boost the Fenton reaction to induce a synergistic effect between FT and photothermal therapy (PTT). Both immunofluorescence analyses of reactive oxygen species (ROS) and LPO confirmed that the intracellular Fenton reaction resulted in efficient FT, during which process the photothermia greatly boosted ferroptosis, and the Western blot assay corroborated that the expression level of GPX-4 was downregulated by FT and highly degraded by the photothermia to induce synergistic PTT-FT in vitro. Excitingly, by a single intravenous dose of PCFT plus one NIR irradiation, in vivo PTT-FT treatment completely eradicated 4T1 tumors without skin scar and tumor recurrence for 16 days, demonstrating prominent antitumor efficacy, as evidenced by the GPX-4, H&E, and TUNEL assays.
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Ferroptose , Hipertermia Induzida , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Ferro , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Peptídeos/uso terapêutico , Terapia Fototérmica , TaninosRESUMO
With the progress in the study of functional lipid, interest has turned recently to the medium- and long-chain triglyceride (MLCT) obtained by modification of natural oil. From a health perspective, MLCT not only provides us with the essential fatty acids, but,moreimportantly,it also reduces body fat accumulation, improves insulin resistance and plays an important role in clinical nutritional treatment. The potential effectiveness of MLCT in the human body is influenced mainly byits digestion and absorption in thegastrointestinaltract. However, the current understanding of the digestion and absorption mechanism of MLCT is still not comprehensive. Thisreview first presents the nutritional properties, digestion and absorption of MLCT. Then it will focus on the effects of MLCT compositions and structures (eg, fatty acid chain length, saturation, and location distribution) on its digestion and absorption process for a better understanding of its nutritional properties. This review also presents the synthesis methods and current application status of MLCT. Finally, the advantages, challenges and future prospects of MLCT are discussed. With its potential health benefits, MLCT is widely being used as nutraceutical in food and pharmaceutical sectors. In the future, the purpose of modifying the digestion and absorption of MLCT can be realized by structural design and other means, to achieve nutritional supplement and precise therapy.
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Tecido Adiposo , Ácidos Graxos , Digestão , Ácidos Graxos/química , Humanos , Triglicerídeos/químicaRESUMO
Liposoluble antioxidants, including natural and synthetic antioxidants, are substances to prevent lipid oxidation. From previous studies, the interaction of antioxidants may be the main reason for the poor correlation between liposoluble phytochemicals and antioxidant activity in oils. This review brings together information concerning the types and mechanisms of antioxidant interactions in terms of structure and active groups. A critical summary of the interactions between liposoluble antioxidants (synergistic effects, antagonistic effects and additive effects) is given. Factors including the diverse structure, combinations with different concentrations or proportions, and the reaction system which affect the interactions between liposoluble antioxidants, along with the opportunities and challenges in future study are also discussed. However, the influencing factors and mechanism still require further investigation. It is proposed that the studies in whole foods system and in vivo along with the related interaction mechanism should be considered in future.
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Antioxidantes , Compostos Fitoquímicos , Antioxidantes/química , Alimentos , Extratos Vegetais/química , Óleos de PlantasRESUMO
Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1® (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Müller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.
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Cordyceps , Animais , Carotenoides/metabolismo , Carotenoides/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Água/metabolismoRESUMO
Non-alcoholic fatty liver disease (NAFLD) can be attributed to the imbalance between lipogenesis and lipidolysis in the liver. Sesame lignans (sesamin, sesamolin, and sesamol) are unique bioactive compounds responsible for the nutritional function of sesame oils. However, the preventive effects of three lignans on oxidative stress and lipid metabolism in steatosis HepG2 cells have not been compared. In this study, we investigated the role of sesamin, sesamolin, and sesamol on hepatic lipid accumulation and explored the underlying mechanism via a well-established cell model. The results showed that 3 µg/ml of lignans could decrease the TG/TC contents and alleviate cellular oxidative stress, with an order of the lipid-lowering effect as sesamol > sesamin > sesamolin. The lignan-activated AMPK and PPAR signaling pathways enhanced gene and protein expressions related to fatty acid oxidation, cholesterol efflux, and catabolism. Meanwhile, treatment of the steatosis HepG2 cells with sesamin, sesamolin, and sesamol reduced lipid synthesis and cholesterol uptake, thus lowering intracellular lipogenesis in the process of NAFLD. Our data suggested that sesame lignans can attenuate oxidative stress and regulate lipid metabolism in liver cells, which may be potential therapeutic agents for treating the NAFLD. PRACTICAL APPLICATIONS: The present work demonstrated that sesame lignans can be used for dietary supplements or functional additives with excellent lipid-lowering effects. Furthermore, this study supplied potential molecular mechanisms involved in NAFLD treatment process, and also provided nutritional guidelines for sesame oil evaluation and selection.
Assuntos
Lignanas , Hepatopatia Gordurosa não Alcoólica , Sesamum , Benzodioxóis , Colesterol , Dioxóis , Células Hep G2 , Humanos , Lignanas/metabolismo , Lignanas/farmacologia , Lignanas/uso terapêutico , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo , Fenóis , Óleo de Gergelim/análise , Óleo de Gergelim/farmacologia , Sesamum/metabolismoRESUMO
This study investigated the effects of different microwave power (380 W, 540 W, 700 W) and time (0-10 min) on the minor bioactive components content and oxidative stability of perilla oil. The results indicated that fatty acids in perilla oil were slightly affected by microwave treatment. The oxidative stability of perilla oil increased with increasing microwave treatment intensity and the oil from perilla seeds treated at 700 W for 10 min had the highest oxidative stability. Compared with other microwave treatments, treatment with 700 W for 10 min resulted in significant increases in the total phytosterols content, Maillard reaction products and DPPH radical scavenging activity of perilla oil, while showed dramatic reductions in the total tocopherol content, phenolic compounds content and lipase activity. These results proved that microwave treatment of perilla seeds was an effective way to improve the quality of perilla oil.