ABSTRACT
Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti3C2@Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti3C2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti3C2@Qu nanocomposites were systematically investigated.
Subject(s)
Hyperthermia, Induced , Nanocomposites , Nanoparticles , Neoplasms , Nitrites , Transition Elements , Humans , Delayed-Action Preparations , Titanium/pharmacology , Phototherapy , Neoplasms/therapy , Cell Line, Tumor , Nanoparticles/chemistryABSTRACT
ETHNIC PHARMACOLOGICAL RELEVANCE: Cataract is the most common cause of blindness worldwide, a visual disorder caused by a clouded lens that seriously affects People's Daily lives. Age-related cataract (ARC) is the most common type of cataract due to long-term combined effects of many factors, and its pathogenesis is varied. At present, the surgery is the main treatment for cataracts, but it is still limited to the prevention, treatment of early cataracts and the postoperative complications care. While, its drug treatments are still in the stage of exploration and research. Traditional Chinese Medicine (TCM), a unique resource in China, is conceived under the guidance of traditional Chinese medicine theory and has little toxicity and side effects, but it has made great progress in the treatment and prevention of ARC. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of ARC in both traditional and modern medicines and summarizes the history and therapeutic effect of TCM on ARC including their formula, crude drugs and active components, and also the other auxiliary methods. METHODS: A number of recognized databases like SciFinder, PubMed, Science Direct, Google Scholar, and China National Knowledge Infrastructure (CNKI) were extensively explored by using keywords and phrases such as "cataract", "age-related cataract", "traditional medicine", "ethnopharmacology", "herbs", "medicinal plants", or other relevant terms, and the plants/phytoconstituents that are evaluated in the models of age-related cataract. As well as the current TCM adjuvant therapy used in the clinical treatment were summarized. RESULTS: TCM revealed to plays an active role in treating age-related cataract, via multi-pathway and multi-target, and can treat or delay ARC by inhibiting abnormal glucose metabolism, antioxidant damage, inhibiting LEC apoptosis, and so on, which is in concordance with the good effects of the global use of TCM in clinical application. Concerning the early prevention and treatment of cataract and postoperative complications, TCM and auxiliary methods remain to achieve better clinical effects. CONCLUSION: ARC belongs to the category of "Yuan Yi Nei Zhang" in TCM theory, showing that there are many causes of ARC including aging, and kidney-yang, spleen, sperm and blood deficiencies. At the same time, the viscera gradually decline, as well as yin or yang progressively become weak, especially in the elder people. So, TCM could be mainly based on liver, kidney, and spleen syndrome differentiation, personalizing diagnosis and treatment, following multiple targets, regulating fundamentally yin and yang, and thus justifying the advantages of Chinese medicine in the prevention and treatment of ARC.
Subject(s)
Cataract , Drugs, Chinese Herbal , Male , Humans , Aged , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Seeds , Cataract/drug therapy , Cataract/prevention & control , Postoperative Complications/drug therapyABSTRACT
This study aimed to evaluate the effects of music-based interventions on unilateral spatial neglect. Five databases were retrieved prior to May 5, 2022. A range of study designs were considered, including randomized controlled trials, controlled clinical trials, cohorts, and case series/reports. Types of music-based interventions were not limited. Methodological quality of randomized trials were evaluated using the RoB 2 tool, and the RoBiNT scale was utilized to assess the quality of case studies. Two authors independently summarized main results for assessments. Search strategies identified 186 potentially relevant articles, and 10 articles were collected for in-depth analysis. Preliminary results showed that USN patients performed better in cancellation tests than bisection tests after music-based intervention. In summary, pleasant music listening may have a beneficial effect on the visual attention of USN patients, and it can be hypothesized that this is related to the positive mood and emotions of patients induced by music. Music with a dynamic auditory stimulus as a new music listening programme in USN rehabilitation is worthy of further investigation. Instrument playing intervention can be considered as a multisensory stimulation to ameliorate neglect performance via multiple mechanisms. However, current results only support the short-term positive effects of music-based interventions on USN.
Subject(s)
Music Therapy , Music , Perceptual Disorders , Stroke , Humans , Music/psychology , Stroke/psychology , Emotions , Music Therapy/methods , Perceptual Disorders/etiology , Perceptual Disorders/rehabilitation , Randomized Controlled Trials as TopicABSTRACT
The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 patients with COPD and 36 healthy individuals in China. Multi-omics data were integrated using sequential mediation analysis, to assess in silico associations of the microbiome with two primary COPD inflammatory endotypes, neutrophilic or eosinophilic inflammation, mediated through microbial metabolic interaction with host gene expression. Hypotheses of microbiome-metabolite-host interaction were identified by leveraging microbial genetic information and established metabolite-human gene pairs. A prominent hypothesis for neutrophil-predominant COPD was altered tryptophan metabolism in airway lactobacilli associated with reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host interleukin-22 signalling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema and lung function decline, via macrophage-epithelial cell cross-talk mediated by interleukin-22. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.
Subject(s)
Host Microbial Interactions , Pulmonary Disease, Chronic Obstructive , Animals , Humans , Inflammation , Mice , Neutrophils , SputumABSTRACT
Methods: The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results: A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, ß-estradiol, berberine, wogonin, and ß-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion: In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.
ABSTRACT
BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Thrombosis , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/adverse effects , Humans , Liver Neoplasms/pathology , Phenylurea Compounds , Portal Vein/pathology , Prospective Studies , Quinolines , Retrospective Studies , Sorafenib/therapeutic use , Thrombosis/drug therapy , Thrombosis/therapy , Treatment OutcomeABSTRACT
BACKGROUND: De Quervain's disease is a kind of aseptic inflammation caused by repeated frictions of tendons in the tendon sheath of the styloid process of the radius. The main symptoms are protuberance and pain of the styloid process of the radius, accompanied by aggravation of pain during the movement of the wrist and thumb. The advantages of needle-knife are simple operation, obvious therapeutic effect and high safety. It can also be used to treat De Quervain's disease. Ultrasound gives a precise visualization of the thickness. The purpose of this study is to evaluate the efficacy and safety of ultrasound-guided needle-knife in the treatment of De Quervain's disease and to provide the latest basis for clinical application. METHODS: The computer will be used to search all randomized controlled trials (RCTs) about ultrasound-guided needle-knife treatment of De Quervain's disease in the following database: PubMed, Web of Science, Cochrane Library, Cochrane Central controlled Trials Registry (CENTER), EMBASE, China National knowledge Infrastructure (CNKI), Wanfang data, Chinese Biomedical Literature Database (CBM), VIP Database (VIP). The effectiveness and safety of ultrasound-guided needle-knife in the treatment of De Quervain's disease were evaluated with pain intensity, wrist function as the main index and wrist range of motion, adverse events and quality of life as the secondary index. Revman5.3 software was used for data processing. RESULTS: This study will provide the latest evidence for the Ultrasound-guided needle-knife for De Quervain's disease. CONCLUSION: The conclusion of this study is to evaluate the effectiveness and safety of ultrasound-guided needle-knife in the treatment of De Quervain's disease. UNIQUE INPLASY NUMBER: INPLASY202110094.
Subject(s)
Acupuncture Therapy/methods , De Quervain Disease/surgery , Ultrasonography, Interventional/methods , Humans , Network Meta-Analysis , Systematic Reviews as TopicABSTRACT
The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipocytes, Beige/drug effects , Adipocytes, Beige/metabolism , Adipocytes, White/drug effects , Adipocytes, White/metabolism , DNA-Binding Proteins/metabolism , Indole Alkaloids/pharmacology , Quinazolines/pharmacology , Transcription Factors/metabolism , Adipocytes, Beige/cytology , Adipocytes, White/cytology , Animals , Biological Products/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , In Vitro Techniques , Male , Mice , Mice, Transgenic , Models, Biological , Obesity/drug therapy , Obesity/genetics , Obesity/metabolism , Oxygen Consumption/drug effects , Signal Transduction/drug effects , Thermogenesis/drug effects , Thermogenesis/genetics , Thermogenesis/physiologyABSTRACT
We established a large-scale separation and purification platform to obtain kilogram amounts of natural compounds from the extraction of the fruiting bodies of C. militaris. Seven monomeric compounds, N6-(2-hydroxyethyl) adenosine (HEA), ergosterol (E), ergosta-7,22-diene-3,5,6-triol (EI), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol (ED),ergosta-7,22-dien-3ß,5α-dihydroxy-6-one (EO), (20S,22E,24R)-Eegosta-7,22-dien-3ß,5α,6ß,9α-tetraol (ET), and (24S)-5,22-stigmastadien-3ß-ol (SE), were harvested using different solvents, and the structure of each compound was identified. The activities and functions of the isolated compounds were tested by label-free, real-time cell analysis methods at the cellular level, and their antitumor effects were verified using mouse models of Lewis and H22 tumors. The anti-insomnia effect of HEA was tested in an anti-insomnia mouse model. The interactions between E and 8 A549 cell proteins were determined. The biosynthetic pathways of HEA and E, which possess pharmacologically active monomers, were determined. This platform can provide a theoretical basis for the further development and discovery of novel natural medicines.
Subject(s)
Antineoplastic Agents/pharmacology , Cordyceps/chemistry , Drugs, Chinese Herbal/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cordyceps/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Humans , Medicine, Chinese Traditional , Mice , Mice, Inbred Strains , Models, Molecular , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Structure-Activity RelationshipABSTRACT
Plant-derived bioactive compounds, often called phytochemicals, are active substances extracted from different plants. These bioactive compounds can release therapeutic potential abilities via reducing antitumor drugs side effects or directly killing cancer cells, and others also can adjust cancer initiation and progression via regulating microRNAs (miRNAs) expression, and miRNA can regulate protein-coding expression by restraining translation or degrading target mRNA. A mass of research showed that plant-derived bioactive compounds including tanshinones, astragaloside IV, berberine, ginsenosides and matrine can inhibit tumor growth and metastasis by rescuing aberrant miRNAs expression, which has influence on tumor progression, microenvironment and drug resistance in multifarious cancers. This review aims to provide a novel understanding of plant-derived bioactive compounds targeting miRNAs and shed light on their future clinical applications.
Subject(s)
Abietanes/therapeutic use , MicroRNAs/therapeutic use , Neoplasms/drug therapy , Phytochemicals/therapeutic use , Plants/chemistry , Abietanes/pharmacology , Humans , MicroRNAs/pharmacology , Molecular Structure , Phytochemicals/pharmacologyABSTRACT
In recent times, silver (Ag) based semiconductors have been gained a lot of attention as photocatalysts for industrial waste-water treatment owing to their strong visible-light absorbing capability and small bandgap energy. Therefore, herein, we have designed and utilized a one-pot hydrothermal approach to the synthesis of nano-sized AgBr covered potato-like Ag2MoO4 composite photocatalysts for the elimination of organic wastes from the aquatic environment. To achieve a high-performance photocatalyst, a sequence of AgBr/Ag2MoO4 composites were acquired with varying CTAB from 1 to 4 mmol. Furthermore, the photocatalytic activity of these photocatalysts was confirmed from decomposing of Rhodamine B (RhB) dye via visible-light elucidation. It can be noticed that AgBr/Ag2MoO4 composites exhibited significantly increased photocatalytic behaviour as compared with pure AgBr and Ag2MoO4. Surprisingly, the AgBr/Ag2MoO4 composite obtained from 2 mmol CTAB was eliminated the entire RhB dye with 25 min. Also, the recycling experiment indicates the AgBr/Ag2MoO4 composite has an excellent photo-stability. Accordingly, the as-acquired AgBr/Ag2MoO4 composite would be a suitable photocatalytic material for industrial waste-water purification.
Subject(s)
Silver , Solanum tuberosum , Bromides , Catalysis , Industrial Waste , Silver Compounds , Wastewater , WaterABSTRACT
Apple replant disease (ARD) is a soil-borne disease that leads to economic losses due to reduced plant growth and diminished fruit yields. Dopamine is involved in interactions between plants and pathogens. However, it remains unclear whether dopamine can directly stimulate defense responses to ARD. In this study, an exogenous dopamine treatment and dopamine synthetase MdTYDC (tyrosine decarboxylase) transgenic plants were used to verify the role of dopamine in treating ARD. First, 2-year-old apple trees (Malus domestica cv. Fuji), grafted onto rootstock M26, were grown in replant soils. The addition of dopamine (100 µM) to the soil promoted seedling growth and changed the accumulation of mineral elements in plants in replant soils. Such supplementation improved the activity of invertase, urease, proteinase and phosphatase under replant conditions. Sequencing analysis of 16S rDNA and internal transcribed spacer (ITS) rDNA revealed that dopamine had a slight influence on bacterial diversity but had an obvious effect on the fungal diversity in replant soils. The application of dopamine to replant soil changed the composition of bacterial and fungal communities. Second, overexpression of MdTYDC in apple plants alleviated the effects of ARD. MdTYDC transgenic lines exhibited mitigated ARD through inhibited degradation of photosynthetic pigment, maintaining the stability of photosystems I and II and improving the antioxidant system. Furthermore, overexpression of MdTYDC improved arbuscular mycorrhizal fungi colonization by improving the accumulation of soluble sugars under replant conditions. Together, these results demonstrated that dopamine enhances the tolerance of apples to ARD.
Subject(s)
Malus , Dopamine , Malus/genetics , Plant Roots/genetics , Soil , Soil MicrobiologyABSTRACT
Oxalate is commonly employed as adjuvant of pesticide agent, causing renal injury of human even in trace residues. Despite the great achievements of the existing point-of-care testing (POCT) technology, accurate on-site screening of oxalate remains a tricky issue. To this aim, we proposed a "lab in a tube" platform which integrated portable hydrogel kit with smartphone for real-time monitoring of oxalate to achieve quantitatively precise analysis. In this work, a stimuli-responsive hydrogel-based kit was constructed via embedding manganese dioxide (MnO2) nanosheets into sodium alginate hydrogel system. Based on the intrinsic oxidase-like activity, MnO2 nanosheets-based nanozyme triggered color reaction by introducing a common sensing probe 3,3',5,5'-tetramethylbenzidine. Meanwhile, the presence of oxalate would decompose MnO2 nanosheets, inducing the decrease of nanozyme activity, which resulted in the color response of portable kit. Coupling with ImageJ software, the image information of kit captured via smartphone could be transduced into the hue intensity, which provided a directly quantitative tool to detect oxalate with a detection limit of 8.0 µmol L-1. This portable smartphone biosensor was successfully applied for screening urine sample within 10 min for high-throughput analysis (twelve samples) without the need for any advanced analytical instruments. Based on the merits of simple operation, cost-efficiency, and good selectivity, the availability of the miniaturized biosensor platform for POCT will achieve the requirements of routine screening and disease prevention.
Subject(s)
Biosensing Techniques , Hydrogels , Humans , Manganese Compounds , Oxalates , Oxides , SmartphoneABSTRACT
OBJECTIVE: To investigate the factors affecting counting and collection efficiency of the final product- mononuclear cells (MNCs) in the collection of mononuclear cells for tumor cell biotherapy. METHODS: The collected data of 142 tumor patients and healthy donors were analyzed, including age, sex, height, weight, BMI, the total blood volume, diagnostic category, vascular access, operator, final product volume, ACD anticoagulant usage, flow rate and circulation times, pre-apheresis Hb, RBC, Plt, WBC, lymphocyte count, monocyte count, neutrophil count, circulating blood volume without anticoagulant, final product MNC and collection efficiency of MNC. CE(collection efficiency)%= final product MNC×100/(pre-apheresis MNC×circulating blood volume without anticoagulant). The factors affecting final products MNC and CE of MNC were detected by T test and multiple linear regression analysis. RESULTS: The CE of tumor patients was higher than that of healthy donors ï¼24.41±1.91,vs 20.01±0.99)ï¼(P=0.043ï¼, and CE of MNC was different among different operators (P=0.01, H=18.59). There was a positive correlation of the final MNC with the volume of final product, ACD anticoagulant usage and pre-apheresis lymphocyte count (P= 0.00, P= 0.01, P= 0.00ï¼ r=0.811); CE of MNC negatively correlated with flow rate and pre-apheresis RBC, but positively correlated with operator's working age and ACD anticoagulant usage (P=0.01, P=0.04, P=0.03, P= 0.00, r=0.495). CONCLUSION: more higher pre-apheresis lymphocyte , more amount of the final product and ACD anticoagulant usage, and more high the final MNC. During the collecting process, more ACD anticoagulant usage and more high operator's seniority, lead to the higher MNC'S CE; while more high pre-apheresis RBC and more fast flow rate, cause the lower the CE of MNC.
Subject(s)
Biological Therapy , Blood Component Removal , Humans , Leukapheresis , Leukocyte Count , Leukocytes, Mononuclear , Lymphocytes , Tissue DonorsABSTRACT
Enterovirus 71 (EV71) which commonly caused the hand-foot-mouth disease (HFMD) has become one of public health challenges worldwide. However, no effective vaccines or drugs for this disease has been developed. Thus, there is an urgent need to find a new strategy for treating the EV71 infection. Oseltamivir (OT) is an effective antiviral agent, but continuous use of oseltamivir leads to a diminished therapeutic effect in the clinic. In order to improve the antiviral activity of oseltamivir, oseltamivir was loaded onto surfaces of selenium nanoparticles (SeNPs) to fabricate a functionalized antiviral nanoparticles SeNPs@OT. The size of SeNPs@OT was tested by TEM and dynamic light scattering. The chemical structure and elemental composition of SeNPs@OT were analyzed by FT-IR and EDX, respectively. SeNPs@OT exhibited good stability and effective drug release in serum and PBS. SeNPs@OT efficiently entered into human astrocyte U251 cells (host cells) via clathrin-associated endocytosis and inhibited EV71 proliferation, which could protect EV71-infected U251 cells from apoptosis through mitochondrial pathway. Furthermore, SeNPs@OT inhibited EV71 activity probably by reducing the generation of reactive oxygen species in EV71-infected U251 cells. Interestingly, SeNPs obviously enhanced antiviral activity of oseltamivir in the anti-EV71 cell model. Taken together, SeNPs@OT is a promising antiviral drug candidate for EV71 infection.
Subject(s)
Astrocytoma/pathology , Enterovirus A, Human/drug effects , Nanoparticles/chemistry , Oseltamivir/chemistry , Oseltamivir/pharmacology , Selenium/chemistry , Antiviral Agents/adverse effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Endocytosis/drug effects , Humans , Oseltamivir/adverse effects , Reactive Oxygen Species/metabolismABSTRACT
Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Autophagy/drug effects , Drug Resistance, Neoplasm/drug effects , Drugs, Chinese Herbal/pharmacology , Gefitinib/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Autophagy/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Survival/drug effects , Down-Regulation , Drugs, Chinese Herbal/administration & dosage , Gefitinib/administration & dosage , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Signal Transduction , Up-RegulationABSTRACT
Major depressive disorder (MDD) is a recurrent, chronic mental illness. While music therapy has been established as an effective treatment for MDD patients, the effects of this therapy on brain function remain unclear. This research employed near-infrared spectroscopy (NIRS) to explore the effects of music therapy on brain activity in mild or moderate MDD patients and to illustrate the potential mechanism of music therapy. Methods: Fifteen MDD patients and fifteen healthy controls (HC) underwent neuropsychological evaluations and NIRS measurements. All participants were treated with continuous music therapy for 10 days. Subsequently, all individuals were evaluated with neuropsychological assessments and NIRS measurements again. Results: The verbal fluency task (VFT) performances of the participants yielded significantly higher scores after music therapy in terms of vegetables, four-footed animals and fruit blocks. After the music treatment, the NIRS data showed that the mean active oxy-Hb values of channels 21, 23, 19, and 41 were significantly increased in both the MDD and HC groups. The MDD group showed significant activation in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC) after music therapy. The results indicate that music therapy could improve the brain function of MDD patients.
Subject(s)
Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/therapy , Hemodynamics , Music Therapy , Prefrontal Cortex/blood supply , Adolescent , Adult , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Prefrontal Cortex/diagnostic imaging , Spectroscopy, Near-Infrared , Young AdultABSTRACT
INTRODUCTION: Ribavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV). METHODS AND RESULTS: MTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addition, phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo experiments indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochemical test revealed an identical result with the in vitro experiment that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment. CONCLUSION: Taken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.
Subject(s)
Apoptosis/drug effects , Caspase 3/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Nanoparticles/chemistry , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Ribavirin/therapeutic use , Selenium/therapeutic use , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cell Survival/drug effects , Dogs , Enzyme Activation/drug effects , Female , Humans , Influenza A Virus, H1N1 Subtype/growth & development , Madin Darby Canine Kidney Cells , Mice, Inbred BALB C , Nanoparticles/ultrastructure , Ribavirin/pharmacology , Selenium/pharmacology , Signal Transduction/drug effectsABSTRACT
Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.
Subject(s)
Antineoplastic Agents, Phytogenic , Cell Transformation, Neoplastic/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Glycyrrhiza uralensis/chemistry , Phytotherapy , Polysaccharides/isolation & purification , Polysaccharides/pharmacology , Animals , Cell Line, Tumor , Disease Models, Animal , Fecal Microbiota Transplantation , Male , Mice, Inbred BALB CABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Camptosorus sibiricus Rupr (CSR) is a widely used herbal medicine with antivasculitis, antitrauma, and antitumor effects. However, the effect of CSR aqueous extract on B[a]P-initiated tumorigenesis and the underlying mechanism remain unclear. Moreover, the compounds in CSR aqueous extract need to be identified and structurally characterized. AIM OF THE STUDY: We aim to investigate the chemopreventive effect of CSR and the underlying molecular mechanism. MATERIALS AND METHODS: A B[a]P-stimulated normal cell model (BEAS.2B) and lung adenocarcinoma animal model were established on A/J mice. In B[a]P-treated BEAS.2B cells, the protective effects of CSR aqueous extract on B[a]P-induced DNA damage and ROS production were evaluated through flow cytometry, Western blot, real-time quantitative PCR, single-cell gel electrophoresis, and immunofluorescence. Moreover, a model of B[a]P-initiated lung adenocarcinoma was established on A/J mice to determine the chemopreventive effect of CSR in vivo. The underlying mechanism was analyzed via immunohistochemistry and microscopy. Furthermore, the new compounds in CSR aqueous extract were isolated and structurally characterized using IR, HR-ESI-MS, and 1D and 2D NMR spectroscopy. RESULTS: CSR effectively suppressed ROS production by re-activating Nrf2-mediated reductases HO-1 and NQO-1. Simultaneously, CSR attenuated the DNA damage of BEAS.2B cells in the presence of B[a]P. Moreover, CSR at 1.5 and 3â¯g/kg significantly suppressed tumorigenesis with tumor inhibition ratios of 36.65% and 65.80%, respectively. The tumor volume, tumor size, and multiplicity of B[a]P-induced lung adenocarcinoma were effectively decreased by CSR in vivo. After extracting and identifying the compounds in CSR aqueous extract, three new triterpene saponins were isolated and characterized structurally. CONCLUSIONS: CSR aqueous extract prevents lung tumorigenesis by exerting dual effects against ROS and DNA damage, suggesting that CSR is a novel and effective agent for B[a]P-induced carcinogenesis. Moreover, by isolating and structurally characterizing three new triterpene saponins, our study further standardized the quality of CSR aqueous extract, which could widen CSR clinical applications.