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PURPOSE: To explore the behavioral intention of breast cancer patients undergoing chemotherapy to prevent PICC-related thrombosis based on the theory of planned behavior (TPB). METHODS: This qualitative study employed purposive sampling and conducted semi-structured interviews with 14 breast cancer patients undergoing chemotherapy in the outpatient chemotherapy ward of a tertiary A-level comprehensive hospital in Beijing from July to August 2023. Data were analyzed using Colaizzi's descriptive analysis framework. RESULTS: Data analysis identified 10 themes that were derived from 4 aspects. Regarding behavioral attitude, three themes were condensed: (1) Considering the benefits of preventive measures, (2) Simple and easy preventive measures, and (3) Underestimating the importance of PICC-related thrombosis prophylaxis. Subjective norms yielded two main themes and five sub-themes: (1) Support from those close to the patient motivates adherence to prophylaxis (support from the patient's family, healthcare professionals, and other patients) and (2) Patients are influenced by personal factors to form an internal driving force (physical symptoms, fear of PICC-related thrombosis). Regarding perceived behavioral control, three main themes and four sub-themes were extracted: (1) Obstacles before actual prevention exercise (prevention information, hard-to-remember information), (2) Forgetfulness is the main obstacle factor, and (3) Wanting to overcome barriers to adhere to regular prevention (confidence to overcome obstacles, hope to get support). CONCLUSIONS: The impediments and facilitators identified in this study may provide a scientific foundation for subsequent targeted non-pharmacological preventive interventions for PICC-related thrombosis based on TPB in breast cancer patients undergoing chemotherapy. Special interventions should be designed for the patients in three areas: the patients themselves, the supporters around the patient, and the healthcare professionals.
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Neoplasias da Mama , Intenção , Pesquisa Qualitativa , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Trombose/prevenção & controle , Trombose/etiologia , Idoso , Entrevistas como Assunto , Teoria do Comportamento PlanejadoRESUMO
Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum. We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.
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Estações do Ano , Caramujos , Animais , China/epidemiologia , Caramujos/parasitologia , Schistosoma japonicum/fisiologia , Densidade Demográfica , Lagos/parasitologia , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/transmissão , Temperatura , Teorema de Bayes , Esquistossomose/epidemiologia , Esquistossomose/transmissão , Esquistossomose/parasitologia , Meio AmbienteRESUMO
Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.
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Phytophthora blight of pepper, which is caused by the notorious oomycete pathogen Phytophthora capsici, is a serious disease in global pepper production regions. Our previous study had identified two WRKY transcription factors (TFs), CaWRKY01-10 and CaWRKY08-4, which are prominent modulators in the resistant pepper line CM334 against P. capsici infection. However, their functional mechanisms and underlying signaling networks remain unknown. Herein, we determined that CaWRKY01-10 and CaWRKY08-4 are localized in plant nuclei. Transient overexpression assays indicated that both CaWRKY01-10 and CaWRKY08-4 act as positive regulators in pepper resistance to P. capsici. Besides, the stable overexpression of CaWRKY01-10 and CaWRKY08-4 in transgenic Nicotiana benthamiana plants also significantly enhanced the resistance to P. capsici. Using comprehensive approaches including RNA-seq, CUT&RUN-qPCR, and dual-luciferase reporter assays, we revealed that overexpression of CaWRKY01-10 and CaWRKY08-4 can activate the expressions of the same four Capsicum annuum defense-related genes (one PR1, two PR4, and one pathogen-related gene) by directly binding to their promoters. However, we did not observe protein-protein interactions and transcriptional amplification/inhibition effects of their shared target genes when coexpressing these two WRKY TFs. In conclusion, these data suggest that both of the resistant line specific upregulated WRKY TFs (CaWRKY01-10 and CaWRKY08-4) can confer pepper's resistance to P. capsici infection by directly activating a cluster of defense-related genes and are potentially useful for genetic improvement against Phytophthora blight of pepper and other crops.
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Capsicum , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Phytophthora , Doenças das Plantas , Proteínas de Plantas , Fatores de Transcrição , Phytophthora/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Capsicum/genética , Capsicum/microbiologia , Capsicum/imunologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/microbiologia , Plantas Geneticamente Modificadas/imunologiaRESUMO
Phytophthora blight of pepper is a notorious disease caused by the oomycete pathogen Phytophthora capsici, which poses a great threat to global pepper production. MicroRNA (miRNA) is a class of non-coding small RNAs that regulate gene expressions by altering the translation efficiency or stability of targeted mRNAs, which play important roles in the regulation of a plant's response to pathogens. Herein, time-series mRNA-seq libraries and small RNA-seq libraries were constructed using pepper roots from the resistant line CM334 and the susceptible line EC01 inoculated with P. capsici at 0, 6, 24, and 48 h post-inoculation, respectively. For mRNA-seq analysis, a total of 2159 and 2971 differentially expressed genes (DEGs) were identified in CM334 and EC01, respectively. For miRNA-seq analysis, 491 pepper miRNAs were identified, including 330 known miRNAs and 161 novel miRNAs. Among them, 69 and 88 differentially expressed miRNAs (DEMs) were identified in CM334 and EC01, respectively. Examination of DEMs and their targets revealed 22 regulatory networks, predominantly featuring up-regulated miRNAs corresponding to down-regulated target genes. Notably, these DEM-DEG regulatory networks exhibited significant overlap between CM334 and EC01, suggesting that they might contribute to pepper's basal defense against P. capsici. Furthermore, five selected DEMs (miR166, miR1171, miR395, miR530 and miRN2) and their target genes underwent qRT-PCR validation, confirming a consistent negative correlation in the expression patterns of miRNAs and their targets. This comprehensive analysis provides novel insights into the regulatory networks of miRNAs and their targets, offering valuable contributions to our understanding of pepper's defense mechanisms against P. capsici.
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When the electric field strength (E) surpasses a certain threshold, secondary droplets are generated during the coalescence between water droplets in oil and the oil-water interface (so-called the droplet-interface partial coalescence phenomenon), resulting in a lower efficiency of droplet electrocoalescence. This study employs molecular dynamics (MD) simulations to investigate the droplet-interface partial coalescence phenomenon under direct current (DC) electric fields. The results demonstrate that intermolecular interactions, particularly the formation of hydrogen bonds, play a crucial role in dipole-dipole coalescence. Droplet-interface partial coalescence is categorized into five regimes based on droplet morphology. During the contact and fusion of the droplet with the water layer, the dipole moment of the droplet exhibits alternating increases and decreases along the electric field direction. Electric field forces acting on sodium ions and the internal interactions within droplets promote the process of droplet-interface partial coalescence. High field strengths cause significant elongation of the droplet, leading to its fragmentation into multiple segments. The migration of hydrated ions has a dual impact on the droplet-interface partial coalescence, with both facilitative and suppressive effects. The time required for droplet-interface partial coalescence initially decreases and subsequently increases as the field strength increases, depending on the competitive relationship between the extent of droplet stretching and the electric field force. This work provides molecular insights into the droplet-interface coalescence mechanisms in water-in-oil emulsions under DC electric fields.
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Introduction: Although various therapies have been adopted to treat cancer, metastasis of tumor cells still is a big challenge that compromises therapeutic benefits. Methods: We herein report an injectable drug-loaded hybrid hydrogel that can achieve sonodynamic therapy (SDT) and chemodyanmic therapy (CDT) combined action and suppression of tumor metastasis. This alginate (ALG)-based hydrogel (termed as AMPS) contains manganese dioxide (MnO2) nanoparticles as the CDT agents, an organic polymer as the sonosensitizer, and a SIS3 drug as metastasis inhibitor. Results: AMPS is formed via the chelation of ALG by Ca2+ in tumor microenvironment, in which MnO2 nanoparticles mediate CDT via Fenton-like reaction and the organic polymers enable SDT under ultrasound (US) irradiation by generating singlet oxygen (1O2), allowing for combinational action of CDT and SDT. In addition, SIS3 is released from AMPS hydrogels to inhibit the metastasis of tumor cells. As such, the AMPS enables a combinational action of SDT and CDT to greatly inhibit the growths of subcutaneous tumors in living mice and also completely suppress the tumor metastasis in lungs and livers. Conclusion: This study thus offers a hybrid hydrogel platform for combinational therapy and metastasis suppression simultaneously.
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Although immunotherapy has achieved great success in the treatment of a variety of tumors, its efficacy for glioblastoma (GBM) is still limited. Both the immunosuppressive tumor microenvironment (TME) and poor penetration of immunotherapeutic agents into tumors contributed to the poor anti-glioma immunity. Herein, we develop an injectable prodrug-loaded hydrogel delivery system with sono-activatable properties for sonodynamic therapy (SDT)-triggered immunomodulation for GBM treatment. The prodrug alginate hydrogels (APN), which contain semiconducting polymer nanoparticles (SPNs) and the NLG919 prodrug linked by singlet oxygen (1O2)-cleavable linkers, are in situ formed via coordination of alginate solution with Ca2+ in the TME. SPNs serve as sonosensitizers to produce 1O2 upon ultrasound (US) irradiation for SDT. The generated 1O2 not only induce immunogenic cell death, but also break 1O2-cleavable linkers to precisely activate the NLG919 prodrug. Antitumor immunity is significantly amplified due to the reversal of immunosuppression mediated by indolamine 2,3-dioxygenase-dependent tryptophan metabolism. This smart prodrug hydrogel platform potently inhibits tumor growth in orthotopic glioma-bearing mice. Collectively, this work provides a sono-activatable hydrogel platform for precise sono-immunotherapy against GBM.
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Glioblastoma , Glioma , Nanopartículas , Neoplasias , Pró-Fármacos , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Polímeros , Neoplasias/terapia , Imunoterapia , Alginatos , Hidrogéis , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Chemodynamic therapy (CDT) is an emerging treatment strategy for cancer, but the low therapeutic efficacy and potential side effects still limit its applications. In this study, we report a semiconducting polymer nanocatalyst (PGFe) that can generate reactive oxygen species (ROS) only upon near-infrared (NIR) light-activation for photodynamic therapy (PDT)-synergized CDT. Such PGFe consists of a semiconducting polymer as a photosensitizer, iron oxide (Fe3O4) nanoparticles as CDT agents, and glucose oxidase (GOx), all of which are loaded into a singlet oxygen (1O2)-responsive nanocarrier. Under NIR laser irradiation, PGFe produces 1O2 through a photosensitizer-mediated PDT effect, and the produced 1O2 destroys the 1O2-responsive nanocarriers, leading to controlled releases of Fe3O4 nanoparticles and GOx. In a tumor microenvironment, GOx catalyzes glucose degradation to form hydrogen peroxide (H2O2), and thus the CDT effect of Fe3O4 nanoparticles is greatly improved. As such, an amplified ROS level in tumor cells is obtained by PGFe to induce cell death. PGFe can be utilized to treat subcutaneous 4T1 tumors, observably inhibiting the tumor growth and suppressing lung and liver metastasis. This study thus provides a NIR light-activated ROS generation strategy for precise and effective treatments of tumors.
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Peróxido de Hidrogênio , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio , Raios Infravermelhos , Glucose Oxidase , PolímerosRESUMO
Inducing immunogenic cell death (ICD) by sonodynamic therapy (SDT) is promising for cancer immunotherapy, which however is inefficient due to oxygen depletion that compromises SDT effect and mediates recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). The fabrication of sono-activatable semiconducting polymer nanopartners (SPNTi ) to simultaneously augment ICD and alleviate MDSCs for immunotherapy is reported. A sonodynamic semiconducting polymer, hydrophobic hypoxia-responsive tirapazamine (TPZ)-conjugate, and MDSC-targeting drug (ibrutinib) are encapsulated inside such SPNTi with surface shell of a singlet oxygen (1 O2 )-cleavable amphiphilic polymer. TPZ and ibrutinib serve as drug partners to enlarge immunotherapeutic effect. Upon sono-activation, SPNTi generate 1 O2 to break 1 O2 -cleavable polymers for in situ liberations of TPZ-conjugate and ibrutinib in tumor sites, and oxygen is consumed to create severe hypoxic tumor microenvironment, in which, TPZ-conjugate is activated for augmenting ICD action, while ibrutinib alleviates MDSCs for promoting antitumor immunological effect. In a bilateral tumor mouse model, SPNTi -mediated sono-activatable immunotherapy results in growth restraints of primary and distant tumors and noteworthy precaution of tumor metastases. This study thus provides a sono-activatable immunotherapeutic strategy with high precision and safety for cancer via overcoming post-treatment hypoxia and targeting MDSCs.
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Células Supressoras Mieloides , Neoplasias , Animais , Camundongos , Células Supressoras Mieloides/metabolismo , Polímeros/farmacologia , Morte Celular Imunogênica , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tirapazamina/metabolismo , Imunoterapia , Hipóxia/metabolismo , Oxigênio/metabolismo , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Diabetic cardiomyopathy (DCM) is highly prevalent and increases the risk of heart failure and sudden death. Therefore, proper and effective treatments for DCM are in urgent demand. Danlou tablet (Dan) is reported to confer protective effects on several heart diseases. However, to our knowledge, whether Dan provides protection against DCM is unclear. In this study, we explored the effect of Dan on DCM with the in vitro DCM model using AC16 cardiomyocytes. We found that Dan treatment significantly reduced cardiomyocyte apoptosis and oxidative stress in high-glucose (HG)-treated cardiomyocytes, as evidenced by decreased Annexin V-FITC+ cardiomyocytes, intracellular reactive oxygen species (ROS) levels, Bax/Bcl2 ratio, and cleaved-Caspase3/Caspase3 ratio. Interestingly, Dan treatment caused a decreased level of microRNA-34a (miR-34a), which could enhance cardiomyocyte apoptosis. Furthermore, miR-34a mimic blocked Dan's effect in apoptosis prevention. Finally, we observed that the miR-34a mimic effectively decreased the level of sirtuin 1 (SIRT1), while the miR-34a inhibitor increased the level of SIRT1. And downregulation of SIRT1 effectively reversed the effect of miR-34a inhibitor on cardiomyocyte apoptosis. Taken together, our study showed that Dan prevented HG-induced cardiomyocyte apoptosis through downregulating miR-34a and upregulating SIRT1. Our study has provided experimental support for the potential use of Dan in treating DCM. Further detailed study of Dan and the underlying mechanisms may shed light on the prevention and treatment of DCM.
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With permanent heart muscle injury or death, myocardial infarction (MI) is complicated by inflammatory, proliferation and remodeling phases from both the early ischemic period and subsequent infarct expansion. Though in situ re-establishment of blood flow to the infarct zone and delays of the ventricular remodeling process are current treatment options of MI, they fail to address massive loss of viable cardiomyocytes while transplanting stem cells to regenerate heart is hindered by their poor retention in the infarct bed. Equipped with heart-specific mimicry and extracellular matrix (ECM)-like functionality on the network structure, hydrogels leveraging tissue-matching biomechanics and biocompatibility can mechanically constrain the infarct and act as localized transport of bioactive ingredients to refresh the dysfunctional heart under the constant cyclic stress. Given diverse characteristics of hydrogel including conductivity, anisotropy, adhesiveness, biodegradability, self-healing and mechanical properties driving local cardiac repair, we aim to investigate and conclude the dynamic balance between ordered architectures of hydrogels and the post-MI pathological milieu. Additionally, our review summarizes advantages of heart-tailored architectures of hydrogels in cardiac repair following MI. Finally, we propose challenges and prospects in clinical translation of hydrogels to draw theoretical guidance on cardiac repair and regeneration after MI.
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Hidrogéis , Infarto do Miocárdio , Humanos , Hidrogéis/química , Infarto do Miocárdio/terapia , Miócitos Cardíacos , Remodelação Ventricular , Matriz Extracelular/patologia , MiocárdioRESUMO
Microglia are the main immune cells of the central nervous system (CNS) and comprise various model systems used to investigate inflammatory mechanisms in CNS disorders. Currently, shaking and mild trypsinization are widely used microglial culture methods; however, the problems with culturing microglia include low yield and a time-consuming process. In this study, we replaced normal culture media (NM) with media containing 25% fibroblast-conditioned media (F-CM) to culture mixed glia and compared microglia obtained by these two methods. We found that F-CM significantly improved the yield and purity of microglia and reduced the total culture time of mixed glia. The microglia obtained from the F-CM group showed longer ramified morphology than those from the NM group, but no difference was observed in cell size. Microglia from the two groups had similar phagocytic function and baseline phenotype markers. Both methods yielded microglia were responsive to various stimuli such as lipopolysaccharide (LPS), interferon-γ (IFN-γ), and interleukin-4 (IL-4). The current results suggest that F-CM affect the growth of primary microglia in mixed glia culture. This method can produce a high yield of primary microglia within a short time and may be a convenient method for researchers to investigate inflammatory mechanisms and some CNS disorders.
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Microglia , Neuroglia , Meios de Cultivo Condicionados/farmacologia , Células Cultivadas , Fibroblastos , Lipopolissacarídeos/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt, Arabia, Greece, and China, PEOs were traditional used in aromatherapy for various health disorders, including pain and inflammation. AIM OF THE STUDY: In this review, we provide an overview of the anti-inflammatory effects of PEOs and the underlying mechanisms associated with anti-inflammatory effects using in vitro and in vivo models. Further, clinical trials associated with PEOs were explored. MATERIALS AND METHODS: The literature search was performed using various web-based tools and databases like Google Scholar, Web of Science, PubMed, CNKI and SCOPUS. The keywords used for conducting the literature review were general terms like "essential oils" followed by (AND) the subject of interest like "in vitro and/or in vivo anti-inflammatory models," "inflammatory response," "inflammatory indicators," "pro-inflammatory cytokines," "signaling pathway," "anti-inflammatory mechanism," "toxicology and side effects" and "clinical trials." The articles selected were published between 2017 and 2022. The articles prior to 2017 were only considered if they were associated with molecular mechanisms or signaling pathways involved in the inflammatory responses. RESULTS: In vitro and in vivo inflammation models have been used to study the anti-inflammatory effects of 48 PEOs. Studies have reported that PEOs targets and inhibit multiple dysregulated signaling pathways associated with inflammation, including Toll-like receptors, nuclear transcription factor-κ B, mitogen-activated protein kinases, Nod-like receptor family pyrin domain containing 3, and auxiliary pathways like the nuclear factor erythroid 2-related factor 2/antioxidant response element and Janus kinase/signal transducers and activators of transcription) signaling pathways. CONCLUSION: PEOs extracted from different plant materials had varied qualitative and quantitative compositions of biologically active compounds. Different anti-inflammatory potentials and different molecular signal transduction have been attributed to PEOs-derived bioactive compounds with different chemical structures. The data on therapeutic efficacy and the long-term side effects of PEOs as an anti-inflammatory drug are still unknown due to the lack of clinical trials on PEOs. There is still insufficient evidence to draw conclusions on anti-inflammatory properties of PEOs without promising outcomes from clinical trials.
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Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/química , Óleos de Plantas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologiaRESUMO
The exploration of safe antibiotic substitutes is one of the research hotspots in animal husbandry. Adding suitable plant essential oils into feed could improve the growth performance and immune capacity of animals. In order to make plant essential oil play a better role in feed application, sodium alginate and chitosan were used as the wall materials, and blended plant essential oils (BEO) as the core material to prepare BEO microcapsules by the sharp-hole condensation method. On the basis of single-factor experiments, the optimal preparation conditions for BEO microcapsules were obtained by response surface experiments. The physicochemical properties were characterized and analyzed by Fourier-transform infrared spectroscopy (FTIR) and field scanning electron microscope (FSEM). Meanwhile, the release mechanism was studied by simulating a gastrointestinal sustained-release experiment. The results showed that under the optimal preparation conditions, the encapsulation efficiency of BEO microcapsules could reach 80.33 ± 2.35%. FTIR and SEM analysis displayed that the microcapsules obtained had uniform color and size and a complete and compact structure. In vitro study indicated that the release amount of BEO microcapsules in the simulated intestinal fluid is higher than that in the simulated intestinal fluid, which was consistent with animal digestive and absorptive characteristics.
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Quitosana , Óleos Voláteis , Animais , Cápsulas/química , Óleos Voláteis/química , Quitosana/química , Preparações de Ação Retardada/química , Óleos de Plantas/química , Alginatos/química , AntibacterianosRESUMO
Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, is non-apoptotic programmed cell death highly relevant to tumor development. It was found to manipulate oncogenes and resistant mutations of cancer cells via lipid metabolism pathways converging on phospholipid glutathione peroxidase (GPX4) that squanders lipid peroxides (L-OOH) to block the iron-mediated reactions of peroxides, thus rendering resistant cancer cells vulnerable to ferroptotic cell death. By accumulating ROS and lipid peroxidation (LPO) products to lethal levels in tumor microenvironment (TME), ferroptosis-driven nanotherapeutics show a superior ability of eradicating aggressive malignancies than traditional therapeutic modalities, especially for the drug-resistant tumors with high metastasis tendency. Moreover, Fenton reaction, inhibition of GPX-4, and exogenous regulation of LPO are three major therapeutic strategies to induce ferroptosis in cancer cells, which were generally applied in ferroptosis-driven nanotherapeutics. In this review, we elaborate current trends of ferroptosis-driven nanotherapeutics to reverse drug resistance of tumors in anticancer fields at the intersection of cancer biology, materials science, and chemistry. Finally, their challenges and perspectives toward feasible translational studies are spotlighted, which would ignite the hope of anti-resistant cancer treatment.
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Ferroptose , Neoplasias , Resistência a Medicamentos , Humanos , Ferro/metabolismo , Neoplasias/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Espécies Reativas de Oxigênio/metabolismo , Microambiente TumoralRESUMO
The economic, environmental and social sustainability of Dutch dairy farms have attracted increasing societal concern in the past decades. In this paper, we propose a recently developed dynamic Luenberger indicator based on the by-production model to measure dynamic productivity growth in the economic, environmental and social dimensions of sustainability of Dutch dairy farms. Subsequently, we investigate the statistical associations between productivity growth and socio-economic factors using the OLS bootstrap regression model. We find that dairy farms have suffered a decline in dynamic sustainable productivity growth, especially in the environmental dimension where it is more pronounced than in the economic and social dimensions. Furthermore, we find that both technical and scale inefficiency change contribute to the decline of environmental productivity growth. Specialization and government support are associated with a higher economic and environmental sustainability productivity growth, and with, a decreased growth of social sustainable productivity. We found no significant association between the age of the oldest entrepreneur, financial structure, farm size or cost of advisory service and dynamic productivity growth in the three sustainability dimensions. The results provide insights into potential pathways towards improving the three pillars of sustainability.
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Indústria de Laticínios/economia , Fazendas/economia , Leite , Crescimento Sustentável , Animais , Bovinos , Países BaixosRESUMO
To study the material basis and mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease(AD) based on GC-MS and network pharmacology. Ingredients of volatile oil from A.oxyphylla were analyzed by GC-MS. Targets of those ingredients were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Relevant targets of AD were obtained through such databases as DrugBank, STITCH, OMIM. Intersection targets of ingredients and diseases were obtained by Online Venny map, and PPI network was established by STRING to screen out core targets. Gene ontology(GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. The "ingredients-target-pathway" network was constructed by software Cytoscape 3.8.1 to screen out potential active ingredients of volatile oil from A.oxyphylla in the treatment of AD. The results showed that a total of 6 active ingredients were screened from the volatile oil of A.oxyphylla by GC-MS, 17 targets corresponding to 6 active ingredients were found in TCMSP database, and 3 448 AD targets were found in DrugBank database. "Ingredients-target-pathway" network and PPI network showed there were 4 potential active ingredients in the treatment of AD and 4 core targets. GO analysis and KEGG analysis showed 34(P<0.05) and 5(P<0.05) pathways, respectively, including nerve ligand receptor interaction, calcium signaling pathway, cholinergic synapse and 5-hydroxytryptaminergic synapse. This suggested that volatile oil from A.oxyphylla could synergistically treat AD by regulating calcium balance, cholinergic balance and phosphorylation. This study provided reference and guidance for further study of volatile oil from A.oxyphylla in the treatment of AD.
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Alpinia , Doença de Alzheimer , Medicamentos de Ervas Chinesas , Óleos Voláteis , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Simulação de Acoplamento MolecularRESUMO
This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 µL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 µL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.
Assuntos
Citrus , Medicamentos de Ervas Chinesas , Óleos Voláteis , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Óleos Voláteis/farmacologiaRESUMO
BACKGROUND: Venous thromboembolism is a severe preventable complication among orthopaedic surgical patients. Integrating therapeutic guidelines into clinical practice can help improve patient safety and reduce the burden of this pathology. Improving the quality of patient care is important for bridging the gap between the prophylaxis for venous thromboembolism and therapeutic guidelines. OBJECTIVES: This study aimed at evaluating the knowledge, attitude, and venous thromboembolism and prophylaxis practices of Chinese orthopaedic nurses to guide quality care improvements. METHODS: The data used in this study are secondary data obtained from a multicentric survey. An anonymous questionnaire was used to measure the attitude and knowledge of venous thromboembolic prophylaxis among orthopaedic nurses. VTE prophylactic practices were extracted from medical records within the electronic case report form immediately after the nurses' investigations. The STROBE statement for observational studies was applied. RESULTS: Results indicated that although 94.0% of the responding nurses had attended training courses in their wards, a majority of them (68.9%) achieved a median knowledge score of 7 points or below (range 0-9). Knowledge regarding the proper use of prophylaxis, identification of risk factors, signs and symptoms for pulmonary embolism was limited. Self-reported attitudes underestimate the relationships between venous thromboembolism and low-quality nursing care. Pharmacological prophylaxis was highly used (90.9%), while the utilisation of mechanical prophylaxis and its proper use was relatively low. CONCLUSIONS: Chinese orthopaedic nurses demonstrated enthusiasm for venous thromboembolism and prophylaxis. Their knowledge needs to be improved, including the proper use of prophylaxis, identification of risk factors, signs and symptoms. Mechanical prophylaxis practice for VTE prevention after THA and TKA surgical procedures is not optimistic. Further studies should analyse the causes from multiple perspectives, including the availability of resources, the knowledge and attitude of doctors, nurses and patients. RELEVANCE TO CLINICAL PRACTICE: The findings from this study can be used to develop and implement interventions for venous thromboembolism after orthopaedic surgery.