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By establishing an in vitro model of D-Gal-induced brain neuronal cell (HT-22) senescence, it was found that TAX treatment significantly increased the activities of SOD and GSH, while decreasing MDA levels in aging HT-22 cells, indicating that TAX effectively restored the total antioxidant capacity and antioxidant enzyme activity of aging HT-22 cells induced by D-Gal, and attenuated cellular oxidative stress injury. In addition, taxifolin could also protect HT-22 cells from aging by up-regulating SIRT1 while reducing the expression of Ac-p53, indicating that TAX may be an active substance that can effectively delay cell aging.
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Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/ß receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Camundongos Endogâmicos C57BL , RNA Circular , Infecção por Zika virus , Zika virus , Animais , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/imunologia , Zika virus/imunologia , Zika virus/genética , Camundongos , Anticorpos Neutralizantes/imunologia , RNA Circular/genética , RNA Circular/imunologia , Anticorpos Antivirais/imunologia , Vírus da Dengue/imunologia , Vírus da Dengue/genética , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Humanos , Camundongos Knockout , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/genética , Dengue/prevenção & controle , Dengue/imunologia , Feminino , Anticorpos Facilitadores , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/imunologia , Receptor de Interferon alfa e beta/genética , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genéticaRESUMO
Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.
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Alginatos , Quitosana , Lipossomos , Florizina , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Cicatrização/efeitos dos fármacos , Lipossomos/química , Animais , Florizina/farmacologia , Florizina/química , Hidrogéis/química , Hidrogéis/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Oxirredução/efeitos dos fármacos , Humanos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Liberação Controlada de Fármacos , CamundongosRESUMO
Sulfation of polysaccharides can affect their biological activity by introducing sulfate groups. Skin burns occur regularly and have a great impact on normal survival. In this study, sulfated arabinogalactan (SAG) was prepared by sulfation, and polyvinyl alcohol (PVA) was used to prepare hydrogels for the treatment of scalded skin in mouse. The results show that the main chain of SAG consists of â3-ß-D-Galactose (Gal)-(1, â3, 6)-ß-D-Gal-(1 and â4)-ß-d-Glucose (Glc)-(1. The chain is a neutral polysaccharide composed of T-ß-L-Arabinose (Araf)-(1â, with a molecular weight of 17.9 kDa. At the same time, PVA + SAG hydrogel can promote the scald repair of mouse skin by promoting collagen deposition and angiogenesis, and regulating the TLR4/MyD88/NF-κB signaling pathway. Interestingly, the effect of SAG on promoting the repair of scald wounds is enhanced after AG is derivatized by sulfation. Therefore, the preparation of SAG by sulfation can promote scald repair, and has great application potential in the field of food and medicine.
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Queimaduras , Modelos Animais de Doenças , Galactanos , Hidrogéis , Cicatrização , Animais , Galactanos/química , Galactanos/farmacologia , Cicatrização/efeitos dos fármacos , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Queimaduras/tratamento farmacológico , Sulfatos/química , Álcool de Polivinil/química , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Colágeno/metabolismoRESUMO
The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.
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Patients who receive thoracic radiotherapy may suffer from radiation-induced lung injury, but the treatment options are limited as the underlying mechanisms are unclear. Using a mouse model of right thorax irradiation with fractionated doses of X-rays for three consecutive days (8 Gy/per day), this study found that the thoracic irradiation (Th-IR) induced tissue injury with aberrant infiltration of macrophages, and it significantly increased the secretion of TNF-α, IL-1ß, IL-6, TGF-ß1 and serum amyloid A (SAA) in mice. Interestingly, SAA could activate macrophages and then induce epithelial-mesenchymal transition (EMT) of lung epithelial cells and fibrosis progression in lung tissue. Mechanistically, SAA enhanced the transient binding of FPR2 to Rac1 protein and further activated NF-κB signaling pathway in macrophages. Inhibition of FPR2 significantly reduced pulmonary fibrosis induced by SAA administration in mice. In addition, cimetidine could reduce the level of SAA release after irradiation and attenuate the lung injury induced by SAA or Th-IR. In conclusion, our results demonstrated that SAA activated macrophages via FPR2/Rac1/NF-κB pathway and might contribute to the Th-IR induced lung injury, which may provide a new strategy to attenuate radiation-induced adverse effects during radiotherapy.
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Lesão Pulmonar , Macrófagos , NF-kappa B , Receptores de Formil Peptídeo , Proteína Amiloide A Sérica , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP , Animais , Proteína Amiloide A Sérica/metabolismo , Camundongos , NF-kappa B/metabolismo , Receptores de Formil Peptídeo/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Camundongos Endogâmicos C57BL , Masculino , Receptores de Lipoxinas/metabolismo , Transição Epitelial-Mesenquimal/efeitos da radiação , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , NeuropeptídeosRESUMO
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
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Quercetina , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Quercetina/química , Humanos , Animais , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Hepatopatias/prevenção & controle , Hepatopatias/patologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/lesões , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/químicaRESUMO
RATIONALE AND OBJECTIVES: This study aimed to evaluate the safety and effectiveness of transbrachial access (TBA) and transradial access (TRA) compared to transfemoral access (TFA) for large-bore neuro stenting (≥7 F). METHODS: From January 2019 to January 2024, 4752 patients received large-bore neuro stenting in our center. The primary outcomes were procedural metrics. Safety outcomes were significant access site complications, including substantial hematoma, pseudoaneurysm, artery occlusion, and complications requiring treatment (medicine, intervention, or surgery). After propensity score matching with a ratio of 1:1:2 (TBA: TRA: TFA), adjusting for age, gender, aortic arch type, and neuro stenting as covariates, outcomes were compared between groups. RESULTS: 46 TBA, 46 TRA and 92 TFA patients were enrolled. The mean age was 67.8 ± 11.2 years, comprising 127 (69.0%) carotid artery stenting and 57 (31.0%) vertebral artery stenting. The rates of technical success (TBA: 100%, TRA: 95.7%, TFA: 100%) and significant access site complications (TBA: 4.3%, TRA: 6.5%, TFA: 1.1%) were comparable between the groups (P > 0.05). Compared to TFA, the TRA cohort exhibited significant delays in angiosuite arrival to puncture time (14 vs. 8 min, P = 0.039), puncture to angiography completion time (19 vs. 11 min, P = 0.027), and procedural duration (42 vs. 29 min, P = 0.031). There were no substantial differences in procedural time metrics between TBA (10, 14, and 31 min, respectively) and TFA. CONCLUSION: TBA and TRA as the primary access for large-bore neuro stenting are safe and effective. Procedural delays in TRA may favor TBA as the first-line alternative access to TFA.
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Different aminated starch (AS) [EEAS (introducing ethylenediamine into starch using cross-linking-etherification-amination method (CEA)), EPAS (introducing o-phenylenediamine using CEA), OEAS (introducing ethylenediamine using cross-linking-oxidation-amination method (COA)), and OPAS (introducing o-phenylenediamine using COA)] were synthesized. The AS-phenolic acids [gallic acid (GA), syringic acid (SA), and vanillic acid (VA)] conjugates were prepared by laccase-catalyzed reaction. The grafting efficiency of EEAS on GA, SA, and VA was 36.59%, 69.71%, and 68.85%, respectively. SA reduced the maximum depolymerization rate of EEAS. The relative crystallinity of EEAS and EPAS grafted phenolic acid increased, and their particles showed severe breakage in appearance. OEAS-phenolic acid conjugates lost its granular structure and behaved as flakes and lumps, while the surface of OPAS-phenolic acid conjugates remained smooth after grafting phenolic acid. GA increased the DPPH· scavenging efficiency of EEAS from 16.12% to 79.92%. The increased antioxidant capacity of the conjugates suggested that AS-phenolic acids conjugates have high potential for applications.
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Antioxidantes , Hidroxibenzoatos , Amido , Antioxidantes/química , Hidroxibenzoatos/química , Amido/química , Aminação , Estrutura MolecularRESUMO
Near-infrared (NIR) light powdered CO2 photoreduction reaction is generally restricted to the separation efficiency of photogenerated carriers and the supply of active hydrogen (*H). Herein, the study reports a retrofitting hydrogenated MoO3-x (H-MoO3-x) nanosheet photocatalysts with Ru single atom substitution (Ru@H-MoO3-x) fabricated by one-step solvothermal method. Experiments together with theoretical calculations demonstrate that the synergistic effect of Ru substitution and oxygen vacancy can not only inhibit the recombination of photogenerated carriers, but also facilitate the CO2 adsorption/activation as well as the supply of *H. Compared with H-MoO3-x, the Ru@H-MoO3-x exhibit more favorable formation of *CHO in the process of *CO conversion due to the fast *H generation on electron-rich Ru sites and transfer to *CO intermediates, leading to the preferential photoreduction of CO2 to CH4 with high selectivity. The optimized Ru@H-MoO3-x exhibits a superior CO2 photoreduction activity with CH4 evolution rate of 111.6 and 39.0 µmol gcatalyst -1 under full spectrum and NIR light irradiation, respectively, which is 8.8 and 15.0 times much higher than that of H-MoO3-x. This work provides an in-depth understanding at the atomic level on the design of NIR responsive photocatalyst for achieving the goal of carbon neutrality.
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Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.
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OBJECTIVE: To propose a convolutional neural network (EmbNet) for automatic pulmonary embolism detection on computed tomography pulmonary angiogram (CTPA) scans and to assess its diagnostic performance. METHODS: 305 consecutive CTPA scans between January 2019 and December 2021 were enrolled in this study (142 for training, 163 for internal validation), and 250 CTPA scans from a public dataset were used for external validation. The framework comprised a preprocessing step to segment the pulmonary vessels and the EmbNet to detect emboli. Emboli were divided into three location-based subgroups for detailed evaluation: central arteries, lobar branches, and peripheral regions. Ground truth was established by three radiologists. RESULTS: The EmbNet's per-scan level sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 90.9%, 75.4%, 48.4%, and 97.0% (internal validation) and 88.0%, 70.5%, 42.7%, and 95.9% (external validation). At the per-embolus level, the overall sensitivity and PPV of the EmbNet were 86.0% and 61.3% (internal validation), and 83.5% and 57.5% (external validation). The sensitivity and PPV of central emboli were 89.7% and 52.0% (internal validation), and 94.4% and 43.0% (external validation); of lobar emboli were 95.2% and 76.9% (internal validation), and 93.5% and 72.5% (external validation); and of peripheral emboli were 82.6% and 61.7% (internal validation), and 80.2% and 59.4% (external validation). The average false positive rate was 0.45 false emboli per scan (internal validation) and 0.69 false emboli per scan (external validation). CONCLUSION: The EmbNet provides high sensitivity across embolus locations, suggesting its potential utility for initial screening in clinical practice.
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Angiografia por Tomografia Computadorizada , Redes Neurais de Computação , Embolia Pulmonar , Sensibilidade e Especificidade , Embolia Pulmonar/diagnóstico por imagem , Humanos , Angiografia por Tomografia Computadorizada/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Estudos Retrospectivos , Idoso de 80 Anos ou maisRESUMO
Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-ß1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.
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Quitosana , Flavonóis , Lipossomos , Animais , Quitosana/química , Quitosana/farmacologia , Lipossomos/química , Flavonóis/farmacologia , Flavonóis/administração & dosagem , Camundongos , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/lesões , Fígado/patologia , Antioxidantes/farmacologia , Antioxidantes/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , HumanosRESUMO
To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.
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Proliferação de Células , Quitosana , Hidrogéis , Lipossomos , Osteoblastos , Quercetina , Quercetina/análogos & derivados , Crânio , Via de Sinalização Wnt , Animais , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Quercetina/farmacologia , Quercetina/química , Lipossomos/química , Via de Sinalização Wnt/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Crânio/efeitos dos fármacos , Crânio/patologia , Crânio/metabolismo , Ratos , Regeneração Óssea/efeitos dos fármacos , Ratos Sprague-Dawley , Osteogênese/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Diferenciação Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Simulação de Acoplamento MolecularRESUMO
Bacterial infection, hyperinflammation and hypoxia, which can lead to amputation in severe cases, are frequently observed in diabetic wounds, and this has been a critical issue facing the repair of chronic skin injuries. In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ± 2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO2), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H2O2) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H2O2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted antimicrobial and anti-oxidative stress properties, and the bacterial inhibition rate against Staphylococcus aureus and Escherichia coli reached 90 %. In vivo experiments have shown that PTH hydrogel is able to treat diabetic skin repair by inhibiting the expression of inflammation-related proteins and promoting epidermal neogenesis, angiogenesis and collagen deposition.
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Alginatos , Quitosana , Hidrogéis , Álcool de Polivinil , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Alginatos/química , Alginatos/farmacologia , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Animais , Álcool de Polivinil/química , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Quercetina/farmacologia , Quercetina/química , Quercetina/análogos & derivados , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Escherichia coli/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , CamundongosRESUMO
The involvement of secreted phospholipase A2s in respiratory diseases, such as asthma and respiratory viral infections, is well-established. However, the specific role of secreted phospholipase A2 group IIE (PLA2G2E) during influenza virus infection remains unexplored. Here, we investigated the role of PLA2G2E during H1N1 influenza virus infection using a targeted mouse model lacking Pla2g2e gene (Pla2g2e-/-). Our findings demonstrated that Pla2g2e-/- mice had significantly lower survival rates and higher viral loads in lungs compared to wild-type mice following influenza virus infection. While Pla2g2e-/- mice displayed comparable innate and humoral immune responses to influenza virus challenge, the animals showed impaired influenza-specific cellular immunity and reduced T cell-mediated cytotoxicity. This indicates that PLA2G2E is involved in regulating specific T cell responses during influenza virus infection. Furthermore, transgenic mice expressing the human PLA2G2E gene exhibited resistance to influenza virus infection along with enhanced influenza-specific cellular immunity and T cell-mediated cytotoxicity. Pla2g2e deficiency resulted in perturbation of lipid mediators in the lung and T cells, potentially contributing to its impact on the anti-influenza immune response. Taken together, these findings suggest that targeting PLA2G2E could hold potential as a therapeutic strategy for managing influenza virus infections.IMPORTANCEThe influenza virus is a highly transmissible respiratory pathogen that continues to pose a significant public health concern. It effectively evades humoral immune protection conferred by vaccines and natural infection due to its continuous viral evolution through the genetic processes of antigenic drift and shift. Recognition of conserved non-mutable viral epitopes by T cells may provide broad immunity against influenza virus. In this study, we have demonstrated that phospholipase A2 group IIE (PLA2G2E) plays a crucial role in protecting against influenza virus infection through the regulation of T cell responses, while not affecting innate and humoral immune responses. Targeting PLA2G2E could therefore represent a potential therapeutic strategy for managing influenza virus infection.
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Vírus da Influenza A Subtipo H1N1 , Pulmão , Infecções por Orthomyxoviridae , Animais , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vírus da Influenza A Subtipo H1N1/imunologia , Pulmão/virologia , Pulmão/imunologia , Pulmão/patologia , Humanos , Fosfolipases A2 do Grupo II/genética , Fosfolipases A2 do Grupo II/imunologia , Linfócitos T/imunologia , Camundongos Knockout , Imunidade Celular , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Carga Viral , Modelos Animais de Doenças , Imunidade Humoral , Imunidade Inata , Influenza Humana/imunologia , Influenza Humana/virologia , FemininoRESUMO
Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.
Assuntos
Hipertermia Induzida , Indóis , Nanopartículas , Neoplasias Ovarianas , Polímeros , Quercetina/análogos & derivados , Humanos , Feminino , Fototerapia/métodos , Hipertermia Induzida/métodos , Neoplasias Ovarianas/tratamento farmacológico , Doxorrubicina/farmacologiaRESUMO
Abscisic acid (ABA) is a plant hormone with various biological activities. Aging is a natural process accompanied by cognitive and physiological decline, and aging and its associated diseases pose a serious threat to public health, but its mechanisms remain insufficient. Therefore, the purpose of this study was to investigate the ameliorative effects of ABA on d-galactose (D-Gal)-induced aging in mice and to delve into its molecular mechanisms. Aging model was es-tablished by theintraperitoneal injection of D-Gal. We evaluated the oxidative stress by measuring superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) levels in serum. Proteins content in brain were determined by Western blot. D-Gal-induced brain damage was monitored by measuring the levels of acetylcholinesterase (AChE) content and hematoxylin-eosin staining (H&E). To evaluate the effects of ABA on aging, we measured the gut microbiota. The results demonstrated that ABA increased SOD, CAT and AChE, decreased MDA level. H&E staining showed that ABA could improve D-Gal-induced damage. In addition, ABA regulated the B-cell-lymphoma-2 (BCL-2) family and Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling pathway, while further regulating the acetylation of p53 protein by modulating the AMPK pathway and activating SIRT1 protein, thereby inhibiting the apoptosis of brain neurons and thus regulating the aging process. Interestingly, ABA improved the ratio of intestinal bacteria involved in regulating multiple metabolic pathways in the aging process, such as Bacteroides, Firmicutes, Lactobacillus and Ak-kermansia. In conclusion, the present study suggests that ABA may be responsible for improving and delaying the aging process by enhancing antioxidant activity, anti-apoptosis and regulating intestinal flora.
RESUMO
Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.
RESUMO
Due to impaired immune function, diabetic wounds are highly susceptible to the development of excessive inflammatory responses and prolonged recurrent bacterial infections that impede diabetic wound healing. Therefore, it is necessary to design and develop a wound dressing that controls bacterial infection and inhibits excessive inflammatory response. In this study, hyaluronic acid (HA) was modified using dopamine (DA). Subsequently, cordycepin (COR) was loaded into dopamine-modified hyaluronic acid (OHDA)/gelatin (GEL) nanofiber wound dressing by electrostatic spinning technique. The constructed COR/OHDA/GEL nanofiber membrane has good thermal stability, hydrophilicity, and air permeability. In vitro experiments showed that the obtained COR/OHDA/GEL nanofiber membranes had good antimicrobial efficacy (S. aureus: 95.60 ± 0.99 %, E. coli: 71.17 ± 6.87 %), antioxidant activity (>90 %), and biocompatibility. In vivo experiments showed that COR/OHDA/GEL nanofiber membranes could promote wound tissue remodeling, collagen deposition, and granulation tissue regeneration. Western blot experiments showed that COR/OHDA/GEL nanofibrous membranes could inhibit the excessive inflammatory response of wounds through the TLR4/NF-κB signaling pathway. Therefore, COR/OHDA/GEL nanofiber membranes could promote diabetic wound healing by modulating the inflammatory response. The results showed that the designed nanofiber wound dressing is expected to provide a new strategy for treating chronic wounds.