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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Inhibitor of kappa B kinase interacting protein (IKBIP) has been reported to promote glioma progression, but its role in other cancers remains unclear. This study aimed to investigate the role of IKBIP and its underlying molecular mechanisms in ESCC. METHODS: The mRNA expression of IKBIP was analyzed using multiple cancer databases. Immunohistochemistry was performed to detect IKBIP protein expression in ESCC tissues and adjacent normal tissues, and KaplanâMeier survival and Cox regression analyses were carried out. The effects of IKBIP knockdown (or overexpression) on ESCC cells were detected by cell viability, cell migration, flow cytometry and Western blot assays. LY-294002 was used to validate the activation of the AKT signaling pathway by IKBIP. Finally, the role of IKBIP in ESCC was verified in a xenograft model. RESULTS: Both bioinformatics analysis and immunohistochemistry indicated that IKBIP expression in ESCC tissues was significantly increased and was associated with the prognosis of ESCC patients. In vitro experiments revealed that IKBIP knockdown significantly inhibited the proliferation and migration of ESCC cells, and induced cell apoptosis and G1/S phase arrest. Molecular mechanism results showed that the AKT signaling pathway was further activated after IKBIP overexpression, thereby increasing the proliferation and migration abilities of ESCC cells. In vivo study confirmed that IKBIP promoted the initiation and development of ESCC tumors in mice. CONCLUSIONS: IKBIP plays a tumor-promoting role in ESCC and may serve as a predictive biomarker and a potential therapeutic target for ESCC.
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Movimento Celular , Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Polissacarídeos , Infecção dos Ferimentos , Camundongos , Animais , Ácido Hialurônico/farmacologia , Fosfatidilinositol 3-Quinases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cicatrização , Anti-Infecciosos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , InflamaçãoRESUMO
Cp*Rh(III)-catalyzed chelation-assisted direct C-H bond functionalization of 1-(2-pyridyl)-2-pyridones with internal alkynes that can be controlled to give three different products in good yields has been realized. Depending on the reaction conditions, solvents and additives, the reaction pathway can be switched between alkenylation, alkenylation/directing group migration and rollover annulation. These reaction manifolds allow divergent access to a variety of valuable C6-alkenylated 1-(2-pyridyl)-2-pyridones, (Z)-6-(1,2-diaryl-2-(pyridin-2-yl)vinyl)pyridin-2(1H)-ones and 10H-pyrido[1,2-a][1,8]naphthyridin-10-ones from the same starting materials. These protocols exhibit excellent regio- and stereoselectivity, broad substrate scope, and good tolerance of functional groups. A combination of experimental and computational approaches have been employed to uncover the key mechanistic features of these reactions.
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Ródio , Alcinos , Catálise , PiridonasRESUMO
Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Tumor-associated macrophages (TAMs) inhepatocellularcarcinoma (HCC) play a prominent role in tumormicroenvironment by presenting M1(induced by IFN γ along with LPS) and M2(induced by IL-4 and IL13) polarization. Although TAMs are involved in tumor immune surveillance during the course of HCC, they contribute to tumour progression at different levels by inhibiting the anti-tumor immune response, promoting the generation of blood vessels and lymphatic vessels, and supporting the proliferation and survival of tumor cells. In this paper, the multiple functions of TAMs in HCC were reviewed to provide assistance for future researches about therapeutic approaches.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Macrófagos Associados a Tumor/imunologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Fígado/citologia , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Ischemia-reperfusion injury refers to organ damage caused by the previous insufficient supply of oxygen and nutrients and the involvement of metabolic by-products after blood flow is restored. Liver ischemia-reperfusion injury (IRI) has become a hot research in recent years, because it occurs in many clinical scenarios. After the introduction of liver transplantation and vascular control techniques in liver surgery, liver ischemia-reperfusion injury is considered to be an important factor affecting postoperative mortality and morbidity. As the largest immune organ in the human body, liver contain a lot of immune cells such as resident macrophages (Kupffer cells), dendritic cells, natural killer cells, and natural killer T cells which play a key role in ischemia-reperfusion injury. Among those, macrophage-mediated excessive inflammatory response is considered to be an important factor in liver ischemia-reperfusion injury. The prominent feature of liver injury is an increase in the number of macrophages in liver due to the infiltration of blood monocytes and differentiation into monocyte-derived macrophages. Liver macrophages can be divided into M1 macrophages which can promote inflammation progress and M2 macrophages that inhibit inflammation progress according to their different phenotypes and functions. Both of them can regulate liver aseptic inflammation, and play an important role in triggering, maintaining, and improving liver ischemia-reperfusion injury. This review summarizes studies of macrophage polarization on liver ischemia-reperfusion injury in recent years, to provide potential ideas for translation application in future clinical management.
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Falência Hepática/imunologia , Fígado/patologia , Macrófagos/imunologia , Complicações Pós-Operatórias/imunologia , Traumatismo por Reperfusão/imunologia , Animais , Modelos Animais de Doenças , Hepatectomia/efeitos adversos , Humanos , Fígado/citologia , Fígado/imunologia , Fígado/cirurgia , Falência Hepática/patologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/patologia , Traumatismo por Reperfusão/patologia , Ressuscitação/efeitos adversos , Ressuscitação/métodos , Choque Hemorrágico/complicações , Choque Hemorrágico/terapiaRESUMO
Developing efficient and cheap photocatalysts that are sensitive to indoor light is promising for the practical application of photocatalysis technology. Here, N-doped TiO2 photocatalyst with loaded Cu crystalline cocatalyst is synthesized by a simple one-pot method. The structure is confirmed by transmission electron microscopy and X-ray photoelectron spectroscopy analysis, which exhibit that Cu metal nanocrystalline is uniformly deposited on the surface of N-doped TiO2 material. UV-Vis absorption spectra illustrate that the modified samples possess favorable visible light absorption properties and suppressed-electron hole separation. The as-fabricated Cu-loaded N-TiO2 materials show high activity in photocatalytic decomposing isopropanol and inactivating E.coliunder the irradiation of a household white LED lamp. The developed synthetic strategy and photocatalytic materials reported here are promising for indoor environment purification.
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A highly enantioselective iridium- or ruthenium-catalyzed intermolecular reductive amination/asymmetric hydrogenation relay with 2-quinoline aldehydes and aromatic amines has been developed. A broad range of sterically tunable chiral N,N'-diaryl vicinal diamines were obtained in high yields (up to 95 %) with excellent enantioselectivity (up to >99 %â ee). The resulting chiral diamines could be readily transformed into sterically hindered chiral N-heterocyclic carbene (NHC) precursors, which are otherwise difficult to access. The usefulness of this synthetic approach was further demonstrated by the successful application of one of the chiral vicinal diamines and chiral NHC ligands in a transition-metal-catalyzed asymmetric Suzuki-Miyaura cross-coupling reaction and asymmetric ring-opening cross-metathesis, respectively.
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Two previously undescribed coumarins (1 and 2) were isolated from the root of Hansenia weberbaueriana which have been used to cure inflammatory diseases over thousands of years by Chinese. The structures of new findings were confirmed by comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR combined with chemical calculations. Compounds 1 and 2 exhibited potential anti-inflammatory properties by reducing the mRNA expression levels of TNF-α, IL-6 and IL-1ß in lipopolysaccharide (LPS)-induced RAW264.7 macrophages at a concentration of 15 µM.
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BACKGROUND: Mitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate ß-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. METHODS: We performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. FINDINGS: Our data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750â¯cm-1, 1128â¯cm-1 and 1585â¯cm-1 in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. INTERPRETATION: Our findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Análise Espectral Raman , Ácido 3-Hidroxibutírico/farmacologia , Mitocôndrias , Oxirredução , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.
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Matriz Extracelular , Hepatectomia , Hidrogéis , Células de Kupffer , Regeneração Hepática , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Camundongos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is essential for tumour metastasis. Neutrophil-associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung. METHOD: The lung metastasis models were constructed via treated cancer cells by tail vein injection into mice. And samples of lung were harvested at the indicated time to analyze tumor growth and immune cells in the microenvironment. Tumors and lung metastasis specimens were obtained via surgical operations for research purposes. Neutrophils were obtained from peripheral blood of patients with liver cancer or healthy donors (HD). RESULTS: Hepatocellular carcinoma cells reduce the secretion of histidine-rich glycoprotein (HRG), regulate the recruitment and activation of neutrophils in the metastatic microenvironment and promote the production of neutrophil extracellular traps (NETs), thereby promoting liver cancer lung metastasis. HRG binds to FCγR1 on the neutrophil membrane while inhibiting PI3K and NF-κB activation, thereby reducing IL-8 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8-MAPK and NF-κB pathway activation and ROS production, resulting in reduced NETs formation. CONCLUSIONS: Our study reveals that liver cancer regulates neutrophil recruitment and NETs formation in the metastatic microenvironment by reducing HRG secretion, thereby promoting tumour lung metastasis. The results of this study will contribute to the development of possible strategies for treating metastases.
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Armadilhas Extracelulares , Neoplasias Hepáticas , Neoplasias Pulmonares , Animais , Camundongos , Armadilhas Extracelulares/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , NF-kappa B/metabolismo , Microambiente TumoralRESUMO
Histidine-rich glycoprotein (HRGP) is a relatively less known glycoprotein, but it is abundant in plasma with a multidomain structure, which allows it to interact with many ligands and regulate various biological processes. HRGP ligands includes heme, Zn2+, thrombospondin, plasmin/plasminogen, heparin/heparan sulfate, fibrinogen, tropomyosin, IgG, FcγR, C1q. In many conditions, the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn2+ or exposure to low pH, such as sites of tissue injury or tumor growth. The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein, connecting with different ligands, especially on cell surfaces. Also, HRGP can selectively target IgG, which blocks the production of soluble immune complexes. The most common cell surface ligand of HRGP is heparan sulfate proteoglycan, and the interaction is also potentiated by elevated Zn2+ concentration and low pH. Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis, anti-tumor immune response, fibrinolysis and coagulation, soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells. In addition, it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly. This review outlines the molecular, structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.
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Purpose: The purpose of this study was to determine the relationship between psychological health and postoperative recovery and satisfaction in patients undergoing total joint arthroplasty (TJA). Methods: We prospectively enrolled patients undergoing TJA from July 2019 to December 2020. A psychological evaluation was conducted according to the Hospital Anxiety and Depression Scale (HADS). Based on the preoperative HADS scores, we grouped the patients into two groups: the symptomatic group and the asymptomatic group. Data on the Harris Hip Score (HHS), Knee Society Knee Scoring System (KSS), Forgotten Joint Score-12 (FJS-12), Short Form-12 (SF-12), and Numeric Rating Scale (NRS) for pain in these two groups were collected preoperatively and postoperatively. Then, these data were analyzed by Statistical Package for Social Sciences (SPSS) version 19. Results: The final cohort consisted of 80 patients. Patients undergoing TJA had significantly decreased HADS and NRS scores and improved HHS, KSS, SF-12, and FJS-12 scores (all p < 0.001). Compared with the symptomatic group, the asymptomatic group showed better postoperative recovery (p < 0.05), especially after total knee arthroplasty (TKA) (p < 0.05). Good postoperative recovery positively impacted the patients' postoperative psychological state. Conclusion: Finally, the psychological state can affect recovery after TJA, and successful TJA can help improve patients' psychological states, especially after TKA.
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Medicine treatments for bone-related diseases such as osteoporosis, bone metastasis, osteomyelitis, and osteolysis are often limited by insufficient drug concentration at the lesion sites owing to the low perfusion of bone tissue. A carrier that can deliver multiple bone destruction site-targeting drugs is required to address this limitation. Here, we reported a novel bone-targeting nano-drug delivery platform formed by the integration of zoledronate (ZOL) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The ZOL mixed zeolitic imidazolate framework (ZZF) nanoparticles were synthesized in water at room temperature (25 °C), where many biomacromolecules could maintain their activity. This allowed the ZZF nanoparticles to adapt the encapsulation ability and pH response release property from ZIF-8 and the excellent bone targeting performance of ZOL simultaneously. Considering the ease of preparation and biomacromolecule-friendly drug delivery of this nano platform, it may be useful in treating bone-related diseases.
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Estruturas Metalorgânicas , Zeolitas , Osso e Ossos , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/química , Zeolitas/química , Ácido ZoledrônicoRESUMO
The activation of oxygen (O2) under room condition is important for the utilization of air to perform oxidation. Here, we report a porous carbon-encapsulated MnO (MnO@C) derived from Mn metal-organic framework (MOF)grown in-situ on a graphite felt (GF) support. The MnO@C exhibits superior catalytic activity in an electric field-assisted catalytic oxidation system for the degradation of organic pollutants under room condition. The catalytic oxidation reaction applies a surface reaction pathway in which the surface-bound chemisorbed oxygen species are electro-oxidized and then involved in the oxidation of co-adsorbed organic pollutants. The abundant oxygen vacancies and oxygenated functional groups in MnO@C provide active sites for the chemisorption of O2, and its conductive mesoporous structure allows facile electrons and mass transfer. As a result, the MnO@C/GF catalyst displays quite high turnover frequency (TOF) value as 0.038 mg-TOC mg-MnO-1 min-1, which is 6.66 times higher than that of the MnO/GF catalyst prepared by impregnation method as a comparison. With the aid of + 1.0 V of positive electric field, the catalytic oxidation system exhibits extensive effectiveness in mineralizing a variety of dyes, pharmaceuticals, personal care products, and phenolic compounds under room condition with significantly enhanced biodegradability.
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Poluentes Ambientais , Grafite , Estruturas Metalorgânicas , Poluentes Químicos da Água , Catálise , Grafite/química , Oxirredução , Oxigênio/químicaRESUMO
Objectives: The hospitalization and mortality rate from COVID-19 appears to be higher in liver transplant recipients when compared with general populations. Vaccination is an effective strategy to reduce the risk during the COVID-19 pandemic. We aimed to evaluate COVID-19 vaccine hesitancy in liver transplant recipients. Methods: In April 2022, we conducted an online-based survey through WeChat platform to investigate the vaccination hesitancy among liver transplant recipients followed at Shanghai Renji Hospital and further explore possible influencing factors. Survey items included multiple choice, Likert-type rating scale and open-ended answers. Participants were classified as no hesitancy group and hesitancy group. Using univariate analysis, ROC curve analysis and multiple logistic regression to evaluate associations between baseline characteristics and COVID-19 vaccine hesitancy. Results: 449 liver transplant recipients participated in the survey with 299 (66.6%) of them being categorized as vaccine hesitancy. In no hesitancy group, 73 (48.7%) recipients had completed vaccination, while 77 (51.3%) were not yet but intended to be vaccinated. In contrast, 195 (65.2%) recipients in hesitancy group were hesitant to get vaccinated, while the remaining 104 (34.8%) refused. The most common side effect was injection arm pain (n = 9, 12.3%). The common reasons for vaccine willingness was trusted in the effectiveness of the vaccine and fear of contracting COVID-19. The most common reason for vaccination hesitancy is fear of side effects, and the most effective improvement was the support from the attending physician. Factors associated with vaccine hesitancy include female sex, influenza vaccination status, awareness of the importance and safety of vaccine, attitudes of doctors and others toward vaccine, medical worker source information of vaccine, relative/friend with medical background, total score of VHS (Vaccine Hesitancy Scale), accessibility of vaccine. Conclusion: For liver transplant recipients, COVID-19 vaccine is an important preventive measure. Identifying the factors influencing COVID-19 vaccine hesitancy is therefore critical to developing a promotion plan. Our study shows that more comprehensive vaccine knowledge popularization and relevant medical workers' training can effectively improve the acceptance of COVID-19 vaccine in this population.
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COVID-19 , Transplante de Fígado , Feminino , Humanos , Vacinas contra COVID-19 , Estudos Transversais , Pandemias , COVID-19/prevenção & controle , China , VacinaçãoRESUMO
Perioperative administration of tranexamic acid (TXA) is thought to be related to decreased postoperative implant-associated infection rates; however, the relationship remains unclear. We explored the inhibitory effect of TXA on infection both in vitro and in vivo. We investigated biofilm formation after TXA administration through different detection methods, all of which showed that TXA reduces biofilm formation in vitro and was further proven to be associated with decreased protein and polysaccharide contents in biofilms. We observed decreased biofilm on implants and decreased bacteria in the infection area with strengthened neutrophil accumulation in the mouse implant-associated infection model. Our results suggest that TXA protects against implant-associated infection by reducing biofilm formation in infected tissues.
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Antifibrinolíticos , Ácido Tranexâmico , Animais , Antifibrinolíticos/farmacologia , Biofilmes , Perda Sanguínea Cirúrgica , Humanos , Camundongos , Complicações Pós-Operatórias , Período Pós-Operatório , Ácido Tranexâmico/farmacologiaRESUMO
Bone metastasis (BM) is a solid tumor confined to narrow bone marrow cavities with a relatively poor blood supply and hypoxic environment, making conventional anticancer treatments difficult. In our study, we fabricated nanoparticles (NPs) based on zeolitic imidazolate framework-8 (ZIF-8) loaded with indocyanine green (ICG, a photodynamic agent) and cytochrome c (Cyt c, an anticancer protein) with a surface modified by zoledronate (ZOL, a bone-targeting moiety) and a polyvinyl pyrrolidone (PVP) coating to increase their stability. The ICG/Cyt c@ZZF-8 NPs were expected to have synergistic antitumor therapy and bone protection efficiency. The in vitro and in vivo experiments showed the bone-targeted and pH-sensitive ability of ICG/Cyt c@ZZF-8 NPs, which could be engulfed by tumor cells and release the cargos. Upon 780 nm laser irradiation, ICG produces cytotoxic reactive oxygen species (ROS, 1O2) that directly kill tumor cells, and Cyt c with catalase-like activity can induce programmed cell death and decompose H2O2 to O2, thus enhancing the PDT efficiency. The ZOL can further inhibit bone resorption. The ICG/Cyt c@ZZF-8 NPs showed improved antitumor and bone protection efficiency in a mouse model of BM. This study demonstrated a potential mode for the synergetic therapy of orthopedic diseases.
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Neoplasias Ósseas , Nanopartículas , Fotoquimioterapia , Zeolitas , Animais , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Citocromos c , Peróxido de Hidrogênio , Camundongos , Fármacos Fotossensibilizantes/farmacologiaRESUMO
Oxidative stress and excessive inflammatory responses are the two critical mechanisms of hepatic ischemia-reperfusion injury (HIRI) encountered in many clinical settings, including following hepatectomy and liver transplantation. Effective anti-inflammatory and anti-oxidative pharmacological interventions are urgently needed to counter HIRI. The present study showed that a biocompatible Prussian blue (PB) scavenger with reactive oxygen species (ROS) scavenging and anti-inflammatory properties might be used a promising treatment for HIRI. Following intravenous administration, PB scavenger was mainly distributed in the liver, where it showed excellent ability to alleviate apoptosis, tissue injury and organ dysfunction after HIRI. PB scavenger was found to protect liver tissue by scavenging ROS, reducing neutrophil infiltration and promoting macrophage M2 polarization. In addition, PB scavenger significantly reduced oxidative stress in primary hepatocytes, restoring cell viability under oxidative stress condition. PB scavenger effectively reduced lipopolysaccharide-stimulated inflammation in RAW 264.7 cells. These findings indicate that PB scavenger may be a potential therapeutic agent for the treatment of HIRI, providing an alternative treatment for ROS-associated and inflammatory liver diseases.
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Traumatismo por Reperfusão , Ferrocianetos , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controleRESUMO
Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.