RESUMO
The necessity to eliminate nickel (Ni) from wastewater stems from its environmental and health hazards. To enhance the Ni adsorption capacity, this research applied a copper sulfate-ammonia complex (tetraamminecopper (II) sulfate monohydrate, [Cu(NH3)4]SO4·H2O) as a modifying agent for a Phragmites australis-based activated carbon preparation. The physiochemical properties of powdered activated carbon (PAC) and a modified form ([Cu(NH3)4]-PAC) were examined by measuring their surface areas, analyzing their elemental composition, and using Boehm's titration method. Batch experiments were conducted to investigate the impact of various factors, such as Ni(II) concentration, contact time, pH, and ionic strength, on its substance adsorption capabilities. Additionally, the adsorption mechanisms of Ni(II) onto activated carbon were elucidated via Fourier-transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The findings indicated that modified activated carbon ([Cu(NH3)4]-PAC) exhibited a lower surface area and total volume than the original activated carbon (PAC). The modification of PAC enhanced its surface's relative oxygen and nitrogen content, indicating the incorporation of functional groups containing these elements. Furthermore, the modified activated carbon, [Cu(NH3)4]-PAC, exhibited superior adsorption capacity relative to unmodified PAC. Both adsorbents' adsorption behaviors conformed to the Langmuir model and the pseudo-second-order kinetics model. The Ni(II) removal efficiency of PAC and [Cu(NH3)4]-PAC diminished progressively with rising ionic strength. Modified activated carbon [Cu(NH3)4]-PAC demonstrated notable pH buffering and adaptability. The adsorption mechanism for Ni(II) on activated carbon involves surface complexation, cation exchange, and electrostatic interaction. This research presents a cost-efficient preparation technique for preparing activated carbon with enhanced Ni(II) removal capabilities from wastewater and elucidates its underlying adsorption mechanisms.
RESUMO
Nanoplastics (NPs), as an emerging contaminant, have usually been found charged in the environment, posing threats to aquatic animals. However, the underlying mechanisms governing the gut toxicity of differentially charged NPs to benthic insects are not well understood. In this study, the gut toxicity in larvae of Chironomus kiinensis exposed to negatively charged NPs (PS-COOH, 50 nm) and positively charged NPs (PS-NH2, 50 nm) at 0.1 and 1 g/kg was investigated through fluorescence imaging, histopathology, biochemical approaches, and 16S rRNA sequencing. The results showed that PS-NH2 caused more adverse effect on the larval growth performance and induced more severe oxidative stress, epithelial damage, and inflammatory responses in the gut than PS-COOH. The stronger impact caused by PS-NH2 was because the gut accumulated PS-NH2 more readily than PS-COOH for its negatively charged cell membrane. In addition, PS-NH2 were less agglomerated compared with PS-COOH, leading to an increased interaction with gut cell membranes and microbiota. Furthermore, alpha diversity and relative abundance of the keystone microbiota related to gut barrier and nutrient absorption were markedly lower exposed to PS-NH2 than PS-COOH, indirectly exacerbating stronger gut and growth damage. This study provides novel insights into the effect mechanisms underlying differentially charged NPs on benthic insects.
Assuntos
Chironomidae , Microbioma Gastrointestinal , Nanopartículas , Poluentes Químicos da Água , Animais , Poliestirenos/toxicidade , Microplásticos , RNA Ribossômico 16S/genética , Insetos , Larva/metabolismo , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
The repair of severe bone defects is still a formidable clinical challenge, requiring the implantation of bone grafts or bone substitute materials. The development of three-dimensional (3D) bioprinting has received considerable attention in bone tissue engineering over the past decade. However, 3D printing has a limitation. It only takes into account the original form of the printed scaffold, which is inanimate and static, and is not suitable for dynamic organisms. With the emergence of stimuli-responsive materials, four-dimensional (4D) printing has become the next-generation solution for biological tissue engineering. It combines the concept of time with three-dimensional printing. Over time, 4D-printed scaffolds change their appearance or function in response to environmental stimuli (physical, chemical, and biological). In conclusion, 4D printing is the change of the fourth dimension (time) in 3D printing, which provides unprecedented potential for bone tissue repair. In this review, we will discuss the latest research on shape memory materials and 4D printing in bone tissue repair.
Assuntos
Bioimpressão , Materiais Inteligentes , Engenharia Tecidual/métodos , Osso e Ossos , Bioengenharia , Impressão Tridimensional , Alicerces Teciduais/química , Materiais Biocompatíveis/químicaRESUMO
Bone tissue engineering (BTE) utilizes a special mix of scaffolds, cells, and bioactive factors to regulate the microenvironment of bone regeneration and form a three-dimensional bone simulation structure to regenerate bone tissue. Silk fibroin (SF) is perhaps the most encouraging material for BTE given its tunable mechanical properties, controllable biodegradability, and excellent biocompatibility. Numerous studies have confirmed the significance of SF for stimulating bone formation. In this review, we start by introducing the structure and characteristics of SF. After that, the immunological mechanism of SF for osteogenesis is summarized, and various forms of SF biomaterials and the latest development prospects of SF in BTE are emphatically introduced. Biomaterials based on SF have great potential in bone tissue engineering, and this review will serve as a resource for future design and research.
Assuntos
Materiais Biocompatíveis , Fibroínas , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Fibroínas/química , Alicerces Teciduais/química , Osso e Ossos , Osteogênese , Seda/químicaRESUMO
The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site is a vital constraint that affects the regenerative effect, which is closely related to the degree of a well-established vascular network. Hypoxia-inducible factor (HIF-1α), which is an essential transcription factor activated in hypoxic environments, plays a vital role in vascular network construction. HIF-1α, which plays a central role in regulating cartilage and bone formation, induces vascular invasion and differentiation of osteoprogenitor cells to promote and maintain extracellular matrix production by mediating the adaptive response of cells to changes in oxygen levels. However, the application of HIF-1α in bone tissue engineering is still controversial. As such, clarifying the function of HIF-1α in regulating the bone regeneration process is one of the urgent issues that need to be addressed. This review provides insight into the mechanisms of HIF-1α action in bone regeneration and related recent advances. It also describes current strategies for applying hypoxia induction and hypoxia mimicry in bone tissue engineering, providing theoretical support for the use of HIF-1α in establishing a novel and feasible bone repair strategy in clinical settings.
Assuntos
Regeneração Óssea , Osso e Ossos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Engenharia Tecidual , Humanos , Regeneração Óssea/genética , Regeneração Óssea/fisiologia , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , OxigênioRESUMO
BACKGROUND: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment. METHODS: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after 2 weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mouse lung tissues. RESULTS: CoQ10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1 mM, 6 h) in vitro. IPF mouse model was constructed through bleomycin (5 mg/kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects. CONCLUSION: CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation against bleomycin-induced IPF in mice.
Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Transplante de Células-Tronco/métodos , Ubiquinona/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Bleomicina/toxicidade , Células Cultivadas , Modelos Animais de Doenças , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ubiquinona/uso terapêuticoRESUMO
In recent years, bone tissue engineering (BTE), as a multidisciplinary field, has shown considerable promise in replacing traditional treatment modalities (i.e., autografts, allografts, and xenografts). Since bone is such a complex and dynamic structure, the construction of bone tissue composite materials has become an attractive strategy to guide bone growth and regeneration. Chitosan and its derivatives have been promising vehicles for BTE owing to their unique physical and chemical properties. With intrinsic physicochemical characteristics and closeness to the extracellular matrix of bones, chitosan-based composite scaffolds have been proved to be a promising candidate for providing successful bone regeneration and defect repair capacity. Advances in chitosan-based scaffolds for BTE have produced efficient and efficacious bio-properties via material structural design and different modifications. Efforts have been put into the modification of chitosan to overcome its limitations, including insolubility in water, faster depolymerization in the body, and blood incompatibility. Herein, we discuss the various modification methods of chitosan that expand its fields of application, which would pave the way for future applied research in biomedical innovation and regenerative medicine.
Assuntos
Quitosana , Engenharia Tecidual , Materiais Biocompatíveis/química , Regeneração Óssea , Osso e Ossos , Quitosana/química , Humanos , Alicerces Teciduais/químicaRESUMO
Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature's development, breeding, and homeostasis. Lately, some researchers have reported that both pathological hypoxia and environmental hypoxia might affect bone health. Adaptation to hypoxia is a pivotal cellular event in normal cell development and differentiation and in pathological settings such as ischemia. As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair. From this perspective, we summarized the role of HIF-1 and HIF-2 in signaling pathways implicated in bone development and skeletal repair and outlined the molecular mechanism of regulation of downstream growth factors and protein molecules such as VEGF, EPO, and so on. All of these present an opportunity for developing therapies for bone regeneration.
Assuntos
Osteogênese , Fator A de Crescimento do Endotélio Vascular , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Osteogênese/fisiologia , Oxigênio/metabolismo , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNPs) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then western blot analysis (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In an SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction, and WB, our results revealed that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. Collectively, these results indicated that BAS can be used as a promising compound for the treatment of human SCLC.
Assuntos
Acremonium/metabolismo , Produtos Biológicos/farmacologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide's biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/ß-tricalcium phosphate (ß-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.
Assuntos
Grafite , Osteogênese/efeitos dos fármacos , Óxidos , Peptídeos/química , Peptídeos/farmacologia , Engenharia Tecidual , Alicerces Teciduais , Animais , Regeneração Óssea , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Emulsões , Grafite/química , Nanoestruturas/química , Óxidos/química , Impressão Tridimensional , Ratos , Análise EspectralRESUMO
Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum lumen protein localized to the secretory pathway. As a Ca2t-binding protein of 45 kDa (Cab45)/Rcn/ER Ca2t-binding protein of 55 kDa (ERC45)/calumenin (CREC) family member, Rcn3 is reported to function as a chaperone protein involved in protein synthesis and secretion; however, the biological role of Rcn3 is largely unknown. The results presented here, for the first time, depict an indispensable physiological role of Rcn3 in perinatal lung maturation by using an Rcn3 gene knockout mouse model. These mutant mice die immediately at birth owing to atelectasis-induced neonatal respiratory distress, although these embryos are produced with grossly normal development. This respiratory distress results from a failure of functional maturation of alveolar epithelial type II cells during alveogenesis. This immaturity of type II cells is associated with a dramatic reduction in surfactant protein A and D, a disruption in surfactant phospholipid homeostasis, and a disorder in lamellar body. In vitro studies further show that Rcn3 deficiency blunts the secretion of surfactant proteins and phospholipids from lung epithelial cells, suggesting a decrease in availability of surfactants for their surface activity. Collectively, these observations indicate an essential role of Rcn3 in perinatal lung maturation and neonatal respiratory adaptation as well as shed additional light on the mechanism of neonatal respiratory distress syndrome development.
Assuntos
Células Epiteliais Alveolares/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Pulmão/metabolismo , Atelectasia Pulmonar/metabolismo , Síndrome do Desconforto Respiratório do Recém-Nascido/metabolismo , Insuficiência Respiratória/metabolismo , Adaptação Fisiológica , Células Epiteliais Alveolares/patologia , Animais , Proteínas de Ligação ao Cálcio/deficiência , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular , Regulação da Expressão Gênica no Desenvolvimento , Predisposição Genética para Doença , Homozigoto , Pulmão/embriologia , Pulmão/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfogênese , Mutação , Fenótipo , Fosfolipídeos/metabolismo , Atelectasia Pulmonar/embriologia , Atelectasia Pulmonar/genética , Atelectasia Pulmonar/fisiopatologia , Proteína A Associada a Surfactante Pulmonar/genética , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/genética , Proteína D Associada a Surfactante Pulmonar/metabolismo , Interferência de RNA , Síndrome do Desconforto Respiratório do Recém-Nascido/embriologia , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Insuficiência Respiratória/embriologia , Insuficiência Respiratória/genética , Insuficiência Respiratória/fisiopatologia , Transdução de Sinais , TransfecçãoRESUMO
Peripheral nerve injuries (PNIs) frequently occur due to various factors, including mechanical trauma such as accidents or tool-related incidents, as well as complications arising from diseases like tumor resection. These injuries frequently result in persistent numbness, impaired motor and sensory functions, neuropathic pain, or even paralysis, which can impose a significant financial burden on patients due to outcomes that often fall short of expectations. The most frequently employed clinical treatment for PNIs involves either direct sutures of the severed ends or bridging the proximal and distal stumps using autologous nerve grafts. However, autologous nerve transplantation may result in sensory and motor functional loss at the donor site, as well as neuroma formation and scarring. Transplantation of Schwann cells/Schwann cell-like cells has emerged as a promising cellular therapy to reconstruct the microenvironment and facilitate peripheral nerve regeneration. In this review, we summarize the role of Schwann cells and recent advances in Schwann cell therapy in peripheral nerve regeneration. We summarize current techniques used in cell therapy, including cell injection, 3D-printed scaffolds for cell delivery, cell encapsulation techniques, as well as the cell types employed in experiments, experimental models, and research findings. At the end of the paper, we summarize the challenges and advantages of various cells (including ESCs, iPSCs, and BMSCs) in clinical cell therapy. Our goal is to provide the theoretical and experimental basis for future treatments targeting peripheral nerves, highlighting the potential of cell therapy and tissue engineering as invaluable resources for promoting nerve regeneration.
Assuntos
Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Células de Schwann , Células de Schwann/fisiologia , Humanos , Animais , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Nervos Periféricos/fisiologiaRESUMO
Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.
Assuntos
Ácidos Borônicos , Diabetes Mellitus Experimental , Glucose , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Ácidos Borônicos/química , Glucose/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Agulhas , Insulina/administração & dosagem , Camundongos , Quitosana/química , Álcool de Polivinil/química , Ratos , Ácido Hialurônico/química , Masculino , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Sistemas de Liberação de Medicamentos , Ratos Sprague-Dawley , Humanos , Hidrogéis/químicaRESUMO
Immune cells are pivotal in the dynamic interplay between hypoxia and inflammation. During hypoxic conditions, HIF-1α, a crucial transcription factor, facilitates the adaptation of immune cells to the hypoxic micro-environment. This adaptation includes regulating immune cell metabolism, significantly impacting inflammation development. Strategies for anti-inflammatory and hypoxic relief have been proposed, aiming to disrupt the hypoxia-inflammation nexus. Research extensively focuses on anti-inflammatory agents and materials that target immune cells. These primarily mitigate hypoxic inflammation by encouraging M2-macrophage polarization, restraining neutrophil proliferation and infiltration, and maintaining Treg/TH17 balance. Additionally, oxygen-releasing nano-materials play a significant role. By alleviating hypoxia and clearing reactive oxygen species (ROS), these nano-materials indirectly influence immune cell functions. This paper delves into the response of immune cells under hypoxic conditions and the resultant effects on inflammation. It provides a comprehensive overview of various therapies targeting specific immune cells for anti-inflammatory purposes and explores nano-materials that either carry or generate oxygen to alleviate anoxic micro-environments.
Assuntos
Hipóxia , Inflamação , Humanos , Inflamação/tratamento farmacológico , Oxigênio , Ativação de Macrófagos , Anti-Inflamatórios/farmacologiaRESUMO
The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.
Assuntos
Antibacterianos , Biofilmes , NF-kappa B , Nanopartículas , Percepção de Quorum , Cicatrização , Animais , Humanos , Camundongos , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Flavanonas/química , Flavanonas/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Indóis/química , Indóis/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Nanopartículas/química , Nanopartículas/uso terapêutico , NF-kappa B/metabolismo , Polímeros/química , Polímeros/farmacologia , Percepção de Quorum/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
To identify a replacement strategy for bronchial thermoplasty (BT) with non-invasive and free-of-severe side effect is urgently needed in the clinic for severe asthma treatment. In this study, PLGA-PEG@ICG@TRPV1 pAb (PIT) photothermal nanoparticles targeting bronchial TRPV1 were designed for photothermal therapy (PTT) against severe murine asthma induced by ovalbumin and lipopolysaccharide. PIT was formulated with a polyethylene glycol (PEG)-grafted poly (lactic-co-glycolic) acid (PLGA) coating as a skeleton structure to encapsulate indocyanine green (ICG) and was conjugated to the polyclonal antibody against transient receptor potential vanilloid 1 (TRPV1 pAb). The results revealed that PIT held good druggability due to its electronegativity and small diameter. PIT demonstrated great photothermal effects both in vivo and in vitro and exhibited good ability to target TRPV1 in vitro because of its selective cell uptake and specific cell toxicity toward TRPV1-overexpressing cells. The PIT treatment effectively reduced asthma symptoms in mice. This is evident from improvements in expiratory airflow limitation, significant decreases in inflammatory cell infiltration in the airways, and increases in goblet cell and columnar epithelial cell proliferation. In conclusion, PIT alleviates severe murine asthma symptoms through a combination of TRPV1 targeting and photothermal effects.
Assuntos
Antineoplásicos , Asma , Nanopartículas , Animais , Camundongos , Verde de Indocianina , Fototerapia/métodos , Ovalbumina , Lipopolissacarídeos , Nanopartículas/química , Polietilenoglicóis/química , Asma/tratamento farmacológico , Linhagem Celular Tumoral , Canais de Cátion TRPVRESUMO
Early reconstruction of the vascular network is a prerequisite to the effective treatment of substantial bone defects. Traditional 3D printed tissue engineering scaffolds designed to repair large bone defects do not effectively regenerate the vascular network, and rely only on the porous structure within the scaffold for nutrient transfer and metabolic waste removal. This leads to delayed bone restoration and hence functional recovery. Therefore, strategies for generation scaffolds with the capacity to efficiently regenerate vascularization should be developed. This study loads roxarestat (RD), which can stabilize HIF-1α expression in a normoxic environment, onto the mesopore polydopamine nanoparticles (MPDA@RD) to enhance the reconstruction of vascular network in large bone defects. Subsequently, MPDA@RD is mixed with GelMA/HA hydrogel bioink to fabricate a multifunctional hydrogel scaffold (GHM@RD) through 3D printing. In vitro results show that the GHM@RD scaffolds achieve good angiogenic-osteogenic coupling by activating the PI3K/AKT/HSP90 pathway in BMSCs and the PI3K/AKT/HIF-1α pathway in HUVECs under mild thermotherapy. In vivo experiments reveal that RD and mild hyperthermia synergistically induce early vascularization and bone regeneration of critical bone defects. In conclusion, the designed GHM@RD drug delivery scaffold with mild hyperthermia holds great therapeutic value for future treatment of large bone defects.
RESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.
Assuntos
Genoma Viral , Filogenia , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Vírus da Síndrome Respiratória e Reprodutiva Suína/classificação , China , Síndrome Respiratória e Reprodutiva Suína/virologia , Síndrome Respiratória e Reprodutiva Suína/patologia , Virulência , Evolução MolecularRESUMO
With the global reduction actions of greenhouse gas (GHG) emissions, environmental facilities, including sewage treatment plants (STPs), need to reduce pollutants while minimizing GHG emissions. Therefore, more and more publications revealed the formation mechanism of GHGs in STPs and committed to finding better reduction schemes. From the perspective of bibliometrics, this study used CiteSpace to conduct quantitative and visual analysis based on 1,543 publications retrieved from Web of Science between 2000 and 2021 around the world. We have systematically evaluated the structure, development trend, hot spots, and research frontier in the field of GHG emissions from STPs and compared with the contents of top journals to verify the scientificity of the analysis. The results show that the number of publications has increased year by year, and the networks of authors and institutions show a strong correlation. Among them, the clusters of nitrous oxide, anaerobic digestion, and life cycle assessment (LCA) started earlier and received extensive attention, which derived other clusters in the research process. With the development of the field, researchers have gradually changed from single water treatment facilities to multi-carriers that can realize energy regeneration and utilization simultaneously. Accordingly, the GHG reduction of STPs through energy regeneration and resource recovery has become a hot point and frontier direction, which also challenges the breakthroughs in relevant technologies. Furthermore, it provides scientific support for the formulation of relevant incentive policies and economic subsidy systems, so as to alleviate the pressure of global warming and realize the sustainable development of STPs concurrently.
Assuntos
Gases de Efeito Estufa , Esgotos , Efeito Estufa , Óxido Nitroso/análise , Bibliometria , Metano/análiseRESUMO
Early detection of Sepsis is crucial for improving patient outcomes, as it is a significant public health concern that results in substantial morbidity and mortality. However, despite the widespread use of the Sequential Organ Failure Assessment (SOFA) in clinical settings to identify sepsis, obtaining sufficient physiological data before onset remains challenging, limiting early detection of sepsis. To address this challenge, we propose an interpretable machine learning model, ITFG (Interpretable Tree-based Feature Generation), that leverages potential correlations between features based on existing knowledge to identify sepsis within six hours of onset using valuable and continuous physiological measures. Furthermore, we introduce a Semi-supervised Attention-based Conditional Transfer Learning (SAC-TL) framework to enhance the model's generality and enable it to be used for early warning of sepsis in the target domain with less information from the source domain. Our proposed approaches effectively address the problem of systematic feature sparsity and missing data, while also being practical for different degrees of generalizability. We evaluated our proposed approaches on open datasets, MIMIC and PhysioNet, obtaining AUC of 97.98% and 86.21%, respectively, demonstrating their effectiveness in different data environments and achieving the best early detection results.