RESUMO
IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.
Assuntos
Coinfecção , Proteínas de Ligação a DNA , Hepacivirus , Vírus da Hepatite B , Hepatite B , Hepatite C , Imunidade Inata , Humanos , Coinfecção/imunologia , Coinfecção/virologia , Proteínas de Ligação a DNA/metabolismo , Hepacivirus/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite C/virologia , Inflamassomos/metabolismo , Interferon gama/imunologiaRESUMO
The maintenance of nuclear shape is essential for cellular homeostasis and disruptions in this process have been linked to various pathological conditions, including cancer, laminopathies, and aging. Despite the significance of nuclear shape, the precise molecular mechanisms controlling it are not fully understood. In this study, we have identified the YEATS domain-containing protein 4 (GAS41) as a previously unidentified factor involved in regulating nuclear morphology. Genetic ablation of GAS41 in colorectal cancer cells resulted in significant abnormalities in nuclear shape and inhibited cancer cell proliferation both in vitro and in vivo. Restoration experiments revealed that wild-type GAS41, but not a YEATS domain mutant devoid of histone H3 lysine 27 acetylation or crotonylation (H3K27ac/cr) binding, rescued the aberrant nuclear phenotypes in GAS41-deficient cells, highlighting the importance of GAS41's binding to H3K27ac/cr in nuclear shape regulation. Further experiments showed that GAS41 interacts with H3K27ac/cr to regulate the expression of key nuclear shape regulators, including LMNB1, LMNB2, SYNE4, and LEMD2. Mechanistically, GAS41 recruited BRD2 and the Mediator complex to gene loci of these regulators, promoting their transcriptional activation. Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.
Assuntos
Núcleo Celular , Neoplasias Colorretais , Fatores de Transcrição , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Núcleo Celular/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Linhagem Celular Tumoral , Proliferação de Células , Camundongos , Histonas/metabolismo , Camundongos Nus , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Células HCT116 , Proteínas que Contêm BromodomínioRESUMO
The electrocatalytic nitrate reduction reaction (NO3--ERR) to ammonia (NH3) is a promising strategy for NH3 production. Cu-based nanomaterials have been regarded as a kind of effective NO3--ERR catalysts. In this work, high-quality hollow Cu2O nanocubes (Cu2O h-NCs) are facilely synthesized by a simple one-step reduction method. The as-prepared Cu2O h-NCs reveal high selectivity and activity for NO3--ERR, which is ascribed to abundant oxygen vacancies, high surface area, hollow architecture, low mass transfer resistance, and strong adsorbing ability toward NO3-. In fact, Cu2O h-NCs can achieve a Faradic efficiency of 92.9% and an NH3 yield of 56.2 mg h-1 mgcat-1 for NH3 production at -0.85 V (vs RHE) potential, which exceeds those of other transition-metal-based NO3--ERR electrocatalysts.
RESUMO
Acute myocardial infarction (MI) induces a sterile inflammatory response that may result in poor cardiac remodeling and dysfunction. Despite the progress in anti-cytokine biologics, anti-inflammation therapy of MI remains unsatisfactory, due largely to the lack of targeting and the complexity of cytokine interactions. Based on the nature of inflammatory chemotaxis and the cytokine-binding properties of neutrophils, we fabricated biomimetic nanoparticles for targeted and broad-spectrum anti-inflammation therapy of MI. By fusing neutrophil membranes with conventional liposomes, we fabricated biomimetic liposomes (Neu-LPs) that inherited the surface antigens of the source cells, making them ideal decoys of neutrophil-targeted biological molecules. Based on their abundant chemokine and cytokine membrane receptors, Neu-LPs targeted infarcted hearts, neutralized proinflammatory cytokines, and thus suppressed intense inflammation and regulated the immune microenvironment. Consequently, Neu-LPs showed significant therapeutic efficacy by providing cardiac protection and promoting angiogenesis in a mouse model of myocardial ischemia-reperfusion. Therefore, Neu-LPs have high clinical translation potential and could be developed as an anti-inflammatory agent to remove broad-spectrum inflammatory cytokines during MI and other neutrophil-involved diseases.
Assuntos
Citocinas , Neutrófilos , Animais , Anti-Inflamatórios , Biomimética , Modelos Animais de Doenças , Lipopolissacarídeos , Lipossomos , CamundongosRESUMO
Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia-reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia-reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value.
Assuntos
Lipossomos , Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Preparações de Ação RetardadaRESUMO
PURPOSE: We performed a novel anatomical and radiological investigation to understand the structure of nasolacrimal duct (NLD) and to provide data to help surgeons locate the openings of NLD efficiently based on landmarks. MATERIALS AND METHODS: We examined the NLD region using computed tomography images of 133 individuals and 6 dry skull specimens. Multiplanar reconstruction of the computed tomography images was performed, and the anatomical features of the NLD were studied in the coronal, sagittal, and axial planes. The long and short diameters of NLD were measured along its cross-section. The position of NLD was localized using the nostril, concha nasalis media, and medial orbital corner as landmarks. The free and open source software, 3D Slicer, was used for the segmentation of the NLD and 3D visualization of the superior and inferior openings of the NLD. RESULTS: The length, angle, and diameter of NLD were significantly influenced by the age in females compared to those in males. The inferior opening of the NLD could be located efficiently using the nostril and the midsagittal line while the superior opening of NLD could be located using the medial orbital corner. Third, 3D Slicer enabled us to measure the distance between the skin and the bony structure in the image. CONCLUSION: Our study indicates that the sex and age of the patient should be considered while selecting the optimal NLD stent for a patient, and that the precise location of NLD in reference to landmarks can simplify the surgical difficulties and reduce the risk of injury during the transnasal operation.
Assuntos
Pontos de Referência Anatômicos/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Ducto Nasolacrimal/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/diagnóstico por imagem , Adulto JovemRESUMO
We consider the inverse problem of optical tomography in the radiative transport regime. We report numerical tests of a direct reconstruction method that is suitable for use with large datasets. Reconstructions of experimental data obtained from a noncontact optical tomography system are also reported.
Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Óptica , Algoritmos , Modelos TeóricosRESUMO
Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction.
Assuntos
Adenoviridae/genética , Orelha Interna/citologia , Orelha Interna/fisiologia , Marcação de Genes/métodos , Vetores Genéticos/genética , Animais , Animais Recém-Nascidos , Cóclea/citologia , Cóclea/efeitos dos fármacos , Cóclea/fisiologia , Orelha Interna/efeitos dos fármacos , Vetores Genéticos/administração & dosagem , Proteínas de Fluorescência Verde/administração & dosagem , Proteínas de Fluorescência Verde/genética , CamundongosRESUMO
High-mobility group box chromosomal protein 1 (HMGB-1), a nuclear DNA binding protein, was recently rediscovered as a new proinflammatory cytokine. The purpose of this study was to determine HMGB-1 expression in vivo and to identify the effect of extracellular HMGB-1 in inflammatory process associated with bone destruction in cholesteatoma. We investigated the expression and location of HMGB-1 in the cholesteatoma and healthy skin using an immunofluorescence assay. We also detected apoptosis and DNA fragments in the cholesteatoma by TUNEL staining. HMGB-1 concentration in apoptotic supernatants from UV light-treated cells, culture supernatants and its translocation in cholesteatoma keratinocytes stimulated by supernatants from UV light-treated cells were measured by immunoblot analysis and immunofluorescence assay. Cultures of human cholesteatoma keratinocytes were exposed to CpG-DNA, HMGB-1, or CpG-DNA complexed to HMGB-1 for 24 h. Cytokines in the culture supernatant were measured by ELISA. In addition, levels of proinflammatory cytokines released by cholesteatoma keratinocytes stimulated by supernatants from UV light-treated cells with or without anti-HMGB-1 antibodies and supernatants from UV light-treated cells with DNase 1 were measured by enzyme-linked immunosorbent assay. The expression of HMGB-1 in cholesteatoma increased and it translocated both to the cytoplasm and extracellular space. Furthermore, the HMGB-1 concentration in supernatants increased significantly after addition of supernatants from UV light-treated cells. TNF-α and IL-1ß can be induced by purified HMGB-1 combined with CpG-DNA in the cholesteatoma keratinocytes. In addition, supernatants of apoptotic cells containing HMGB-1-DNA were effective in inducing TNF-α and IL-1ß secretion. This study suggested that persistent expression of extracellular HMGB-1 and DNA fragments in cholesteatoma leads to TNF-α and IL-1ß production, causing bone resorption and destruction. Thus, we have implicated that HMGB-1-DNA complexes might act as a key molecule involved in bone resorption associated with cholesteatoma.
Assuntos
Apoptose/genética , Colesteatoma/genética , Proteína HMGB1/biossíntese , Queratinócitos/patologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Colesteatoma/patologia , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Interleucina-1beta/biossíntese , Queratinócitos/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The aim of this study was to examine and assess comparative values of HRCT-based multiplanar reformation (MPR), volume rendering (VR) and virtual endoscope built on three-dimensional (3D) shaded-surface display (SSD-based CTVE) for detections of ossicular chain's damage in patients with otitis media. 70 human ears from 70 patients suffering by chronic otitis media or cholesteatoma, who were examined with a preoperative multi-slice computer tomography (MSCT) examination and tympanoplasty in our hospital were collected. The patients ossicular chains were reconstructed with the aforementioned three protocols and assessed via a three-point scoring system by three radiologists. Then, all the patients ossicular chains were reviewed by a surgeon and a radiologist via the same three-point scoring system used during surgeries at same time. By calculation, the Youden's index and coincidence rate were acquired without a significant difference for display of malleus. With regard to the incus, the Youden's index and coincidence rate of VR and MPR did not show any difference, however, both were higher than CTVE. For representation of the stapes, the accuracy of these three modalities is very low; especially, for the CTVE. In conclusion, both MPR and VR are relative robust, and CTVE is not effective for evaluation of small ossicular structures, particularly the stapes. Furthermore, the VR images are real 3D ones. Therefore, it could be the more valuable protocols for detection of the damage of ossicular chain in the patients with otitis media, and should be further applied in the future work.
Assuntos
Colesteatoma da Orelha Média/diagnóstico por imagem , Ossículos da Orelha/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada Multidetectores/métodos , Otite Média Supurativa/diagnóstico por imagem , Adolescente , Adulto , Criança , Colesteatoma da Orelha Média/cirurgia , Doença Crônica , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Otite Média Supurativa/cirurgia , Cuidados Pré-Operatórios , Timpanoplastia/métodos , Adulto JovemRESUMO
Reactivation of latent herpes simplex type 1 (HSV-1) and nerve inflammation have been shown to be involved in vertigo-related vestibular pathogenesis. Treatments of such diseases have been less than perfect. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress reactivation of HSV-1 in trigeminal ganglions. However, whether this drug can affect reactivation of HSV-1 in vestibular ganglions is unclear. Due to the difficulties of constructing in vivo animal models, in this study, we developed a vestibular ganglion culture system, in which vestibular neurons were latently or lytically infected with HSV-1. Indomethacin and celecoxib were selected to measure their effects on HSV-1. Trichostatin A was used to reactivate HSV-1 in latently infected neurons. Cycloxygenase-2, which is the target of NSAIDs, was induced by HSV-1 in the lytically infected cultures, with an increase of 14-fold. Although it appeared that indomethacin and celecoxib showed limited but concentration-dependent inhibition effects on viral production under our condition, indomethacin decreased reactivation rate of HSV-1 by about 20%. Though more in vitro or in vivo studies are needed to confirm the effects of the drugs, our study may provide a potential way to investigate the mechanism of HSV-related vestibular pathogenesis as well as new treatments of vertigo-related diseases.
Assuntos
Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Herpesvirus Humano 1/patogenicidade , Neurônios/enzimologia , Nervo Vestibular/virologia , Animais , Celecoxib , Células Cultivadas , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Indometacina/farmacologia , Neurônios/virologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Nervo Vestibular/citologia , Nervo Vestibular/metabolismoRESUMO
Hepatitis B Virus (HBV) infections pose a global public health challenge. Despite extensive research on this disease, the intricate mechanisms underlying persistent HBV infection require further in-depth elucidation. Recent studies have revealed the pivotal roles of immunometabolism and epigenetic reprogramming in chronic HBV infection. Immunometabolism have identified as the process, which link cell metabolic status with innate immunity functions in response to HBV infection, ultimately contributing to the immune system's inability to resolve Chronic Hepatitis B (CHB). Within hepatocytes, HBV replication leads to a stable viral covalently closed circular DNA (cccDNA) minichromosome located in the nucleus, and epigenetic modifications in cccDNA enable persistence of infection. Additionally, the accumulation or depletion of metabolites not only directly affects the function and homeostasis of immune cells but also serves as a substrate for regulating epigenetic modifications, subsequently influencing the expression of antiviral immune genes and facilitating the occurrence of sustained HBV infection. The interaction between immunometabolism and epigenetic modifications has led to a new research field, known as metabolic epigenomics, which may form a mutually reinforcing relationship with CHB. Herein, we review the recent studies on immunometabolism and epigenetic reprogramming in CHB infection and discuss the potential mechanisms of persistent HBV infection. A deeper understanding of these mechanisms will offer novel insights and targets for intervention strategies against chronic HBV infection, thereby providing new hope for the treatment of related diseases.
Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/genética , Replicação Viral/genética , Vírus da Hepatite B , Epigênese GenéticaRESUMO
CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47-SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano-degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.
Assuntos
Antígeno CD47 , Macrófagos , Receptores Imunológicos , Antígeno CD47/imunologia , Antígeno CD47/metabolismo , Animais , Receptores Imunológicos/metabolismo , Camundongos , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Animais de Doenças , Infarto do Miocárdio/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Antígenos de Diferenciação/imunologia , Fagocitose/efeitos dos fármacos , Biomimética/métodos , Humanos , EferocitoseRESUMO
Efferocytosis, mediated by the macrophage receptor MerTK (myeloid-epithelial-reproductive tyrosine kinase), is a significant contributor to cardiac repair after myocardial ischemia-reperfusion (MI/R) injury. However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK ï¼main effector receptor), and overexpression of "do not eat me" signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post-MI/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Herein, inspired by the application research of chimeric antigen receptor macrophages (CAR-Ms) in solid tumors, a genetically modified macrophage-based synergistic drug delivery strategy that effectively challenging the three major barriers in an integrated manner is developed. This strategy involves the overexpression of exogenous macrophages with CCR2 (C-C chemokine receptor type 2) and cleavage-resistant MerTK, as well as surface clicking with liposomal PEP-20 (a CD47 antagonist). In MI/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. This therapy focuses on inhibiting the initiation and promoting active resolution of inflammation, providing new insights for immune-regulatory therapy.
Assuntos
Antígeno CD47 , Macrófagos , Traumatismo por Reperfusão Miocárdica , c-Mer Tirosina Quinase , Animais , Antígeno CD47/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , c-Mer Tirosina Quinase/metabolismo , c-Mer Tirosina Quinase/genética , Camundongos Endogâmicos C57BL , Remodelação Ventricular/efeitos dos fármacos , Receptores CCR2/metabolismo , Engenharia Genética/métodos , Masculino , Lipossomos/química , Fagocitose/efeitos dos fármacos , EferocitoseRESUMO
Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.
Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Proteínas Hedgehog/farmacologia , Regeneração/efeitos dos fármacos , Proteína do Retinoblastoma/metabolismo , Animais , Proteína Quinase CDC2 , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclina B1/metabolismo , Ciclina D2/metabolismo , Ciclina D3/metabolismo , Regulação para Baixo , Células Ciliadas Auditivas/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
External auditory canal (EAC) carcinomas are frequently misdiagnosed. The aim of this study was to conduct a review of misdiagnosed cases and analyze the factors involved. This study was a retrospective assessment. Eighteen of 44 EAC carcinoma cases seen at the Eye and ENT Hospital were misdiagnosed. All medical records were retrospectively analyzed for the age, sex, presenting symptoms, type of misdiagnosis, computed tomographic (CT) or magnetic resonance imaging (MRI) findings, stage of the cancer, surgical approach, histopathological examination, adjunctive therapy (postoperative radiotherapy) and outcomes of treatment. Six cases were misdiagnosed as otitis media, five cases were misdiagnosed as otitis externa, and two cases were misdiagnosed as external auditory canal cholesteatomas. Other misdiagnoses were stenosis of the EAC, ear neuralgia, furuncle of the EAC, benign neoplasm of the EAC and pre-auricular fistula. Our analyses suggest that a biopsy should be conducted to obtain a histopathological diagnosis if an EAC carcinoma is suspected, in case otitis media or otitis externa does not respond to routine anti-bacterials. Head and neck MRI should be used to explore the involvement of soft tissues. Patients with bloody ear discharge and otalgia, particularly with temporal bone erosion seen in a CT scan, are highly likely to have a malignant carcinoma of the temporal bone.
Assuntos
Carcinoma/diagnóstico , Erros de Diagnóstico , Meato Acústico Externo , Neoplasias da Orelha/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Adolescente , Adulto , Idoso , Biópsia , Carcinoma/radioterapia , Carcinoma/cirurgia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Criança , Colesteatoma/diagnóstico , Terapia Combinada , Otopatias/diagnóstico , Neoplasias da Orelha/radioterapia , Neoplasias da Orelha/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/radioterapia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/cirurgia , Otite Externa/diagnóstico , Otite Média/diagnóstico , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/radioterapia , Rabdomiossarcoma/cirurgia , Sarcoma/diagnóstico , Sarcoma/radioterapia , Sarcoma/cirurgia , Osso Temporal , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A novel antibacterial indicator film was prepared by mixing corn starch with tangerine peel essential oil (TEO) Pickering emulsion emulsified by ultrasonic and esterified modified starch (UDSt), and then incorporated with purple corncob anthocyanin (PCA), which was used to monitor the freshness of pork. The results showed that the UDSt can effectively stabilize the TEO emulsion. PCA showed obvious color changes at different pH. With the increase of pH, the color of film changed from red to yellow, and its response to volatile ammonia changed from pink to cyan, showing better response ability. The loading of TEO conferred the film excellent bacteriostatic ability against E. coli and S. aureus. The film also had good ability of light blocking and free radical scavenging. In the process of pork deterioration, the antibacterial indicator film changed from pink to yellow, which was closely related to pork quality and had a good linear indicator correlation. The addition of TEO reduced the release of PCA in the antibacterial indicator film and helped to maintain the functional properties of the film. This type of antibacterial indicator film had considerable application potential in indicating food freshness.
RESUMO
The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.
RESUMO
The authors report here the clinical, genetic, molecular and biochemical characterisation of a large five-generation Han Chinese pedigree with maternally transmitted non-syndromic hearing loss. 17 of 35 matrilineal relatives exhibited variable severity and age at onset of sensorineural hearing loss. The average age at onset of hearing loss in matrilineal relatives of this family is 29 years, while matrilineal relatives among families carrying other mitochondrial DNA mutations developed hearing loss with congenital conditions or early age at onset. Molecular analysis of their mitochondrial genome identified the novel heteroplasmic T12201C mutation in the transfer RNA (tRNA)(His) gene. The levels of T12201C mutation in matrilineal relatives of this family correlated with the severity and age at onset of non-syndromic hearing loss. By contrast, other heteroplasmic mitochondrial DNA mutations often cause syndromic hearing loss. The T12201C mutation destabilises a highly conservative base-pairing (5A-68U) on the acceptor stem of tRNA(His). tRNA northern analysis revealed that the T12201C mutation caused an â¼75% reduction in the steady-state level of tRNA(His). An in vivo protein labeling analysis showed an â¼47% reduction in the rate of mitochondrial translation in cells carrying the T12201C mutation. Impaired mitochondrial translation is apparently a primary contributor to the marked reduction in the rate of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration or N,N,N,N-tetramethyl-p-phenylenediamine/ascorbate-promoted respiration. These data provide the first direct evidence that mitochondrial dysfunctions caused by the heteroplasmic tRNA(His) mutation lead to late-onset non-syndromic deafness. Thus, the authors' findings provide new insights into the understanding of pathophysiology and valuable information on the management and treatment of maternally inherited hearing loss.
Assuntos
DNA Mitocondrial/genética , Genes Mitocondriais , Perda Auditiva/genética , Mutação , RNA de Transferência de Histidina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Células Cultivadas , Criança , China , Família , Feminino , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Mães , Consumo de Oxigênio/genética , Linhagem , Análise de Sequência de DNARESUMO
Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC-MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein-protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. ß-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.