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Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here, we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. The VdPHB1 protein is localized to the intercellular space of cotton plants. Knock-out of the VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene-silenced cotton plants were more sensitive to V. dahliae with reduced expression of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein was concurrently repressed when VdPHB1 protein was expressed during infection. In summary, these results have revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.
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Ascomicetos , Gossypium , Doenças das Plantas , Gossypium/microbiologia , Gossypium/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Ascomicetos/patogenicidade , Ascomicetos/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Virulência , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Plantas Geneticamente Modificadas , VerticilliumRESUMO
Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.
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Microplásticos , Poluentes Químicos da Água , Microplásticos/toxicidade , Plásticos/toxicidade , Água do Mar , Solo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , AdsorçãoRESUMO
Polytetrafluoroethylene (PTFE) and expanded PTFE (ePTFE) are ideal for various applications. Because PTFE does not flow, even when heated above its melting point, PTFE components are fabricated using a process called paste extrusion. This process entails blending PTFE powder particles with a lubricant to form PTFE paste, which is subsequently preformed, extruded, expanded (in the case of ePTFE), and sintered. In this study, ethanol was proposed as an alternative green lubricant for PTFE processing. Not only is ethanol benign and biofriendly, it provides excellent wettability and processing benefits. Using ethanol as a lubricant, the shear viscosity of PTFE paste and its flow behavior during paste extrusion were investigated. Frequency sweeps using a parallel-plate rheometer were performed on PTFE paste samples and various grits of sandpaper were used to reduce wall slip of PTFE paste. A viscosity model was generated and a multiphysics software was used to simulate PTFE paste extrusion. The simulated extrusion pressure was compared to experimental data of actual paste extrusion. Flow visualization experiments using colored PTFE layers were conducted to reveal the flow profile of the PTFE paste. The morphology of the expanded ePTFE tubes was examined using scanning electron microscopy and the effect of expansion ratio on ePTFE morphology was quantified.
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Cardiovascular diseases plague human health because of the lack of transplantable small-diameter blood vessel (SDBV) grafts. Although expanded polytetrafluoroethylene (ePTFE) has the potential to be used as a biocompatible material for SDBV grafts, long-term patency is still the biggest challenge. As discussed in this paper, by virtue of a novel material formulation and a new and benign alcohol/water lubricating agent, biofunctionalized ePTFE blood vessel grafts aimed at providing long-term patency were fabricated. Compared to the most prevalent modification of PTFE, namely surface treatment, this method realized bulk treatment, which could guarantee homogeneous and long-lasting performance throughout PTFE products. These blood vessel grafts included embedded functional biomolecules, such as arginylglycylaspartic acid, heparin, and selenocystamine, using water as a solvent in paste extrusion and in the expansion of ePTFE. Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscope results confirmed the existence of these targeting biomolecules in the as-fabricated ePTFE blood vessel grafts. Meanwhile, the greatly improved biological functions of the grafts were demonstrated via live and dead assays, cell morphology, CD31 staining, nitric oxide (NO) release, and anticoagulation tests. This novel and benign material formulation and fabrication method provides an opportunity to produce multibiofunctional ePTFE blood vessel grafts in a single step, thus yielding a potent product with significant commercial and clinical potential.
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Prótese Vascular , Politetrafluoretileno , Materiais Biocompatíveis , Heparina , HumanosRESUMO
B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered. Despite a narrow range of affinity for BCMA, dramatic differences in CAR T cell expansion were observed between unique scFvs in a repeat antigen stimulation assay. These results were confirmed by screening in a MM xenograft model, where only the top preforming CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. The results of this screening identified a highly effective CAR T cell therapy with properties, including rapid in vivo expansion (>10,000-fold, day 6), eradication of large tumor burden, and durable protection to tumor re-challenge. We generated a bicistronic construct including a second-generation CAR and a truncated-epithelial growth factor receptor marker. CAR T cell vectors stemming from this work are under clinical investigation.
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Antígeno de Maturação de Linfócitos B/metabolismo , Imunoterapia Adotiva/métodos , Anticorpos de Cadeia Única/imunologia , Imunidade Adaptativa/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Herpesvirus Humano 4/imunologia , Humanos , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
During the regeneration of tissues and organs, growth factors (GFs) play a vital role by affecting cell behavior. However, because of the low half-life time and quick degradation of GFs, their stimulations on cells are relatively short and discontinuous. In this study, a releasing scaffold platform, consisting of polycaprolactone (PCL) nanofibers and vascular endothelial growth factor (VEGF)-encapsulated gelatin particles, was developed to extend the influence of GFs on mesenchymal stem cells (MSCs) and endothelial cells (ECs). The results showed that this kind of scaffold can direct the differentiation of MSCs to ECs and maintain the stability of the tubular structure, an indicator of the angiogenesis ability of ECs, for an extended period of time. Therefore, the results suggest the potential application of PCL/VEGF-encapsulated gelatin particles (PCL/VGPs) as a growth factor (GF)-releasing scaffold platform in vascular tissue engineering.
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Diferenciação Celular , Gelatina/química , Células-Tronco Mesenquimais/citologia , Poliésteres/química , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/farmacologia , Células Cultivadas , Liberação Controlada de Fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanofibras/química , Nanopartículas/química , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/químicaRESUMO
OBJECTIVE: Although the direct anterior approach can reduce muscle damage and ensure accurate prosthesis placement, the steep learning curve and increased risk of complications associated with DAA necessitate careful consideration. Therefore, we describe a technique for a novel percutaneously endoscopic-assisted total hip arthroplasty through mini bikini direct anterior approach (mDAA) and report the learning curve and initial outcomes. METHODS: The first 125 THA performed by a single surgeon between September 2020 and February 2022 using the anterior approach were included, comprising the initial 41 cases of bikini DAA (bDAA) and the subsequent 84 cases of mDAA. Outcome measures included perioperative outcomes and postoperative complications. The cumulative sum analysis (CUSUM) was used to determine the learning curve of anterior approach THA for each patient's ORT. Multivariable analysis was performed to determine risk correlation. RESULTS: A total of 125 anterior approach THA completed between 2020 and 2022 were identified. Among these, 41 were performed via bDAA and 84 via mDAA. No statistically significant differences were observed between the groups in terms of age, gender distribution, BMI or follow-up time. A significant reduction in ORT was noted, from 140 min for bDAA to 130 min for mDAA. Furthermore, there was a consistent decrease in LOI, LOS, and wound-healing problems. There was no statistically significant difference between groups with respect to Harris Hip Scores and other postoperative complications. The curve inflection points of the learning curve for the bDAA and mDAA group were located in the 22nd and 68th cases, respectively. The reduction of hemoglobin indicated a predicted increase in ORT. CONCLUSIONS: In this study, ORT, LOI, LOS, and wound-healing problems decreased overall in mDAA group. After mastering the bDAA technique, approximately 27 mDAA cases are needed to acquire proficiency in this technique. Hence, mDAA is a valuable alternative for those seeking smaller incisions, resolving wound healing problems, and aiming for enhanced recovery after surgery.
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Artroplastia de Quadril , Endoscopia , Curva de Aprendizado , Complicações Pós-Operatórias , Humanos , Artroplastia de Quadril/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Endoscopia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Estudos de Coortes , Duração da Cirurgia , Idoso de 80 Anos ou mais , AdultoRESUMO
Uniaxial cyclic stretching plays a pivotal role in the fields of tissue engineering and regenerative medicine, influencing cell behaviors and functionality based on physical properties, including matrix morphology and mechanical stimuli. This study delves into the response of endothelial cells to uniaxial cyclic strain within the geometric constraints of micro-nano fibers. Various structural scaffold forms of poly(l-lactide-co-caprolactone) (PLCL), such as flat membranes, randomly oriented fiber membranes, and aligned fiber membranes, were fabricated through solvent casting and electrospinning methods. Our investigation focuses on the morphological variation of endothelial cells under diverse geometric constraints and the mechanical-dependent release of nitric oxide (NO) on oriented fibrous membranes. Our results indicate that while uniaxial cyclic stretching promotes endothelial cell spreading, the anisotropy of the matrix morphology remains the primary driving factor for cell alignment. Additionally, uniaxial cyclic stretching significantly enhances NO release, with a notably stronger effect correlated to the increasing strain amplitude. Importantly, this study reveals that uniaxial cyclic stretching enhances the mRNA expression of key proteins, including talin, vinculin, rac, and nitric oxide synthase (eNOS).
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STUDY OBJECTIVES: Studies on the associations between sleep duration and metabolic syndrome in adolescents and children have reported mixed results. To shed more light on this issue, we conducted this meta-analysis by synthesizing the results of previous studies. METHODS: Studies were retrieved from PubMed, Ovid, Cochrane, and Embase from inception to October 2021. Fixed-effects models and random-effects models were used to analyze the effects of sleep time on metabolic syndrome in adolescents. RESULTS: Data from 7 studies, including 13,305 adolescents and children, were meta-analyzed. Compared with the control group, short sleep durations were not associated with a high prevalence of metabolic syndrome in adolescents and children using a random-effects model (odds ratio = 0.92, 95% confidence interval = 0.48-1.37, I2 = 56.5%, P = .378). Using a fixed-effects model on long sleep duration, this association was statistically significant (odds ratio = 0.57, 95% confidence interval = 0.38-0.76, I2 = 0.0%, P < .001) as a protective factor compared with shorter sleep duration. CONCLUSIONS: Long sleep duration, instead of short sleep duration, was significantly associated with a lower prevalence of metabolic syndrome among adolescents and children. CITATION: Xu Y, Hua J, Wang J, Shen Y. Sleep duration is associated with metabolic syndrome in adolescents and children: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(10):1835-1843.
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Síndrome Metabólica , Transtornos do Sono-Vigília , Humanos , Adolescente , Criança , Síndrome Metabólica/epidemiologia , Duração do Sono , Fatores de Risco , Sono , Transtornos do Sono-Vigília/epidemiologiaRESUMO
A convergent (outside-to-center) route was adopted to synthesize the precursors of quinoidal compounds in high yields of 85-93%. With subsequent rearrangement/dehydroxylation and oxidation, a series of thiophene-based quinoids with indandione or oxindole terminal groups were successfully synthesized. This strategy shows good compatibility with versatile central and terminal units, leading to quinoidal compounds with tunable properties.
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Experimental studies have shown that exercise and human adipose-derived stem cells (ADSCs) play positive roles in spinal cord injury (SCI). However, whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear. Thus, there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI. In this study, a thoracic 11 (T11) SCI contusion model was established in adult C57BL/6 mice. Exercise was initiated from 7 days post-injury and continued to 28 days post-injury, and approximately 1 × 105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI. Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale, von Frey filament test, Hargreaves method, and cold plate test. Histological studies (Eriochrome cyanine staining and immunohistochemistry) were performed at the end of the experiment (28 days post-injury). Exercise combined with administration of ADSCs partially improved early motor function (7, 14, and 21 days post-injury), mechanical allodynia, mechanical hypoalgesia, thermal hyperalgesia, and thermal hypoalgesia. Administration of ADSCs reduced white and gray matter loss at the lesion site. In addition, fewer microglia and astrocytes (as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, respectively) were present in the lumbar dorsal horn in the SCI + ADSCs and SCI + exercise + ADSCs groups compared with the sham group. Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCI-induced neuropathic pain.
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The mechanical properties of the anterior cruciate ligament (ACL) in the knee have been highlighted, but its role in the regulation of the joint microenvironment remains unclear, especially in the progression of Knee Osteoarthritis (KOA). Here, single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) data were integrated to reveal the transcriptional and epigenomic landscape of ACL in normal and OA states. We identified a novel subpopulation of fibroblasts in ACL, which provides new insights into the role of the ACL in knee homeostasis and disease. Degeneration of the ACL during OA mechanically alters the knee joint homeostasis and influences the microenvironment by regulating inflammatory- and osteogenic-related factors, thereby contributing to the progression of KOA. Additionally, the specific mechanism by which these Inflammation-associated Fibroblasts (IAFs) regulate KOA progression was uncovered, providing new foundation for the development of targeted treatments for KOA.
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Lesões do Ligamento Cruzado Anterior , Osteoartrite do Joelho , Humanos , Ligamento Cruzado Anterior , Articulação do Joelho , Fibroblastos , Análise de Célula ÚnicaRESUMO
PURPOSE: This study aims to develop and validate a concise tool for evaluating acupuncture expectancy that is easy to understand and conforms to acupuncture characteristics. MATERIALS AND METHODS: A draft was created using the Delphi consensus method. Reliability, validity, discrimination, and feasibility tests were conducted at the item and scale levels. RESULTS: The scale themes were defined as disease-related, treatment-related, process-related, and outcome-related. After two rounds of Delphi surveys with good experts' reliability (authority coefficients of experts were 0.86 and 0.87 in the two rounds) and agreement (Kendall's concordance coefficient of the participants were 0.33 and 0.15 in the two rounds, P < 0.05), 11 items (the mean score for item importance, full mark ratios, and coefficient of variation of items were ≥3.5, ≥25%, and ≤0.30, respectively) were included in the draft. A total of 145 individuals were recruited to test the draft. Reliability was assessed by Cronbach's α coefficient (0.90), split-half reliability coefficient (0.89), and test-retest reliability (Pearson's coefficient = 0.74, P < 0.05). Content validity was assessed by the content validity index (Item-CVI ≥ 0.78 and Scale-CVI/Ave = 0.92), and a confirmatory factor analysis was performed to assess the construct validity. The discrimination of scale items was evaluated by the critical ratio (CR > 3.00) and the homogeneity test (item-total correlations >0.40). Feasibility was assessed through the acceptance rate (recovery rate = 98.60%, response rate = 100%), completion rate (100%), and completion time (4.99 ± 6.80 min). CONCLUSION: The patients' expectancy scale of acupuncture (PESA) consists of 11 items with four themes, disease-related, treatment-related, process-related, and outcome-related. It has great reliability, validity, discrimination, and feasibility and has the potential to evaluate acupuncture expectancy in clinical trials.
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Terapia por Acupuntura , Humanos , Reprodutibilidade dos Testes , Psicometria/métodos , Inquéritos e Questionários , Análise FatorialRESUMO
A new genus and new species of freshwater crab, Jianghuaimon dabiense gen. et sp. nov., is described from Anhui and Hubei Provinces of China based on morphology and mitochondrial 16S rDNA sequences. Externally, the new genus resembles several other potamid genera from China. However, its combination of carapace, male pleon, third maxilliped, and uniquely structured male first gonopod distinguish it from the others. Phylogenetic analysis using the 16S gene supports the new genus new species and shows that it, together with morphologically similar Neilupotamon and Bottapotamon, form a distinct clade.
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Crustáceos , Decápodes , Animais , China , Água Doce , Masculino , FilogeniaRESUMO
Background: Perlodinella Klapálek, 1912 is a small stonefly genus in the Palearctic areas of China and its biodiversity is underestimated. New information: This paper reports a new species of Perlodinella, Perlodinellashennongjia sp. nov. in the Dajiuhu National Wetland Park of Shennongjia Forestry District, Hubei Province, central China. The description and illustrations of the new species are provided, based on male adults, female adults and eggs. The new species can be distinguished from its congeners by the characters of male and female genitalia and the egg structure.
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Environmental tobacco smoke (ETS) has become one of the most important sources of indoor air pollution. The study aimed to obtain the variation characteristics of typical air pollutant concentrations when people smoke in a closed room and explore the effect of the air-conditioner. A closed and air-conditioned room of 21 m2 was taken as the research object. Fine particulate matter (PM2.5) and total volatile organic compound (TVOC) were measured while 10 cigarettes were burnt in smoldering or smoking mode, with the air-conditioner on or off. The contents of nicotine in condensate samples were obtained by liquid chromatography. The impact of ETS on indoor air quality lasted for hours, causing typical pollutant concentrations to far exceed the Chinese standard. The PM2.5 produced by smoking was 11 times higher than by smoldering, but the TVOC produced by smoldering was more than by smoking. After one hour of the cigarette burning off, the PM2.5 concentration would be decreased by 96.1% with the air-conditioner on, in contrast to 67.9% with the air-conditioner off. Nicotine was detected in all samples of condensate from the air-conditioner. It is concluded that smoking cigarettes cannot be replaced by smoldering to evaluate the pollution of ETS. The air-conditioner has a positive effect on reducing the concentration of air pollutants produced by cigarette burning. More than 10% of the indoor nicotine may be taken away by condensate discharge, and its possible pollution should be paid attention to.Implications: This study provides new evidence of the effect of the split-type air-conditioner on ETS. The TVOC concentrations, which were less considered previously, were measured. PM2.5 concentration in human breathing zone can be reduced more quickly with the air-conditioner on. This study shows that there is a big difference in the concentrations of typical pollutants between smoking and smoldering. And it could be a guide for the formulation of relevant research methods. This study also demonstrates that the air conditioning condensate from the smoking room may contain nicotine. Attention should be paid to the recovery and utilization of such condensate.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Ambientais , Poluição por Fumaça de Tabaco , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , Humanos , Nicotina/análise , Material Particulado/análise , Fumar , Poluição por Fumaça de Tabaco/análise , Compostos Orgânicos Voláteis/análiseRESUMO
With the prevalence of cardiovascular diseases, developing cardiovascular supplements is becoming increasingly urgent. The ability of cells to rapidly adhere and proliferate to achieve endothelialization is extremely important for vascular grafts. In this work, we electrospun polytetrafluoroethylene (PTFE) nanofibrous membranes and used induced crystallization to manufacture poly(ε-caprolactone) (PCL) shish-kebab microstructures on PTFE nanofibers to overcome the inertness of PTFE, and promote cell adhesion and proliferation. PCL lamella periodically grew on the surface of PTFE nanofibers yielding a hierarchical structure, which improved the biocompatibility and mechanical properties of the PTFE nanofibrous membrane. The deposition of PCL lamella improved the hydrophilicity of electrospun PTFE nanofibers membrane, leading to good cell proliferation and adhesion. Also, due to the surface inertness of the substrate material PTFE, this PTFE/PCL composite film has good anti-platelet adhesion properties. Furthermore, cell proliferation could be regulated by controlling the integrity of the PCL crystal network. The vascular patch showed similar mechanical properties to natural blood vessels, providing a new strategy for vascular tissue engineering.
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Nanofibras , Nanofibras/química , Alicerces Teciduais/química , Politetrafluoretileno , Poliésteres/farmacologia , Poliésteres/química , Engenharia Tecidual , Proliferação de CélulasRESUMO
Mitochondrial dysfunction is related to the pathogenesis of osteoarthritis (OA); however, there are no effective drugs to treat OA for maintaining mitochondrial homeostasis. Studies have shown that mitochonic acid-5 (MA-5) has a protective effect against mitochondrial damage and plays a role in mitophagy. However, it is not clear whether MA-5 has a beneficial effect on inflammatory articular cartilage. Here, human OA cartilage was obtained from patients undergoing total joint replacement. Interleukin-1ß (IL-1ß) was used to stimulate chondrocytes and induce inflammatory injury. Cell Counting Kit-8, TUNEL, and flow cytometry assays were used to assess apoptosis. Gene expression was examined using quantitative reverse transcription-polymerase chain reaction. Mitochondrial function was evaluated using immunoblotting, mitochondrial membrane potential assay, JC-1 staining, and immunofluorescence analysis. Mitophagy was detected using immunoblotting and immunofluorescence. 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), a specific inhibitor of Sirtuin 3 (SIRT3), was used to block the SIRT3/Parkin pathway. Mitophagy in the cartilage sections was evaluated via immunohistochemistry. IL-1ß was found to induce chondrocyte apoptosis by inhibiting SIRT3 expression and mitophagy. In addition, inflammatory damage reduced the mitochondrial membrane potential and promoted the production of intracellular reactive oxygen species (ROS), leading to increased mitochondrial division, mitochondrial fusion inhibition, and the consequent mitochondrial damage. In contrast, the MA-5 treatment inhibited excessive ROS production by upregulating mitophagy, maintaining the mitochondrial membrane potential, and reducing mitochondrial apoptosis. After chemically blocking SIRT3 with 3-TYP, Parkin-related mitophagy was also inhibited, an effect that was prevented by pretreatment of the chondrocytes with MA-5, thereby suggesting that SIRT3 is upstream of Parkin. Overall, MA-5 was found to enhance the activity of SIRT3, promote Parkin-dependent mitophagy, eliminate depolarized/damaged mitochondria in chondrocytes, and protect cartilage cells. In conclusion, MA-5 inhibits IL-1ß-induced oxidative stress and protects chondrocytes by upregulating the SIRT3/Parkin-related autophagy signaling pathway.
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Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.
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Hidrogéis , Lipossomos , Encéfalo , Glutationa , Polissacarídeos Bacterianos , TemperaturaRESUMO
tRNA-derived fragments (tRFs) have been reported to have critical regulatory roles in osteoarthritis (OA). Recent studies have suggested that autophagy promotes the homeostasis of the extracellular matrix of chondrocytes in OA. However, the role of tRFs in posttranscriptional gene regulation during autophagy in OA is unknown. Therefore, we explored the role of tRF-5009A in the posttranscriptional gene regulation of autophagy and cartilage degeneration in OA. Using RNA sequencing, we identified tRF-5009A, the tRNAValCAC-derived fragment, in OA tissues and explored its expression by quantitative reverse transcription PCR and fluorescence in situ hybridization. We further investigated the relationship between the expression of tRF-5009A and clinical factors in OA. Chondrocytes were transfected with a tRF-5009A inhibitor or mimic to determine their functions, including in relation to autophagy and the cartilage phenotype. A rescue experiment and dual-luciferase reporter assay were conducted to determine whether the 3'-untranslated region (UTR) of mTOR contains a tRF-5009A-binding site. tRF-5009A was downregulated in the cartilage of OA knees, especially in damaged areas. mTOR was highly expressed in damaged cartilage and negatively correlated with the expression of tRF-5009A; transfection with a tRF-5009A inhibitor promoted the expression of mTOR and suppressed autophagy, whereas transfection with a tRF-5009A mimic had the opposite effect. A dual-luciferase reporter assay showed that tRF-5009A silenced the expression of mTOR by binding to its 3'-UTR. Thus, tRF-5009A regulates autophagy and cartilage degeneration in OA by targeting mTOR. In summary, these findings provide an additional tool for the clinical diagnosis and novel targeted therapy of OA.