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Polymeric-based dielectric materials hold great potential as energy storage media in electrostatic capacitors. However, the inferior thermal resistance of polymers leads to severely degraded dielectric energy storage capabilities at elevated temperatures, limiting their applications in harsh environments. Here we present a flexible laminated polymer nanocomposite where the polymer component is confined at the nanoscale, achieving improved thermal-mechanical-electrical stability within the resulting nanocomposite. The nanolaminate, consisting of nanoconfined polyetherimide (PEI) polymer sandwiched between solid Al2O3 layers, exhibits a high energy density of 18.9 J/cm3 with a high energy efficiency of ~ 91% at elevated temperature of 200°C. Our work demonstrates that nanoconfinement of PEI polymer results in reduced diffusion coefficient and constrained thermal dynamics, leading to a remarkable increase of 37°C in glass-transition temperature compared to bulk PEI polymer. The combined effects of nanoconfinement and interfacial trapping within the nanolaminates synergistically contribute to improved electrical breakdown strength and enhanced energy storage performance across temperature range up to 250°C. By utilizing the flexible ultrathin nanolaminate on curved surfaces such as thin metal wires, we introduce an innovative concept that enables the creation of a highly efficient and compact metal-wired capacitor, achieving substantial capacitance despite the minimal device volume.
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The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of ß-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/ß-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.
Assuntos
Alopecia , Emulsões , Folículo Piloso , Panax notoginseng , Saponinas , Tensoativos , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Animais , Camundongos , Saponinas/administração & dosagem , Saponinas/farmacologia , Saponinas/química , Folículo Piloso/efeitos dos fármacos , Panax notoginseng/química , Tensoativos/química , Tensoativos/administração & dosagem , Feminino , Pele/efeitos dos fármacos , Pele/metabolismo , Movimento Celular/efeitos dos fármacos , Masculino , Absorção Cutânea/efeitos dos fármacos , Água/química , Administração CutâneaRESUMO
Flexible polymer-based dielectrics with high energy storage characteristics over a wide temperature range are crucial for advanced electrical and electronic systems. However, the intrinsic low dielectric constant and drastically degraded breakdown strength hinder the development of polymer-based dielectrics at elevated temperatures. Here, we propose a magnetic-assisted approach for fabricating a polyethyleneimine (PEI)-based nanocomposite with precisely aligned nanofibers within the polymer matrix, and with Al2O3 deposition layers applied on the surface. The resulting polymer nanocomposite exhibits simultaneously increased dielectric constant and enhanced breakdown strength at high temperatures compared to pristine PEI. The enhanced dielectric constant is contributed by the depolarization effect of out-of-plane orientated nanofibers in composite films, while the surficial Al2O3 layers, with a wide bandgap, effectively prevent charge injection and transport at the electrode/dielectric interface. The optimally aligned composite films exhibit a significantly enhanced discharged energy density of 6.5 J cm-3 at 150 °C, with approximately 41% and 132% enhancement compared to random films and pristine PEI films, respectively. Additionally, a metalized multilayer polymer-based capacitor utilizing this composite film produces a high capacitance of 88 nF, while demonstrating excellent cyclability and flexibility at 150 °C. This work offers an effective strategy for developing polymer-based composite dielectrics with superior capacitive performance at elevated temperatures and demonstrates the potential of fabricating high-quality flexible capacitors.
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Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG5k-block-PCL5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB's drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.
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Antibacterianos , Biofilmes , Ácidos Docosa-Hexaenoicos , Emulsões , Infecções por Pseudomonas , Pseudomonas aeruginosa , Tobramicina , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Tobramicina/química , Tobramicina/administração & dosagem , Emulsões/química , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Animais , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da PartículaRESUMO
Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn's disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease's initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.
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Doenças Inflamatórias Intestinais , Estresse Oxidativo , Humanos , Estresse Oxidativo/fisiologia , Doenças Inflamatórias Intestinais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores/metabolismo , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Espécies Reativas de Nitrogênio/metabolismo , AnimaisRESUMO
Effective capture and immobilization of volatile radioiodine from the off-gas of post-treatment plants is crucial for nuclear safety and public health, considering its long half-life, high toxicity, and environmental mobility. Herein, sulfur vacancy-rich Vs-Bi2S3@C nanocomposites were systematically synthesized via a one-step solvothermal vulcanization of CAU-17 precursor. Batch adsorption experiments demonstrated that the as-synthesized materials exhibited superior iodine adsorption capacity (1505.8 mg g-1 at 200 °C), fast equilibrium time (60 min), and high chemisorption ratio (91.7%), which might benefit from the nanowire structure and abundant sulfur vacancies of Bi2S3. Furthermore, Vs-Bi2S3@C composites exhibited excellent iodine capture performance in complex environments (high temperatures, high humidity and radiation exposure). Mechanistic investigations revealed that the I2 capture by fabricated materials primarily involved the chemical adsorption between Bi2S3 and I2 to form BiI3, and the interaction of I2 with electrons provided by sulfur vacancies to form polyiodide anions (I3-). The post-adsorbed iodine samples were successfully immobilized into commercial glass fractions in a stable form (BixOyI), exhibiting a normalized iodine leaching rate of 3.81 × 10-5 g m-2 d-1. Overall, our work offers a novel strategy for the design of adsorbent materials tailed for efficient capture and immobilization of volatile radioiodine.
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OBJECTIVE: Childhood trauma is considered as a critical risk factor for depression. Although many studies have investigated the pathway of Childhood trauma to depression, especially the mediating or moderating effects of cognitive emotion regulation strategies or neuroticism or stress perception, the results were inconsistent and the underlying psychological mechanisms of depression remain unclear. This study aims to explore the influence and mechanism of childhood trauma on depression in college students, and establish a full model among these interactive factors. METHODS: 1272 college students were surveyed using the childhood trauma questionnaire (CTQ), short version of center for epidemiologic studies depression scale (CES-D), Chinese perceived stress scale (CPSS), neuroticism extraversion openness five-factor inventory (NEO-FFI), and the Cognitive Emotion Regulation Questionnaire (CERQ). RESULTS: (1) Childhood trauma, neuroticism, stress perception, and maladaptive cognitive emotion regulation strategies were all significantly and positively correlated with depression among college students; (2) Stress perception and neuroticism act as a chain mediator between childhood trauma and depression in college students. (3) Maladaptive cognitive emotion regulation strategies play a moderating role in "childhood trauma-neuroticism-depression". CONCLUSION: Childhood trauma increases the risk of depression in college students by affecting neuroticism and stress perception, and high levels of maladaptive cognitive emotion regulation strategies link neuroticism and enhance the effect of childhood trauma on depression in college students.
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Experiências Adversas da Infância , Depressão , Testes Psicológicos , Autorrelato , Humanos , Depressão/psicologia , EstudantesRESUMO
Flexible pressure sensors are intensively demanded in various fields such as electronic skin, medical and health detection, wearable electronics, etc. MXene is considered an excellent sensing material due to its benign metal conductivity and adjustable interlayer distance. Exhibiting both high sensitivity and long-term stability is currently an urgent pursuit in MXene-based flexible pressure sensors. In this work, high-strength methylcellulose was introduced into the MXene film to increase the interlayer distance of 2D nanosheets and fundamentally overcome the self-stacking problem. Thus, concurrent improvement of the sensing capability and mechanical strength was obtained. By appropriately modulating the ratio of methylcellulose and MXene, the obtained pressure sensor presents a high sensitivity of 19.41 kPa-1 (0.88-24.09 kPa), good stability (10000 cycles), and complete biodegradation in H2O2 solution within 2 days. Besides, the sensor is capable of detecting a wide range of human activities (pulse, gesture, joint movement, etc.) and can precisely recognize spatial pressure distribution, which serves as a good candidate for next-generation wearable electronic devices.
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Peróxido de Hidrogênio , Metilcelulose , Nitritos , Elementos de Transição , Humanos , Movimento (Física) , Biodegradação AmbientalRESUMO
Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.
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Flavanonas , Glucosídeos , NF-kappa B , Psoríase , Camundongos , Animais , NF-kappa B/metabolismo , Fator de Transcrição AP-1/metabolismo , Imiquimode/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Células Th17 , Linhagem Celular , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Queratinócitos , Citocinas/metabolismo , Proliferação de Células , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
BACKGROUND: Hepatic steatosis is the leading cause of discarded liver grafts. Defatting steatotic liver grafts using drug combinations during ex vivo normothermic machine perfusion (NMP) has been reported. However, the effectiveness of NMP in reducing fat content using epigallocatechin gallate (EGCG) as a single defatting agent and its effect on lipid metabolism are poorly investigated. METHODS: In this study, an NMP system was set up to perfuse a steatotic liver from a rat model with 10 mM EGCG. Livers without EGCG served as NMP controls, whereas static cold-preserved livers in the University of Wisconsin medium were used as static cold storage controls. Liver enzyme, reactive oxygen species (ROS), histology, and lipid content assessments were conducted post-perfusion, complemented by lipidomics, RNA sequencing, and western blotting to determine the lipid metabolism changes. RESULTS: EGCG during NMP reduced hepatocellular injury markers and defatted steatotic liver grafts. Additionally, we observed a significant increase in triglyceride (TG) content in the perfusate post-NMP in the NMP + EGCG group, suggesting TG output from the liver. Furthermore, lipidomics analysis revealed that EGCG primarily affected metabolites involved in glycerophospholipid (GP) and glycerolipid (GL) metabolism. Further, the RNA sequencing indicated the modulation of these metabolic pathways via ECGC, which was associated with the downregulated Lpin1 and Gpat3 expression. CONCLUSIONS: EGCG defats steatotic livers as a single defatting agent during NMP by promoting GL and GP metabolism via decreasing Lpin1 and Agpat9 levels.
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Catequina/análogos & derivados , Fígado Gorduroso , Metabolismo dos Lipídeos , Humanos , Ratos , Animais , Lipidômica , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Perfusão , Triglicerídeos/metabolismo , Análise de Sequência de RNARESUMO
IMPORTANCE: Cytomegalovirus (CMV) has been used as a novel viral vector for vaccine development and gene therapy. Coronavirus disease 2019 is an infectious disease caused by the SARS-CoV-2 virus, which is highly mutable and is still circulating globally. The study showed that the CMV viral vector caused transient systemic infection and induced robust transgene expression in vivo. CMV vectors expressing different SARS-CoV-2 proteins were immunogenic and could elicit neutralizing antibodies against a highly mutated Omicron variant (BA.2). The expression level of receptor-binding domain (RBD) protein was higher than that of full-length S protein using CMV as a vaccine vector, and CMV vector expression RBD protein elicited higher RBD-binding and neutralizing antibodies. Moreover, the study showed that CMV-vectored vaccines would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. These works provide meaningful insights for the development of a CMV-based vector vaccine platform and the prevention and control strategies for SARS-CoV-2 infection.
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COVID-19 , Infecções por Citomegalovirus , Animais , Camundongos , Humanos , Vacinas contra COVID-19 , SARS-CoV-2/genética , COVID-19/prevenção & controle , Citomegalovirus/genética , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
BACKGROUND: Internet gaming disorder (IGD) is a formal mental disorder leading to personal and social impairment. Although it shares similar physical and psychosocial effects to substance use disorder, the psychological mechanisms underlying IGD remain unclear, although several researches have made significant contributions to its understanding. This study aims to elucidate the correlation between IGD, impulsive personality and risk preference of medical college students in China, from a questionnaire-based investigation. METHODS: Based on the cluster random sampling method, a questionnaire survey was conducted among medical college students in Northern Anhui, China from September 3 to October 27, 2020. The questionnaires included the Internet Gaming Disorder Scale (IGD-20), Chinese revised of Barratt Impulsiveness Scale Version 11 (BIS-11), and risk appetite index (RPI). Perform independent sample t-tests, analysis of variance (ANOVA), correlation analysis, and moderating effect analysis using SPSS 23.0. P < 0. 05 is considered statistically significant. RESULTS: 624 participants completed the survey, including 257 males (41.19%) and 367 females (58.81%). All participants were between 18 and 24 years. We found that in IGD and its six different dimensions and RPI, males scored significantly higher than females. Additionally, our finding revealed there is statistical significance in IGD and impulsiveness between gaming group with game time greater than or equal to 4 h and non-gaming group. The IGD and its six different dimensions, among which all except for mood modification are positively correlated with impulsiveness and RPI. Mediating effects indicate that RPI plays a partial mediating role between motor impulsiveness and IGD. CONCLUSION: The findings shows that there is a certain relationship between impulsivity and RPI, as well as IGD and its dimensions. RPI may be a mediator between impulsivity and IGD, and men have higher IGD. The findings supported the compensatory hypothesis. These findings may contribute to further research and development of intervention and prevention measures for IGD.
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Comportamento Aditivo , Estudantes de Medicina , Jogos de Vídeo , Masculino , Feminino , Humanos , Comportamento Aditivo/psicologia , Transtorno de Adição à Internet , Jogos de Vídeo/psicologia , Comportamento Impulsivo , InternetRESUMO
Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae.
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Microalgas , Nanopartículas , Edição de Genes , Sistemas CRISPR-Cas/genética , Microalgas/genética , Engenharia GenéticaRESUMO
BACKGROUND: Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression. METHODS: We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFß1 and AR signaling and mediating inherited PCa risk and progression. RESULTS: In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFß signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFß and AR signaling pathways, and activated the expression of TGFß1 via directly binding to a distal enhancer of TGFß1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6. CONCLUSIONS: Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFß1, thereby co-opting to TGFß1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Próstata/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Cromatina , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismoRESUMO
Wound regeneration with complete functions and skin appendages is still challenging in wound dressing application. Inspired by the efficient wound healing in the fetal environment, we developed a fetal milieu-mimicking hydrogel for accelerating wound healing simultaneously with hair follicle regeneration. To mimic the fetal extracellular matrix (ECM), which contains high content of glycosaminoglycans, hyaluronic acid (HA) and chondroitin sulfate (CS) were selected to fabricate hydrogels. Meanwhile, dopamine (DA) modification endowed hydrogels with satisfactory mechanical properties and multi-functions. The hydrogel encapsulated atorvastatin (ATV) and zinc citrate (ZnCit), namely HA-DA-CS/Zn-ATV, exhibited tissue adhesion, self-healing capacity, good biocompatibility, excellent anti-oxidant ability, high exudate absorption, and hemostasis property. In vitro results revealed that hydrogels exerted significant angiogenesis and hair follicle regeneration efficacy. In vivo results confirmed that hydrogels significantly promoted wound healing, and the closure ratio reached over 94 % after 14 days of hydrogels-treatment. The regenerated skin exhibited a complete epidermis, dense and ordered collagen. Furthermore, the number of neovessels and hair follicles in the HA-DA-CS/Zn-ATV group were 1.57- and 3.05-fold higher than those of the HA-DA-CS group. Thus, HA-DA-CS/Zn-ATV serves as multifunctional hydrogels for simulating the fetal milieu and achieving efficient skin reconstruction with hair follicle regrowth, exhibiting potential in clinical wound healing.
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Ácido Hialurônico , Hidrogéis , Hidrogéis/farmacologia , Ácido Hialurônico/farmacologia , Sulfatos de Condroitina/farmacologia , Dopamina/farmacologia , Cicatrização , Folículo Piloso , AntibacterianosRESUMO
Extracellular vesicles (EVs) have emerged as a promising platform for gene delivery owing to their natural properties and phenomenal functions, being able to circumvent the significant challenges associated with toxicity, problematic biocompatibility, and immunogenicity of the standard approaches. These features are of particularly interest for targeted delivery of the emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems. However, the current efficiency of EV-meditated transport of CRISPR/Cas components remains insufficient due to numerous exogenous and endogenous barriers. Here, we comprehensively reviewed the current status of EV-based CRISPR/Cas delivery systems. In particular, we explored various strategies and methodologies available to potentially improve the loading capacity, safety, stability, targeting, and tracking for EV-based CRISPR/Cas system delivery. Additionally, we hypothesise the future avenues for the development of EV-based delivery systems that could pave the way for novel clinically valuable gene delivery approaches, and may potentially bridge the gap between gene editing technologies and the laboratory/clinical application of gene therapies.
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Sistemas CRISPR-Cas , Vesículas Extracelulares , Estudos Prospectivos , Edição de Genes/métodos , Técnicas de Transferência de GenesRESUMO
Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.
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Psoríase , Fator de Necrose Tumoral alfa , Animais , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Fosforilação , Lipopolissacarídeos/farmacologia , Queratinócitos , Psoríase/patologia , Imiquimode/efeitos adversos , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Proliferação de Células , Modelos Animais de Doenças , PeleRESUMO
Chinese sacbrood virus (CSBV) is the most severe pathogen of Apis cerana, which leads to serious fatal diseases in bee colonies and eventual catastrophe for the Chinese beekeeping industry. Additionally, CSBV can potentially infect Apis mellifera by bridging the species barrier and significantly affect the productivity of the honey industry. Although several approaches, such as feeding royal jelly, traditional Chinese medicine, and double-stranded RNA treatments, have been employed to suppress CSBV infection, their practical applicabilities are constrained due to their poor effectiveness. In recent years, specific egg yolk antibodies (EYA) have been increasingly utilized in passive immunotherapy for infectious diseases without any side effects. According to both laboratory research and practical use, EYA have demonstrated superior protection for bees against CSBV infection. This review provided an in-depth analysis of the issues and drawbacks in this field in addition to provide a thorough summary of current advancements in CSBV studies. Some promising strategies for the synergistic study of EYA against CSBV, including the exploitation of novel antibody drugs, novel TCM monomer/formula determination, and development of nucleotide drugs, are also proposed in this review. Furthermore, the prospects for the future perspectives of EYA research and applications are presented. Collectively, EYA would terminate CSBV infection soon, as well as will provide scientific guidance and references to control and manage other viral infections in apiculture.
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Vírus de RNA , Viroses , Abelhas , Animais , Criação de Abelhas , Gema de Ovo , Vírus de RNA/genéticaRESUMO
Hepatic stellate cells (HSCs) upregulate hypoxia inducible factor 1 alpha (HIF-1α) expression in response to fibrosis-induced hypoxia. The mechanism by which HIF-1α promotes liver fibrosis in HSCs is not fully understood. In this study, we found that increased expression of α-SMA, HIF-1α and IL-6, as well as colocalization of α-SMA and HIF-1α, and HIF-1α and IL-6, were observed in liver fibrotic tissues of patients and a mouse model. HIF-1α expression induced IL-6 secretion in activated HSCs and the increase could be abolished by HIF-1α suppression or HIF1A gene knockdown. HIF-1α directly bound to the hypoxia response element (HRE) region in HSC IL6/Il6 promoters. Additionally, culturing naïve CD4 T cells with supernatant from HSCs in which HIF-1α is highly expressed increased IL-17A expression, and the expression could be abolished by HIF1A knockdown in LX2. In turn, the IL-17A-enriched supernatant induced IL-6 secretion in HSCs. Together, these results show that HIF-1α upregulates IL-6 expression in HSCs and induces IL-17A secretion through directly binding to the HRE of IL6 promoter.
Assuntos
Células Estreladas do Fígado , Interleucina-6 , Camundongos , Animais , Células Estreladas do Fígado/metabolismo , Interleucina-6/metabolismo , Interleucina-17/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
Increasing evidence suggests that long non-coding riboneucleic acids (lncRNAs), as competing endogenous RNA (ceRNA), play a key role in the initiation, invasion, and metastasis of cancer. As a new hypothesis, the lncRNA-micro RNA (miRNA)-messenger RNA (mRNA), ceRNA regulatory network has been successfully constructed in a variety of cancers. However, lncRNA, which plays a ceRNA function in endometrial cancer (EC), is still poorly understood. In this study, we downloaded EC expression profiling from The Cancer Genome Atlas database and used the R software "edgeR" package to analyze the differentially expressed genes between EC and normal endometrium samples. Then, differentially expressed (DE) lncRNAs, miRNAs and mRNAs were selected to construct a lncRNA-miRNA-mRNA prognosis-related regulatory network based on interaction information. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of lncRNAs in EC. Kaplan-Meier method and the log-rank test were used for survival analysis. Based on the "ceRNA hypothesis," we constructed a co-expression network of mRNA and lncRNA genes mediated by miRNA in the process of tumor genesis. Furthermore, we successfully constructed a dysregulated lncRNA-associated ceRNA network containing 96 DElncRNAs, 27 DEmiRNAs, and 74 DEmRNAs. Through Kaplan-Meier curve analysis, we found that 9 lncRNAs, 3 miRNAs, and 12 mRNAs were significantly correlated with the overall survival rate of patients among all lncRNAs, miRNAs, and mRNAs involved in ceRNA (Pâ <â .05). Our research provides a new perspective for the interaction among lncRNAs, miRNAs, and mRNA and lays the foundation for further research on the mechanism of lncRNAs in the occurrence of EC.