RESUMO
The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients' AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.
Assuntos
Inibidores da Angiogênese , Humor Aquoso , Retinopatia Diabética , Glaucoma Neovascular , Injeções Intravítreas , Lipidômica , Lipídeos , Fator A de Crescimento do Endotélio Vascular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Humor Aquoso/metabolismo , Masculino , Glaucoma Neovascular/metabolismo , Glaucoma Neovascular/tratamento farmacológico , Glaucoma Neovascular/etiologia , Feminino , Inibidores da Angiogênese/uso terapêutico , Lipidômica/métodos , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Lipídeos/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Pressão Intraocular , Metabolismo dos LipídeosRESUMO
Separating helium (He) and hydrogen (H2), two gases that are extremely similar in molecular size and condensation properties, presents a formidable challenge in the helium industry. The development of membranes capable of precisely differentiating between these gases is crucial for achieving large-scale, energy-efficient He/H2 separation. However, the limited selectivity of current membranes has hindered their practical application. In this study, we propose a novel approach to overcome this challenge by engineering submicroporous membranes through the fluorination of partially carbonized hollow fibers. We demonstrate that the fluorine substitution on the inner rim of the micropore walls within the carbon hollow fibers enables tunability of the microporous architecture. Furthermore, it enhances interactions between H2 molecules and the micropore walls through the polarization and hydrogen bonding induced by C-F bonds, resulting in simultaneous improvements in both He/H2 diffusivity and solubility selectivities. The fluorinated HFM-550-F-1â min membrane exhibits exceptional mixed-gas separation performance, with a binary mixed-gas He/H2 selectivity of 10.5 and a ternary mixed-gas He/(H2+CO2) selectivity of 20.8, at 40â bar feed pressure and 35 °C, surpassing all previously reported polymer-based gas separation membranes, and remarkable plasticization resistance and long-term continuous stability over 30â days.
RESUMO
Molybdenum disulfide (MoS2) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS2during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS2nanosheets were fabricated on carbon cloth (CC) using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS2exhibits excellent HER activity due to the combination of optimized microstructures and coupling with CC. Our findings provide new insights to design advanced MoS2-based electrocatalysts for HER.
RESUMO
Biosensors show promising prospects in the assays of various targets due to their advantages of high sensitivity, good selectivity and rapid response. Molecular recognition is a key event of biosensors, which usually involves the interaction of antigen-antibody, aptamer-target, lectin-sugar, boronic acid-diol, metal chelation and DNA hybridization. Metal ions or complexes can specifically recognize phosphate groups in peptides or proteins, obviating the use of biorecognition elements. In this review, we summarized the design and applications of biosensors with metal ion-phosphate chelation interaction for molecular recognition. The sensing techniques include electrochemistry, fluorescence, colorimetry and so on.
Assuntos
Técnicas Biossensoriais , Fosfatos , Técnicas Biossensoriais/métodos , Oligonucleotídeos , Hibridização de Ácido Nucleico , Metais/química , ÍonsRESUMO
Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.
Assuntos
Nanopartículas de Magnetita , Ácido Nitrilotriacético , Fluorescência , Níquel , Histidina , Peptídeos , Peptídeo HidrolasesRESUMO
BACKGROUND: Clematis species are attractive ornamental plants with a variety of flower colors and patterns. Heat stress is one of the main factors restricting the growth, development, and ornamental value of Clematis. Clematis lanuginosa and Clematis crassifolia are large-flowered and evergreen Clematis species, respectively, that show different tolerance to heat stress. We compared and analyzed the transcriptome of C. lanuginose and C. crassifolia under heat stress to determine the regulatory mechanism(s) of resistance. RESULTS: A total of 1720 and 6178 differentially expressed genes were identified from C. lanuginose and C. crassifolia, respectively. The photosynthesis and oxidation-reduction processes of C. crassifolia were more sensitive than C. lanuginose under heat stress. Glycine/serine/threonine metabolism, glyoxylic metabolism, and thiamine metabolism were important pathways in response to heat stress in C. lanuginose, and flavonoid biosynthesis, phenylalanine metabolism, and arginine/proline metabolism were the key pathways in C. crassifolia. Six sHSPs (c176964_g1, c200771_g1, c204924_g1, c199407_g2, c201522_g2, c192936_g1), POD1 (c200317_g1), POD3 (c210145_g2), DREB2 (c182557_g1), and HSFA2 (c206233_g2) may be key genes in the response to heat stress in C. lanuginose and C. crassifolia. CONCLUSIONS: We compared important metabolic pathways and differentially expressed genes in response to heat stress between C. lanuginose and C. crassifolia. The results increase our understanding of the response mechanism and candidate genes of Clematis under heat stress. These data may contribute to the development of new Clematis varieties with greater heat tolerance.
Assuntos
Clematis , Transcriptoma , Clematis/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/genéticaRESUMO
The biological nervous system possesses a powerful information processing capability, and only needs a partial signal stimulation to perceive the entire signal. Likewise, the hardware implementation of an information processing system with similar capabilities is of great significance, for reducing the dimensions of data from sensors and improving the processing efficiency. Here, it is reported that indium-gallium-zinc-oxide thin film phototransistors exhibit the optoelectronic switching and light-tunable synaptic characteristics for in-sensor compression and computing. Phototransistor arrays can compress the signal while sensing, to realize in-sensor compression. Additionally, a reservoir computing network can also be implemented via phototransistors for in-sensor computing. By integrating these two systems, a neuromorphic system for high-efficiency in-sensor compression and computing is demonstrated. The results reveal that even for cases where the signal is compressed by 50%, the recognition accuracy of reconstructed signal still reaches ≈96%. The work paves the way for efficient information processing of human-computer interactions and the Internet of Things.
Assuntos
Processamento Eletrônico de Dados , HumanosRESUMO
ßII spectrin (ß2SP) is encoded by Sptbn1 and is involved in the regulation of various cell functions. ß2SP contributes to the formation of the myelin sheath, which may be related to the mechanism of neuropathy caused by demyelination. As one of the main features of cerebral ischemia, demyelination plays a key role in the mechanism of cerebral ischemia injury. Here, we showed that ß2SP levels were increased, and this molecule interacted with TET2 after ischemic injury. Furthermore, we found that the level of TET2 was decreased in the nucleus when ß2SP was knocked out after oxygen and glucose deprivation (OGD), and the level of 5hmC was reduced in the OGD+ß2SP KO group. In contrast, the expression of ß2SP did not change in TET2 KO mice. In addition, the 5hmC sequencing results revealed that ß2SP can affect the level of 5hmC, the differentially hydroxymethylated region (DhMR) mainly related with the Calcium signalling pathway, cGMP-PKG signalling pathway, Wnt signalling pathway and Hippo signalling pathway. In summary, our results suggest that ß2SP could regulate the gene 5hmC by interacted with TET2 and will become a potential therapeutic target for ischemic stroke.
Assuntos
5-Metilcitosina/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , Proteínas dos Microfilamentos/metabolismo , Animais , Biomarcadores , Isquemia Encefálica/patologia , Proteínas de Transporte/genética , Células Cultivadas , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Modelos Animais de Doenças , Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Complexos Multiproteicos , Ligação Proteica , Transporte ProteicoRESUMO
Electrocatalysis of oxygen evolution reaction (OER), one of the most important members in clean and efficient energy conversion, requires increasing studies on reaction process analysis, catalyst investigation and evaluation and so on throughin situexperiments. The bottleneck is the difficulties on clear and precise understanding towards the multi-step reactions with fast reaction rates. Interdigitated array (IDA) electrodes with sensitive responses on the generation, transfer and collection of reaction products are proposed and utilized as a convenient and effective tool toin situmonitor and characterize the reaction thermodynamics and kinetics information. Herein, nickel-iron hydroxide, a promising and novel OER catalyst, is chosen as the candidate to demonstrate the merit of IDA on studying the OER. With the generator-collector mode, the real-time oxygen evolution process is monitored precisely with the IDA collector, distinguished it from the general catalytic current which is normally recorded with conventional electrochemical method. In another word, the actual faradaic efficiency was observed experimentally with IDA electrodes, which is often misled as 100% in many works. The diffusion of the reaction products has been 'seen' as well with the generator-collector mode. This general tool (IDA) may make more contributions on the study of reaction process of all electrocatalytical reactions.
RESUMO
Tailoring the microporosity of intrinsically microporous polymers at the atomic level is one of the biggest challenges in achieving high-performance polymeric gas separation membranes. In this study, for the first time, the Al2 O3 atomic layer deposition (ALD) technique was used to modify the microporosity of a typical polymer of intrinsic microporosity (PIM-1) at the atomic level. PIM-1 with six ALD cycles (PIM-1-Al2 O3 -6) exhibited simultaneous high thermal, mechanical, pure- and mixed-gas separation, and anti-aging properties. The O2 /N2 , H2 /N2 , and H2 /CH4 separation performances were adequate above the latest trade-off lines. PIM-1-Al2 O3 -6 showed CO2 and O2 permeabilities of 624 and 188â Barrer, combined with CO2 /CH4 and O2 /N2 selectivities of 56.2 and 8.8, respectively. This significantly enhanced performance was attributed to the strong size sieving effect induced by the Al2 O3 deposition.
RESUMO
The mainstream approach to antiviral drugs against COVID-19 is to focus on key stages of the SARS-CoV-2 life cycle. The vast majority of candidates under investigation are repurposed from agents of other indications. Understanding protein-inhibitor interactions at the molecular scale will provide crucial insights for drug discovery to stop this pandemic. In this article, we summarize and analyze the most recent structural data on several viral targets in the presence of promising inhibitors for COVID-19 in the context of the perspective of modes of action (MOA) to unravel insightful mechanistic features with atomistic resolution. The targets include spike glycoprotein and various host proteases mediating the entry of the virus into the cells, viral chymotrypsin- and papain-like proteases, and RNA-dependent RNA polymerase. The main purpose of this review is to present detailed MOA analysis to inspire fresh ideas for both de novo drug design and optimization of known scaffolds to combat COVID-19.
Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Descoberta de Drogas , SARS-CoV-2/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Antivirais/química , COVID-19/metabolismo , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , SARS-CoV-2/fisiologia , Bibliotecas de Moléculas Pequenas/química , Internalização do Vírus/efeitos dos fármacosRESUMO
Interlayered thin-film nanocomposite membranes (TFNi) are an emerging type of membranes with great potential to overcome the permeability-selectivity upper bound of conventional thin-film composite (TFC) nanofiltration and reverse osmosis membranes. However, the exact roles of the interlayer and the corresponding mechanisms leading to enhanced separation performance of TFNi membranes remain poorly understood. This study reports a polydopamine (PDA)-intercalated TFNi nanofiltration membrane (PA-PSF2, PDA coating time of 2 h) that possessed nearly an order of magnitude higher water permeance (14.8 ± 0.4 Lm-2 h-1 bar-1) than the control TFC membrane (PA-PFS0, 2.4 ± 0.5 Lm-2 h-1 bar-1). The TFNi membrane further showed enhanced rejection toward a wide range of inorganic salts and small organic molecules (including antibiotics and endocrine disruptors). Detailed mechanistic investigation reveals that the membrane separation performance was enhanced due to both the direct "gutter" effect of the PDA interlayer and its indirect effects resulting from enhanced polyamide formation on the PDA-coated substrate, with the "gutter" effect playing a more dominant role. This study provides a mechanistic and comprehensive framework for the future development of TFNi membranes.
Assuntos
Membranas Artificiais , Nylons , Filtração , Indóis , PolímerosRESUMO
Fe3O4/Polyvinylidene fluoride (PVDF) three-channel hollow fiber catalytic membrane was successfully fabricated via non-solvent induced phase inversion and used for organic wastewater degradation in this work. The effects of Fe3O4 nanoparticles addition on the surface and cross-section morphologies, hydrophilicity and thermal properties of the catalytic membrane were characterized by the field emission scanning electron microscopy (SEM), water contact angle and thermogravimetric analysis (TGA), respectively. The obtained catalytic membrane exhibited good hydrophilicity, a high pure water flux of 175.8 L m-2 h-1 and a high removal of methylene blue (up to 97.6%) with Fenton catalytic reaction. Meanwhile, the catalytic membrane shows excellent anti-fouling property due to the presence of Fenton reaction. Our results show that Fe3O4/PVDF three-channel hollow fiber catalytic membrane was a promising alternative for the degradation of organic contaminants.
Assuntos
Membranas Artificiais , Águas Residuárias , Permeabilidade , PolivinilRESUMO
OBJECTIVE: This study was conducted to explore the association of microRNA (miR)-125a and miR-125b with acute respiratory distress syndrome (ARDS) risk and to investigate their correlation with clinical characteristics and prognosis in sepsis patients. METHODS: Totally 150 sepsis patients admitted to our hospital were consecutively enrolled and another 150 healthy subjects were enrolled as healthy controls (HCs). Their blood samples were collected for miR-125a and miR-125b detection by real-time quantitative polymerase chain reaction. Besides, ARDS occurrence and 28-day mortality were documented in all sepsis patients. RESULTS: MiR-125a and miR-125b relative expressions were increased in ARDS-sepsis patients/non-ARDS-sepsis patients compared with HCs, while only miR-125b but not miR-125a was elevated in ARDS-sepsis patients compared with non-ARDS-sepsis patients. Receiver operating characteristic (ROC) curve presented that miR-125a (AUC: 0.650, 95%CI: 0.549-0.750) and miR-125b (AUC: 0.739, 95%CI: 0.653-0.823) could differentiate ARDS-sepsis patients from non-ARDS-sepsis patients, and miR-125b was of increased predictive value compared with miR-125a numerically. In sepsis patients, miR-125a relative expression was positively associated with serum creatinine (Scr), chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and miR-125b was positively associated with Scr, C-reactive protein (CRP), APACHE II score, SOFA score, and chronic obstructive pulmonary disease. All sepsis patients were categorized into survivors and deaths according to 28-day mortality, and miR-125b but not miR-125a was upregulated in deaths compared with survivors. CONCLUSION: Both of miR-125a and miR-125b predict ARDS risk, while only miR-125b is of value in prognosis prediction in sepsis patients.
Assuntos
MicroRNAs/genética , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/genética , Sepse/complicações , Sepse/genética , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Modelos Logísticos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Fatores de Risco , Análise de SobrevidaRESUMO
OBJECTIVE: This study aimed to explore the predictive value of microRNA (miR)-125a and miR-125b for sepsis risk, and their correlations with inflammation, disease severity, and 28-day mortality in sepsis patients. METHODS: Totally, 150 sepsis patients and 150 healthy controls (HCs) were enrolled. Plasma samples were separated from blood samples obtained from sepsis patients and HCs to detect miR-125a and miR-125b expressions by real-time quantitative polymerase chain reaction. Besides, the 28-day mortality of sepsis patients was assessed. MiR-125a and miR-125b expressions were elevated in sepsis patients compared with HCs, and further receiver operating characteristics (ROC) curve analysis displayed that miR-125a (area under the curve (AUC): 0.749, 95% CI: 0.695-0.803) and miR-125b (AUC: 0.839, 95% CI: 0.795-0.882) could predict sepsis risk. As for inflammation, no correlation of miR-125a with C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-17, and IL-23 was observed in sepsis patients, while miR-125b was positively associated with CRP, TNF-α, IL-6, IL-17, and IL-23. Regarding disease severity, miR-125a and miR-125b were positively correlated with acute physiology and chronic health care evaluation II and sequential organ failure assessment score in sepsis patients. Besides, ROC curve analysis exhibited that miR-125a failed to predict 28-day mortality risk (AUC: 0.588, 95% CI: 0.491-0.685) in sepsis patients, while miR-125b had a potential value in predicting elevated 28-day mortality risk (AUC: 0.699, 95% CI: 0.603-0.795). CONCLUSION: Both miR-125a and miR-125b predict sepsis risk, while only miR-125b exhibits the potency for disease management and prognosis prediction in sepsis patients.
Assuntos
Inflamação/genética , MicroRNAs/sangue , Sepse/genética , APACHE , Idoso , Biomarcadores/sangue , Citocinas/sangue , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos , Humanos , Inflamação/sangue , Inflamação/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Escores de Disfunção Orgânica , Prognóstico , Sepse/sangue , Sepse/mortalidade , Sepse/terapiaRESUMO
Clematis florida is a popular ornamental vine species known for diverse colors and shapes of its flowers but not for scent. Here we investigated the composition and biosynthesis of floral scent in 'Kaiser', a fragrant cultivar of C. florida that has sterile flowers. Volatile profiling revealed that flowers of 'Kaiser' emit more than 20 compounds, with monoterpenes being most abundant. Among the three floral organs, namely sepals, transformed-petals, and ovaries, ovaries had the highest rates of total volatile emission. To determine the molecular mechanism underlying floral scent biosynthesis in 'Kaiser', we sequenced a flower transcriptome and searched the transcriptome for terpene synthase genes (TPSs), which are key genes for terpene biosynthesis. Among the TPS genes identified, three were putative intact full-length genes and were designated CfTPS1, CfTPS2, and CfTPS3. Phylogenetic analysis placed CfTPS1, CfTPS2, and CfTPS3 to the TPS-g, TPS-b, and TPS-a subfamily, respectively. Through in vitro enzyme assays with Escherichia coli-expressed recombinant proteins, both CfTPS1 and CfTPS2 were demonstrated to catalyze the conversion of geranyl diphosphate to linalool, the most abundant constituent of C. florida floral scent. In addition, CfTPS1 and CfTPS2 produced the sesquiterpene nerolidol from (E,E)-farnesyl diphosphate. CfTPS3 showed sesquiterpene synthase activity and produced multiple products in vitro. All three CfTPS genes showed higher levels of expression in sepals than those in transformed-petals and ovaries. Our results show that despite being sterile, the flowers of 'Kaiser' have normal mechanisms for floral scent biosynthesis that make the flowers fragrant.
Assuntos
Vias Biossintéticas , Clematis/química , Flores/química , Odorantes/análise , Infertilidade das Plantas , Sequência de Aminoácidos , Biocatálise , Clematis/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Anotação de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/química , Terpenos/metabolismo , Transcriptoma/genética , Compostos Orgânicos Voláteis/análiseRESUMO
OBJECTIVES: Our study aimed to probe the effects of rosiglitazone treatment on a severe acute pancreatitis (SAP) model induced by caerulein and investigate the underlying mechanism. METHODS: Differentially expressed messenger RNAs (mRNAs) in the mice of a SAP group were screened out by microarray analysis. The inflammatory response pathway was obtained from the online website DAVID Bioinformatics Resources 6.8. The interactions of caerulein and its target proteins were shown by search tool for interactions of chemicals (STITCH). Functional interactions of the genes associated with pancreatitis and the target proteins of caerulein were obtained with search tool for interactions of chemicals (STRING). SAP mice were established by hourly intraperitoneal injection of caerulein. Rosiglitazone was used as treatment drug, and pancreatic inflammation was assessed. The expression of Socs3 was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of interleukin (IL)-6, IL-1b, and Egr1 were studied by RT-PCR and Western blot analysis. RESULTS: The GSE77983 data were analyzed, and the results showed that Socs3 was overexpressed in SAP tissues. The inflammation response pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of rosiglitazone in mice, the serum levels of amylase and lipase were decreased. Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in pancreatic tissues were downregulated. CONCLUSIONS: Rosiglitazone could protect mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory response pathway.
Assuntos
Pancreatite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Rosiglitazona/uso terapêutico , Animais , Ceruletídeo/administração & dosagem , Ceruletídeo/farmacologia , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Injeções Intraperitoneais , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Pancreatite/induzido quimicamente , Substâncias Protetoras/farmacologia , RNA Mensageiro/metabolismo , Rosiglitazona/farmacologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismoRESUMO
Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived invasive and metastatic tumor of the skin. It is the second-most commonly diagnosed form of skin cancer striking 200 000 Americans annually. Further, in organ transplant patients, there is a 65- to 100-fold increased incidence of cSCC compared to the general population. Excision of cSCC of the head and neck results in significant facial disfigurement. Therefore, increased understanding of the mechanisms involved in the pathogeneses of cSCC could identify means to prevent, inhibit, and reverse this process. In our previous studies, inhibition of fibroblast growth factor receptor (FGFR) significantly decreased ultraviolet B-induced epidermal hyperplasia and hyperproliferation in SKH-1 mice, suggesting an important role for FGFR signaling in skin cancer development. However, the role of FGFR signaling in the progression of cSCC is not yet elucidated. Analysis of the expression of FGFR in cSCC cells and normal epidermal keratinocytes revealed protein overexpression and increased FGFR2 activation in cSCC cells compared to normal keratinocytes. Further, tumor cell-specific overexpression of FGFR2 was detected in human cSCCs, whereas the expression of FGFR2 was low in premalignant lesions and normal skin. Pretreatment with the pan-FGFR inhibitor; AZD4547 significantly decreased cSCC cell-cycle traverse, proliferation, migration, and motility. Interestingly, AZD4547 also significantly downregulated mammalian target of rapamycin complex 1 and AKT activation in cSCC cells, suggesting an important role of these signaling pathways in FGFR-mediated effects. To further bolster the in vitro studies, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice with SCC12A tumor xenografts treated with AZD4547 (15 mg/kg/bw, twice weekly oral gavage) exhibited significantly decreased tumor volume compared to the vehicle-only treatment group. The current studies provide mechanistic evidence for the role of FGFR and selectively FGFR2 in the early progression of cSCC and identifies FGFR as a putative therapeutic target in the treatment of skin cancer.
Assuntos
Benzamidas/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Piperazinas/farmacologia , Pirazóis/farmacologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Cutâneas/tratamento farmacológico , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Epiderme/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Humanos , Queratinócitos/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Polyamide-based thin film composite (TFC) membranes are generally optimized for salt rejection but not for the removal of trace organic contaminants (TrOCs). The insufficient rejection of TrOCs such as endocrine disrupting compounds (EDCs) by polyamide membranes can jeopardize product water safety in wastewater reclamation. In this study, we report a novel nonpolyamide membrane chemistry using green tannic acid-iron (TA-Fe) complexes to remove TrOCs. The nanofiltration membrane formed at a TA-Fe molar ratio of 1:3 (TA-Fe3) had a continuous thin rejection layer of 10-30 nm in thickness, together with a water permeability of 5.1 Lm2-h-1bar-1 and a Na2SO4 rejection of 89.7%. Meanwhile, this membrane presented significantly higher rejection of EDCs (up to 99.7%) than that of polyamide membranes (up to 81.8%). Quartz crystal microbalance results revealed that the sorption amount of a model EDC, benzylparbaen, by TA-Fe3 layer was nearly 2 orders of magnitude less than that by polyamide, leading to reduced transmission and higher rejection. Further analysis of membrane revealed a much greater water/EDC selectivity of the TA-Fe3 membrane compared to the polyamide membranes.
Assuntos
Complexos de Coordenação , Purificação da Água , Membranas Artificiais , Nylons , PermeabilidadeRESUMO
A new green-emitting fluorescent probe 1 was developed for biothiol detection. The sensing mechanism was considered to be biothiol-induced cleavage of the 2,4-dinitrobenzene- sulfonate group in probe 1 and resulting inhibition of the probe's photoinduced electron transfer (PET) process. Probe 1 exhibited favorable properties such as excellent selectivity, highly sensitive (0.12 µM), large Stokes shift (117 nm) and a remarkable turn-on fluorescence signal (148-fold). Furthermore, confocal fluorescence imaging indicated that probe 1 was membrane-permeable and suitable for visualization of biothiols in living A549 cells.