RESUMO
BACKGROUND. Consensus is lacking regarding optimal embolic agents for transcatheter arterial embolization (TAE) of renal angiomyolipomas (AMLs). OBJECTIVE. The purpose of our study was to compare the safety and efficacy of TAE with polyvinyl alcohol (PVA) and TAE with a combination of ethiodized oil (Lipiodol)-bleomycin emulsion and N-butyl cyanoacrylate (NBCA)-Lipiodol emulsion for the treatment of patients with large or symptomatic AMLs. METHODS. This prospective study enrolled patients referred for TAE of a large (> 4 cm) or symptomatic renal AML from July 2007 to December 2018. Patients were randomized to undergo TAE using PVA particles or a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Patients underwent serial clinical follow-up visits and follow-up CT or MRI examinations after TAE. Outcomes were compared between groups. RESULTS. Seventy-eight patients were enrolled. After exclusions, the analysis included 72 patients (15 men, 57 women; mean age, 35.0 years; 51 patients with hematuria, 66 patients with flank pain): 35 patients were randomized to treatment by PVA and 37 were randomized to treatment by a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Complete occlusion of all angiographically visible arterial supply was achieved in all patients. No major adverse event occurred in any patient. The mean follow-up after TAE was 77 ± 45 (SD) months (range, 37-180 months). The frequency of resolution of hematuria after initial TAE without recurrence was greater after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 80.0%, respectively; p = .03). At 12-month follow-up, the frequency of complete resolution of flank pain was higher after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 75.0%, p = .03). Mean reduction in AML volume at 36 months or longer after TAE versus at baseline was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than in those treated by PVA (98.0% vs 85.7%, respectively; p = .04). The frequency of complete response by modified RECIST (mRECIST) criteria at 36 months or longer after TAE was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (94.6% vs 74.3%, p = .04). The rate of repeat TAE was higher among patients treated by PVA than among those treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion (25.7% vs 8.1%, p = .04). CONCLUSION. Superior outcomes after TAE of AML were achieved using Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than using PVA. CLINICAL IMPACT. TAE using a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion is a safe and effective treatment option for large or symptomatic AMLs. TRIAL REGISTRATION. Chinese Clinical Trial Registry ChiCTR2100053296.
Assuntos
Angiomiolipoma , Embolização Terapêutica , Embucrilato , Neoplasias Renais , Leucemia Mieloide Aguda , Masculino , Humanos , Feminino , Adulto , Óleo Etiodado/uso terapêutico , Bleomicina , Estudos Prospectivos , Álcool de Polivinil/uso terapêutico , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/terapia , Emulsões , Embucrilato/uso terapêutico , Dor no Flanco , Hematúria , Neoplasias Renais/terapia , Neoplasias Renais/tratamento farmacológico , Embolização Terapêutica/métodos , Resultado do Tratamento , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
The exploitation of specific guests which can respond to external stimuli is the main approach for the construction of stimuli-responsive supramolecular polymers (SPs) based on host-guest interactions. Most functional guests, however, fail to manifest stimuli-responses. Herein, a hypoxia-responsive dimeric azocalixarene (D-SAC4A) with outstanding hosting properties was used as the macrocyclic building block for the preparation of host stimuli-responsive SPs. Since azocalixarenes can also be compatible with stimuli-responsive guests, an antitumor drug, camptothecin (CPT), was chosen and linked via a disulfide-containing linker to afford a glutathione (GSH)-responsive ditropic guest (D-CPT). A unique dual-responsive SP was obtained by 1 : 1 mixing of D-SAC4A and D-CPT in water, which further assembled into SP nanoparticles (DSPNs). DSPNs displayed outstanding stability against dilution and biological interferants, as well as precise CPT-release under GSH and hypoxia conditions. In vitro and in vivo experiments demonstrated the good biosafety and tumor-suppressive effects of DSPNs.
Assuntos
Antineoplásicos , Polímeros , Antineoplásicos/farmacologiaRESUMO
The major diseases affecting the thoracic aorta are aneurysms and acute dissections, and pathogenic variants in 11 genes are confirmed to lead to heritable thoracic aortic disease. However, many families in which multiple members have thoracic aortic disease do not have alterations in the known aortopathy genes. Genes highly expressed in the aorta were assessed for rare variants in exome sequencing data from such families, and compound rare heterozygous variants (p.Pro45Argfs∗25 and p.Glu750∗) in LTBP3 were identified in affected members of one family. A homozygous variant (p.Asn678_Gly681delinsThrCys) that introduces an additional cysteine into an epidermal growth factor (EGF)-like domain in the corresponding protein, latent TGF-ß binding protein (LTBP-3), was identified in a second family. Individuals with compound heterozygous or homozygous variants in these families have aneurysms and dissections of the thoracic aorta, as well as aneurysms of the abdominal aorta and other arteries, along with dental abnormalities and short stature. Heterozygous carriers of the p.Asn678_Gly681delinsThrCys variant have later onset of thoracic aortic disease, as well as dental abnormalities. In these families, LTBP3 variants segregated with thoracic aortic disease with a combined LOD score of 3.9. Additionally, heterozygous rare LTBP3 variants were found in individuals with early onset of acute aortic dissections, and some of these variants disrupted LTBP-3 levels or EGF-like domains. When compared to wild-type mice, Ltbp3-/- mice have enlarged aortic roots and ascending aortas. In summary, homozygous LTBP3 pathogenic variants predispose individuals to thoracic aortic aneurysms and dissections, along with the previously described skeletal and dental abnormalities.
Assuntos
Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Predisposição Genética para Doença , Proteínas de Ligação a TGF-beta Latente/genética , Mutação/genética , Adulto , Idoso de 80 Anos ou mais , Animais , Pressão Sanguínea/genética , Feminino , Homozigoto , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , LinhagemRESUMO
As an unnecessary trace element, the content of aluminium in biological systems should be strictly controlled. Therefore, it was necessary to develop a convenient method for detection of aluminium ions. In this study, a fluorescent probe based on polythiophene derivatives was developed and used to detect Al3+ in Chinese traditional pasta. The fluorescence of this probe showed a significant decrease in hexamethylenetetramine-HCl buffer solution (pH 5) when Al3+ was present. In addition, the probe exhibited good sensitivity and selectivity to Al3+ over other metal ions when EDTA was used as the masking agent. Fluorescence intensity had a good linear relationship with the Al3+ concentration in the range 0.1-10 µM and the limit of detection for Al3+ was 39 nM. Furthermore, the probe was successfully applied to detect Al3+ in food samples and the results were consistent with ICP-AES.
Assuntos
Corantes Fluorescentes , Triticum , Ácidos Fosforosos , Polímeros , Espectrometria de Fluorescência , TiofenosRESUMO
Lysine (K) is an important target residue for protein and peptide delivery across membranes. K is the most frequently exposed residue in proteins, leading to high demand for the development of K-compatible transport activators. However, designing activators for K-rich peptides and proteins is more challenging than for arginine-rich species because of the kosmotropic nature of K and its recognition difficulty. In this study, we designed a new amphiphilic sulfonatocalix[5]arene (sCx5-6C) as a K-compatible transport activator. sCx5-6C was tailored with two key elements, recognition of K and the ability to embed into membranes. We measured the membrane transport efficiencies of α-poly-l-lysine, heptalysine, and histones across artificial membranes and of α-poly-l-lysine into live cells, activated by sCx5-6C. The results demonstrate that sCx5-6C acts as an efficient activator for translocating K-rich peptides and proteins, which cannot be achieved by known arginine-compatible activators.
Assuntos
Calixarenos/química , Lisina/metabolismo , Peptídeos/metabolismo , Proteínas/metabolismo , Ácidos Sulfônicos/química , Membrana Celular/metabolismo , Membranas Artificiais , Transporte ProteicoRESUMO
Cyclosporine-A (CsA) is a widely used immunosuppressant. In this study, we explore the pathway through which CsA suppressed the Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced increase in matrix metalloproteinase (MMP) activities in co-cultured human gingival fibroblasts (HGFs) and THP-1 monocytes. In the co-culture, we found that CsA inhibited the expression of cyclophilin A (CyPA), CD147 and the activities of MMPs, which were all induced by P.g-LPS. We also found that P.g-LPS and recombinant human CyPA increased activation of ERK1/2 and IκB (an NF-κB inhibitory protein), but CsA and the anti-CD147 antibody significantly inhibited these effects. Taken together, CsA in the presence of P.g-LPS might suppress MMP activities by blocking the CyPA/CD147 interaction that results in the inhibition of ERK1/2 and NF-κB signaling by interfering with the phosphorylation of ERK1/2 and IκB.
Assuntos
Ciclosporina/farmacologia , Fibroblastos/efeitos dos fármacos , Imunossupressores/farmacologia , Lipopolissacarídeos/farmacologia , Metaloproteinases da Matriz/metabolismo , Monócitos/efeitos dos fármacos , Basigina/metabolismo , Células Cultivadas , Técnicas de Cocultura , Ciclofilina A/metabolismo , Fibroblastos/metabolismo , Gengiva/citologia , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Porphyromonas gingivalis/metabolismo , Células THP-1RESUMO
Periodontitis, an oral inflammatory disease caused by periodontal pathogen infection, is the most prevalent chronic inflammatory disease and a major burden on healthcare. The TAM receptor tyrosine kinases (Tyro3, Axl and Mertk) and their ligands (Gas6 and Pros1) play a pivotal role in the resolution of inflammation and have been associated with chronic inflammatory and autoimmune diseases. In this study, we evaluated the effects of exogenous Pros1 in in vitro and in vivo models of periodontitis. We detected higher Pros1 but lower Tyro3 levels in inflamed gingival specimens of periodontitis patients compared with healthy controls. Moreover, Pros1 was mostly localized in the gingival epithelium of all specimens. In cultured human gingival epithelial cells (hGECs), Porphyromonas gingivalis LPS (p.g-LPS) stimulation down-regulated Pros1 and Tyro3. Exogenous Pros1 inhibited p.g-LPS-induced production of TNF-α, IL-6, IL-1ß, MMP9/2 and RANKL in a Tyro3-dependent manner as revealed by PCR, Western blot analysis, ELISA and gelatin zymography. Pros1 also restored Tyro3 expression down-regulated by p.g-LPS in hGECs. In rats treated with ligature and p.g-LPS, administration of Pros1 attenuated periodontitis-associated gingival inflammation and alveolar bone loss. Our mechanistic studies implicated SOCS1/3 and STAT1/3 as mediators of the in vitro and in vivo anti-inflammatory effects of Pros1. Collectively, the findings from this work supported Pros1 as a novel anti-inflammatory therapy for periodontitis.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Proteínas de Ligação ao Cálcio/metabolismo , Periodontite/prevenção & controle , Substâncias Protetoras/administração & dosagem , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT1/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adulto , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Animais , Infecções por Bacteroidaceae/complicações , Infecções por Bacteroidaceae/microbiologia , Proteínas de Ligação ao Cálcio/administração & dosagem , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Pessoa de Meia-Idade , Periodontite/etiologia , Periodontite/patologia , Porphyromonas gingivalis/patogenicidade , Proteína S , Ratos , Ratos Sprague-Dawley , Receptores Proteína Tirosina Quinases/genética , Fator de Transcrição STAT1/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto JovemRESUMO
The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescence-based method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host-dye reporter pair are encapsulated inside phospholipid vesicles. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host-dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.
Assuntos
Peptídeos Penetradores de Células/metabolismo , Fluorescência , Corantes Fluorescentes/metabolismo , Compostos Macrocíclicos/metabolismo , Lipossomas Unilamelares/metabolismo , Transporte Biológico , Peptídeos Penetradores de Células/química , Corantes Fluorescentes/química , Compostos Macrocíclicos/química , Microscopia de Fluorescência , Estrutura Molecular , Imagem Óptica , Lipossomas Unilamelares/químicaRESUMO
Rubber trees are the world's major source of natural rubber. Rubber-containing latex is obtained from the laticifer cells of the rubber tree (Hevea brasiliensis) via regular tapping. Rubber biosynthesis is a typical isoprenoid metabolic process in the laticifer cells; however, little is known about the positive feedback regulation caused by the loss of latex that occurs through tapping. In this study, we demonstrate the crucial role of jasmonate signalling in this feedback regulation. The endogenous levels of jasmonate, the expression levels of rubber biosynthesis-related genes, and the efficiency of in vitro rubber biosynthesis were found to be significantly higher in laticifer cells of regularly tapped trees than those of virgin (i.e. untapped) trees. Application of methyl jasmonate had similar effects to latex harvesting in up-regulating the rubber biosynthesis-related genes and enhancing rubber biosynthesis. The specific jasmonate signalling module in laticifer cells was identified as COI1-JAZ3-MYC2. Its activation was associated with enhanced rubber biosynthesis via up-regulation of the expression of a farnesyl pyrophosphate synthase gene and a small rubber particle protein gene. The increase in the corresponding proteins, especially that of farnesyl pyrophosphate synthase, probably contributes to the increased efficiency of rubber biosynthesis. To our knowledge, this is the first study to reveal a jasmonate signalling pathway in the regulation of rubber biosynthesis in laticifer cells. The identification of the specific jasmonate signalling module in the laticifer cells of the rubber tree may provide a basis for genetic improvement of rubber yield potential.
Assuntos
Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Hevea/fisiologia , Látex/biossíntese , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais , Genes Reporter , Hevea/genética , Filogenia , Técnicas do Sistema de Duplo-HíbridoRESUMO
Hevea brasiliensis is a key commercial source of natural rubber (cis 1,4-polyisoprene). In H. brasiliensis, rubber transferase is responsible for cis-1,4-polymerization of isoprene units from isopentenyl diphosphate and thus affects the yield of rubber. Little is known about the regulatory mechanisms of the rubber transferase gene at a molecular level. In this study we show that the 5'UTR intron of the promoter of the rubber transferase gene (HRT2) suppresses the expression of HRT2. A H. brasiliensis RING zinc finger protein (designated as HbRZFP1) was able to interact specifically with the HRT2 promoter to down-regulate its transcription in vivo. A 14-3-3 protein (named as HbGF14a) was identified as interacting with HbRZFP1, both in yeast and in planta. Transient co-expression of HbGF14a and HbRZFP1-encoding cDNAs resulted in HbRZFP1-mediated HRT2 transcription inhibition being relieved. HbGF14a repressed the protein-DNA binding of HbRZFP1 with the HRT2 promoter in yeast. We propose a regulatory mechanism by which the binding of HbGF14a to HbRZFP1 interferes with the interaction of HbRZFP1 with the HRT2 promoter, thereby repressing the protein-DNA binding between them. This study provides new insights into the role of HbGF14a in mediating expression of the rubber transferase gene in Hevea brasiliensis.
Assuntos
Proteínas 14-3-3/metabolismo , Regulação Enzimológica da Expressão Gênica , Hevea/metabolismo , Proteínas de Plantas/metabolismo , Transferases/genética , Proteínas 14-3-3/química , Proteínas 14-3-3/genética , Sequência de Aminoácidos , Regulação da Expressão Gênica de Plantas , Hevea/química , Hevea/classificação , Hevea/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Ligação Proteica , Domínios RING Finger , Borracha/metabolismo , Alinhamento de Sequência , Transferases/química , Transferases/metabolismo , Dedos de ZincoRESUMO
PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-µm and 100-µm polyvinyl alcohol (PVA) particles versus 100-µm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-µm plus 100-µm PVA particles (group A) or 100-µm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Qmax to < 7 mL/s. RESULTS: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Qmax (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group. CONCLUSIONS: PAE with 50-µm plus 100-µm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-µm PVA particles alone.
Assuntos
Embolização Terapêutica/métodos , Sintomas do Trato Urinário Inferior/terapia , Álcool de Polivinil/administração & dosagem , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Idoso , Idoso de 80 Anos ou mais , Pequim , Método Duplo-Cego , Embolização Terapêutica/efeitos adversos , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Microesferas , Pessoa de Meia-Idade , Álcool de Polivinil/efeitos adversos , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
Enzyme-responsive assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites at which the target enzymes are located. In this work, based on the concept of host-guest chemistry, a trypsin-responsive supramolecular vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural serine protease trypsin-cleavable cationic protein protamine as the guest molecule, is reported. The complexation of p-sulfonatocalix[4]arene with protamine directs the formation of a supramolecular binary vesicle, which is dissipated by trypsin with high selectivity. Therefore, the present system represents a principle-of-concept to build a controlled-release carrier at trypsin-overexpressed sites.
Assuntos
Benzenossulfonatos/química , Materiais Biocompatíveis/química , Calixarenos/química , Portadores de Fármacos/química , Compostos Macrocíclicos/química , Nanopartículas/química , Protaminas/química , Tripsina/química , Protaminas/metabolismo , Tensão Superficial , Tripsina/metabolismoRESUMO
Chiral variants of the prototypal metal-organic framework MOF-5, Λ-CMOF-5 and Δ-CMOF-5, have been synthesized by preparing MOF-5 in the presence of L-proline or D-proline, respectively. CMOF-5 crystallizes in chiral space group P213 instead of Fm3Ì m as exhibited by MOF-5. The phase purity of CMOF-5 was validated by single-crystal and powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, N2 adsorption, microanalysis, and solid-state vibrational circular dichroism. CMOF-5 undergoes a reversible single crystal-to-single crystal phase change to MOF-5 when immersed in a variety of organic solvents, although N-methyl-2-pyrrolidone (NMP) does not induce loss of chirality. Indeed, MOF-5 undergoes chiral induction when immersed in NMP, affording racemic CMOF-5.
Assuntos
Compostos Organometálicos/síntese química , Polímeros/síntese química , Compostos Organometálicos/química , Polímeros/química , Estereoisomerismo , Difração de Raios XRESUMO
CONSPECTUS: Developments in macrocyclic chemistry have led to supramolecular chemistry, a field that has attracted increasing attention among researchers in various disciplines. Notably, the discoveries of new types of macrocyclic hosts have served as important milestones in the field. Researchers have explored the supramolecular chemistry of several classical macrocyclic hosts, including crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Calixarenes represent a third generation of supramolecular hosts after cyclodextrins and crown ethers. Easily modified, these macrocycles show great potential as simple scaffolds to build podand-like receptors. However, the inclusion properties of the cavities of unmodified calixarenes are not as good as those of other common macrocycles. Calixarenes require extensive chemical modifications to achieve efficient endo-complexation. p-Sulfonatocalix[n]arenes (SCnAs, n = 4-8) are a family of water-soluble calixarene derivatives that in aqueous media bind to guest molecules in their cavities. Their cavities are three-dimensional and π-electron-rich with multiple sulfonate groups, which endow them with fascinating affinities and selectivities, especially toward organic cations. They also can serve as scaffolds for functional, responsive host-guest systems. Moreover, SCnAs are biocompatible, which makes them potentially useful for diverse life sciences and pharmaceutical applications. In this Account, we summarize recent work on the recognition and assembly properties unique to SCnAs and their potential biological applications, by our group and by other laboratories. Initially examining simple host-guest systems, we describe the development of a series of functional host-guest pairs based on the molecular recognition between SCnAs and guest molecules. Such pairs can be used for fluorescent sensing systems, enzymatic activity assays, and pesticide detoxification. Although most macrocyclic hosts prevent self-aggregation of guest molecules, SCnAs can induce self-aggregation. Researchers have exploited calixarene-induced aggregation to construct supramolecular binary vesicles. These vesicles respond to internal and external stimuli, including temperature changes, redox reactions, additives, and enzymatic reactions. Such structures could be used as drug delivery vehicles. Although several biological applications of SCnAs have been reported, this field is still in its infancy. Continued exploration of the supramolecular chemistry of SCnAs will not only improve the existing biological functions but also open new avenues for the use of SCnAs in the fields of biology, biotechnology, and pharmaceutical research. In addition, we expect that other interdisciplinary research efforts will accelerate developments in the supramolecular chemistry of SCnAs.
Assuntos
Calixarenos/química , Calixarenos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Nanopartículas/química , Fotoquimioterapia/métodos , Animais , Cátions , Ciclodextrinas/administração & dosagem , Ciclodextrinas/química , Humanos , Hidrogéis , Compostos Macrocíclicos/química , Micelas , Conformação Molecular , Poloxâmero/administração & dosagem , Rotaxanos/administração & dosagemRESUMO
Supramolecular polymeric vesicles are constructed by the complexation of p-sulfonatocalix[4]arene and chitosan, where the multivalent electrostatic interactions between the anionic sulfonate tetramer and cationic polyammoniums served as the dominant driving force. The supra-amphiphilic assemblies are disassembled upon exposure to a pH stimulus since the partial deprotonation of chitosan accompanied by a pH increase. Adding a competitive guest can also disrupt the assembly, representing the host-guest inclusion response. Interestingly, an abnormal temperature-response is observed, possibly as a result of the temperature-directed fusion process.
Assuntos
Quitosana/química , Polímeros/química , Calixarenos/química , Espectroscopia de Ressonância Magnética , Polímeros/síntese química , Eletricidade Estática , TemperaturaRESUMO
WRKY proteins constitute a large family of transcription factors. In this study, we identified 81 WRKY genes (named HbWRKY1 to HbWRKY81) in the latest rubber tree genome. Tissue-specific expression profiles showed that 74 HbWRKYs were expressed in at least one of the tissues and the other 7 genes showed very low expression in all tissues tested, which suggested that HbWRKYs took part in many cellular processes. The responses of 20 selected HbWRKYs to jasmonic acid (JA) and ethylene (ET) were analyzed in the latex. 17 HbWRKYs responded to at least one treatment, which included 15 HbWRKYs responding to JA treatment, 15 HbWRKYs to ET, which suggested that these HbWRKYs were regulated by JA and ET. We also observed that HbWRKY3, 14, and 55 bind HbSRPP promoter and activate the transcription in yeast. This study suggests that HbWRKY proteins maybe involved in the transcriptional regulation of nature rubber biosynthesis.
Assuntos
Genes de Plantas , Hevea/genética , Família Multigênica , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Látex/biossíntese , Dados de Sequência Molecular , Especificidade de ÓrgãosRESUMO
OBJECTIVE: To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. METHODS: The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and fourier transform infrared spectroscopy (FTIR), human umbilical cord mesenchymal stem cells (hUC-MSCs) culture and animal experiments. RESULTS: The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution. hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds (P>0.05). The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. CONCLUSION: The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.
Assuntos
Desenvolvimento Ósseo/fisiologia , Cartilagem/crescimento & desenvolvimento , Durapatita/química , Ácido Láctico/química , Ácido Poliglicólico/química , Alicerces Teciduais/química , Zeína/química , Animais , Materiais Biocompatíveis , Células Cultivadas , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Regeneração/fisiologia , Adulto JovemRESUMO
This article describes the physicochemical properties of chitosan-coated liposomes containing skin-protecting agents, coenzyme Q10 and alpha-lipoic acid (CCAL). CCAL had a spherical shell-core structure and liposomes inverted the surface charge from negative to positive after coating with chitosan. Compared with the uncoated liposome, CCAL had higher zeta potential, larger droplet size and long-term stability. Fourier transform infrared spectroscopy (FTIR) study showed that the driving force for chitosan coating the liposomes was enhanced via hydrogen bonding and ionic bond force between the chitosan and the alpha-lipoic acid. While the encapsulation efficiency (EE) of alpha-lipoic acid also increased by interacting with the chitosan shell. In vitro antioxidant activity study showed an excellent hydroxyl radical scavenging activity of CCAL. In vitro release study displayed a sustained drug release, and in vitro penetration studies promoted the accumulation of drugs in rabbit skin.
Assuntos
Quitosana , Materiais Revestidos Biocompatíveis , Sequestradores de Radicais Livres , Absorção Cutânea , Ácido Tióctico , Ubiquinona/análogos & derivados , Administração Cutânea , Animais , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacocinética , Sequestradores de Radicais Livres/farmacologia , Lipossomos , Coelhos , Ácido Tióctico/química , Ácido Tióctico/farmacocinética , Ácido Tióctico/farmacologia , Ubiquinona/química , Ubiquinona/farmacocinética , Ubiquinona/farmacologiaRESUMO
Ferroelectric polymers have recently attracted tremendous research interest due to their potential application in various emerging flexible devices. Nanostructured ferroelectric polymer materials, such as nanorods, nanotube, and nanowires, are essential for miniaturization of the relevant electronic components. More importantly, their improved sensitivity and functionality may be used to enhance the performance of existing devices or to develop and design new devices. In this article, the recently developed methods for fabricating ferroelectric polymer nanostructures are briefly reviewed. In particular, the distinct crystallization behaviors confined at the nanometer scale, the nanoconfinement induced structural change, their influence on the physical properties of the ferroelectric polymer nanostructures, and the possible underlying mechanisms are discussed.
Assuntos
Cristalização/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Polímeros/química , Módulo de Elasticidade , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície , Resistência à TraçãoRESUMO
Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.