RESUMO
Nitrogen fixation, occurring through the symbiotic relationship between legumes and rhizobia in root nodules, is crucial in sustainable agriculture. Nodulation and soybean production are influenced by low levels of phosphorus stress. In this study, we discovered a MADS transcription factor, GmAGL82, which is preferentially expressed in nodules and displays significantly increased expression under conditions of phosphate (Pi) deficiency. The overexpression of GmAGL82 in composite transgenic plants resulted in an increased number of nodules, higher fresh weight, and enhanced soluble Pi concentration, which subsequently increased the nitrogen content, phosphorus content, and overall growth of soybean plants. Additionally, transcriptome analysis revealed that the overexpression of GmAGL82 significantly upregulated the expression of genes associated with nodule growth, such as GmENOD100, GmHSP17.1, GmHSP17.9, GmSPX5, and GmPIN9d. Based on these findings, we concluded that GmAGL82 likely participates in the phosphorus signaling pathway and positively regulates nodulation in soybeans. The findings of this research may lay the theoretical groundwork for further studies and candidate gene resources for the genetic improvement of nutrient-efficient soybean varieties in acidic soils.
Assuntos
Fósforo , Nodulação , Fósforo/metabolismo , Nodulação/genética , Nódulos Radiculares de Plantas/metabolismo , Glycine max/genética , Fixação de Nitrogênio/genética , Simbiose , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Rhinacanthus nasutus (L.) Kurz is a traditional Chinese medicine in China. In August 2022, leaf spots were observed on R. nasutus in a Chinese herbal garden in Zhanjiang, Guangdong Province, China (21°17'30â³N, 110°18'25â³E). Disease incidence was 90% (n = 100 investigated plants from about 800 plants). The yellow spots were round, gray in the center and scattered on the leaves. The coalescence of the individual spot eventually led to leaf wilt. Ten symptomatic leaves from 10 plants were sampled. The margins of the samples were cut into 2 mm × 2 mm pieces. The tissue surface was disinfected with 75% ethanol for 30 s and 2% sodium hypochlorite for 60 s. Thereafter, the samples were rinsed three times in sterile water, placed on potato dextrose agar (PDA), and incubated at 28 °C. Pure cultures were obtained by transferring hyphal tips to new PDA plates. Twenty-eight isolates were obtained (isolation frequency = 28/4 × 10 = 70%). Three representative single-spore isolates (RNPO-1, RNPO-2, and RNPO-3) by a single-spore isolation method (Fang. 1998) were used for further study. The colonies of isolates on PDA were olive green in 7 days at 28 °C. Conidiogenous cells were unbranched, geniculate-sinuous, tapered toward the apex, and 10 to 20 × 3 µm (n = 20). Conidia were solitary, smooth, straight or curved, pale brown, 3 to 8-septate, apex acute, base truncate, and 50.5 to 88.5 × 2.0 to 3.5 µm (n = 50). For molecular identification, the colony PCR method with Taq DNA polymerase and MightyAmp DNA Polymerase (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS), translation elongation factor 1-α gene (TEF1), actin (ACT) , and RNA polymerase II second largest subunit (RPB2) loci of the isolates using primer pairs ITS1/ITS4, EF1/EF2, ACT-512F/ACT-783R, and RPB2-7CF/fRPB2-11aR, respectively (O'Donnell et al. 1998; O'Donnell et al. 2010). Their sequences were deposited in GenBank under nos. OP963568 to OP963570 (ITS), OP998376 to OP998378 (TEF1), OP998373 to OP998375 (ACT), and OP998379 to OP998381 (RPB2). By using the Maximum Likelihood method, a phylogenetic tree was generated on the basis of the concatenated data from the sequences of ITS, TEF1, ACT, and RPB2 that clustered the isolates with P. oenotherae (the type strain CBS 131920). The fungus was thus identified as P. oenotherae basing on these morphological and molecular characteristics (Guo and Liu. 1992; Kirschner. 2015). Pathogenicity testing was performed in a greenhouse with 80% relative humidity at 28 °C to 30 °C. Healthy plants of R. nasutus were grown in pots, with one plant in each pot. Sterile cotton balls were immersed in the spore suspension (1 × 105 per mL) of the isolates for about 15 s before they were adhered to the leaves for 3 days. Each isolate was inoculated with three plants (2 month old), and each plant was inoculated with five leaves. Sterile distilled water was as the control and same treatment. The test was performed three times. Symptom were found on the inoculated plants after 2 weeks with the disease incidence 100%, whereas the control plants remained healthy. The fungus was re-isolated from the infected leaves and confirmed as the same isolates by morphological and ITS analyses. No pathogen was isolated from the control plants. P. oenotherae caused leaf spot on Oenothera biennis L. (Guo and Liu. 1992). To the best of our knowledge, this is the first report that R. nasutus is the new host of P. oenotherae (Crous et al. 2013). Thus, this work provides an important reference for the control of this disease in the future.
RESUMO
Dendrobium huoshanense is a famous edible and medicinal herb, and polysaccharides are the main bioactive component in it. In this study, response surface methodology (RSM) combined with a Box-Behnken design (BBD) was used to optimize the enzyme-assisted extraction (EAE), ultrasound-microwave-assisted extraction (UMAE), and hot water extraction (HWE) conditions and obtain the polysaccharides named DHP-E, DHP-UM, and DHP-H. The effects of different extraction methods on the physicochemical properties, structure characteristics, and bioactivity of polysaccharides were compared. The differential thermogravimetric curves indicated that DHP-E showed a broader temperature range during thermal degradation compared with DHP-UM and DHP-H. The SEM results showed that DHP-E displayed an irregular granular structure, but DHP-UM and DHP-H were sponge-like. The results of absolute molecular weight indicated that polysaccharides with higher molecular weight detected in DHP-H and DHP-UM did not appear in DHP-E due to enzymatic degradation. The monosaccharide composition showed that DHPs were all composed of Man, Glc, and Gal but with different proportions. Finally, the glycosidic bond types, which have a significant effect on bioactivity, were decoded with methylation analysis. The results showed that DHPs contained four glycosidic bond types, including Glcp-(1â, â4)-Manp-(1â, â4)-Glcp-(1â, and â4,6)-Manp-(1â with different ratios. Furthermore, DHP-E exhibited better DPPH and ABTS radical scavenging activities. These findings could provide scientific foundations for selecting appropriate extraction methods to obtain desired bioactivities for applications in the pharmaceutical and functional food industries.
Assuntos
Antioxidantes , Dendrobium , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Dendrobium/química , Peso Molecular , Monossacarídeos/análise , Polissacarídeos/farmacologia , Polissacarídeos/químicaRESUMO
Ochratoxin A (OTA) is a common mycotoxin with high carcinogenicity; therefore, it is crucial to establish a simple, rapid, and sensitive method for its detection. In this study, we developed a "turn-on" fluorescence assay for detecting OTA based on guanine quenching of the aptamer. The method uses fluorescein (FAM) fluorophore to label the complementary strand of the OTA aptamer, Fc-DNA. In the absence of OTA, the Fc-DNA hybridizes with the aptamer to form a double strand. Due to the occurrence of photo-induced electron transfer (PET), the FAM fluorescence signal is quenched as the FAM on the Fc-DNA approaches the guanine of the aptamer at the 5' end. When OTA is present, the aptamer binds to it and thus, is unable to hybridize with Fc-DNA to form a double strand; the FAM fluorescence signal is restored as FAM moves away from the guanine of the aptamer. The assay achieved OTA detection at a detection limit of 28.4 nM. The application of the original guanine of the aptamer as the quenching agent helps avoid the complex designing and labeling of the aptamer, which ensures the high affinity of the aptamer for OTA. Meanwhile, this "turn-on" detection mode helps avoid potential false-positive results as in the "turn-off" mode and improves the assay's sensitivity. Additionally, the method has good selectivity and can be used to detect OTA in traditional Chinese medicine. This method provides a simple, low-cost, and rapid method for OTA detection.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Ocratoxinas , Limite de Detecção , Aptâmeros de Nucleotídeos/metabolismo , Ocratoxinas/análise , Corantes Fluorescentes , Técnicas Biossensoriais/métodosRESUMO
Whether gingival crevicular fluid (GCF) indexes in patients with severe periodontitis affect the efficacy of drug treatment was a new direction of recent research. At present, there were few studies on the effects of inflammatory indicators, BGP, and MMP-8 levels in GCF on the efficacy of drug treatment in such patients. So the purpose of this study was to observe the changes in osteocalcin (BGP), matrix metalloproteinase-8 (MMP-8), and inflammatory indexes levels in GCF of patients with severe periodontitis. The correlation between the above indexes and the effect of drug treatment in the patients was analyzed, in order to provide guidance for improving the clinical curative effect of severe periodontitis. A retrospective analysis was conducted to collect the baseline data of patients with severe periodontitis who were treated with Minocycline Hydrochloride Ointment in our hospital. The inflammatory indicators, BGP, and MMP-8 levels in GCF were analyzed before drug treatment, and the treatment effect on the patients was counted. Logistic regression was used to analyze the correlation between BGP, MMP-8, and inflammatory indicators levels in GCF and the drug treatment effect on the patients. After statistical analysis, we found that the response rate was 69% and the inefficiency was 31%. There were no significant differences in C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) levels between the inefficacy group and efficacy group (P > 0.05). Compared with the efficacy group, the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interleukin-8 (IL-8), BGP, and MMP-8 were increased in the inefficacy group. High levels of IL-6, IL-1ß, IL-8, BGP, and MMP-8 were associated with ineffective drug treatment in patients with severe periodontitis (all OR >1 and P < 0.05). Levels of IL-6, IL-1ß, IL-8, BGP, and MMP-8 predicted that the AUCs of drug treatment failure in patients with severe periodontitis were all greater than 0.7, which were 1.398, 1.458, 1.244, 1.012, and 1.012, respectively. From this, we can conclude that increased levels of BGP, MMP-8, and inflammatory indicators such as IL-6, IL-1ß, and IL-8 in GCF would increase the risk of ineffective drug treatment in patients with severe periodontitis. The clinical treatment plan could be adjusted according to the levels of the above indicators in GCF to improve the effectiveness of drug treatment in patients.
RESUMO
A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3',5,5'-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3',5,5'-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3',5,5'-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL-1 and a detection limit of 0.17 mU mL-1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.
Assuntos
Colorimetria , Pontos Quânticos , Acetilcolinesterase , Oxirredutases , FósforoRESUMO
BACKGROUND: Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. METHODS: We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. RESULTS: We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. CONCLUSION: For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.
Assuntos
Colina O-Acetiltransferase/metabolismo , Colinérgicos/farmacologia , Inflamação/prevenção & controle , Neoplasias Pancreáticas/tratamento farmacológico , Acetilcolina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Carrier-free nanotheranostics directly assembled by using clinically used photosensitizers and chemotherapeutic drugs are a promising alternative to tumor theranostics. However, the weak interaction-driven assembly still suffers from low structural stability against disintegration, lack of targeting specificity, and poor stimulus-responsive property. Moreover, almost all exogenous ligands possess no therapeutic effect. Enlightened by the concept of metal-organic frameworks, we developed a novel self-recognizing metal-coordinated nanotheranostic agent by the coordination-driven co-assembly of photosensitizer indocyanine green (ICG) and chemo-drug methotrexate (MTX, also served as a specific "targeting ligand" towards folate receptors), in which ferric (FeIII) ions acted as a bridge to tightly associate ICG with MTX. Such carrier-free metal-coordinated nanotheranostics with high dual-drug payload (â¼94 wt%) not only possessed excellent structural and physiological stability, but also exhibited prolonged blood circulation. In addition, the nanotheranostics could achieve the targeted on-demand drug release by both stimuli of internal lysosomal acidity and external near-infrared laser. More importantly, the nanotheranostics could self-recognize the cancer cells and selectively target the tumors, and therefore they decreased toxicity to normal tissues and organs. Consequently, the nanotheranostics showed strongly synergistic potency for tumor photo-chemotherapy under the precise guidance of magnetic resonance/photoacoustic/fluorescence imaging, thereby achieving highly effective tumor curing efficiency. Considering that ICG and bi-functional MTX are approved by the Food and Drug Administration, and FeIII ions have high biosafety, the self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics may hold potential applications in tumor theranostics.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Verde de Indocianina/farmacologia , Metotrexato/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Nanomedicina Teranóstica , Animais , Antimetabólitos Antineoplásicos/síntese química , Antimetabólitos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Verde de Indocianina/síntese química , Verde de Indocianina/química , Imageamento por Ressonância Magnética , Metotrexato/síntese química , Metotrexato/química , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Imagem Óptica , Tamanho da Partícula , Técnicas Fotoacústicas , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de SuperfícieRESUMO
Black phosphorus quantum dots (BP QDs) with small size are synthesized using an easy to operate thermal method. It was found that BP QDs possess oxidase-mimicking activity. They can catalyze the oxidation of the substrate 3,3',5,5'-tetramethylbenzidine to produce a blue-colored product even in the absence of hydrogen peroxide. Active oxygen species are proved to be involved in the reaction through the experiments of radical scavenging and electron spin resonance. Biothiols including reduced glutathione and cysteine inactivate the oxidase-mimicking activity of BP QDs, concomitant to the fading of the blue solution. This provides the base for a colorimetric method for the determination of glutathione and cysteine. The decreased absorbance at 652 nm displays linear response to the concentrations of glutathione ranging from 0.1 to 5.0 µmol L-1, and cysteine from 0.1 to 10.0 µmol L-1. The detection limits are 0.02 µmol L-1 and 0.03 µmol L-1 for glutathione and cysteine, respectively. Successive determinations of 1.0 µmol L-1 glutathione and 5.0 µmol L-1 cysteine solution give relative standard deviations of 0.8% and 1.7% (n = 11), respectively. As a preliminary application, the practicability of the method was evaluated by the determination of glutathione in pharmaceutical preparations. This work not only discovers a useful oxidase mimics but also sets up a reliable platform based on BP QDs in colorimetric detection. Graphical abstract Schematic representation of colorimetric determination for biothiols through inactivating oxidase mimetic-like catalytic activity of black phosphorus quantum dots (BP QDs) on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with dissolved oxygen to produce its blue oxidized product (oxTMB).
Assuntos
Técnicas Biossensoriais , Colorimetria , Cisteína/análise , Glutationa/análise , Oxirredutases/química , Fósforo/química , Pontos Quânticos/química , Cisteína/metabolismo , Glutationa/metabolismo , Estrutura Molecular , Oxirredutases/metabolismo , Fósforo/metabolismoRESUMO
In recent years, hepatitis B core protein virus-like particle (HBc VLP) is an impressive biomaterial, which has attracted considerable attention due to favorable properties such as structural stability, high uptake efficiency, and biocompatibility in biomedical applications. Heretofore, only a few attempts have been made to apply it in physical, chemical, and biological therapy for cancer. In this study, a tumor-targeting RGD-HBc VLP is first fabricated through genetic engineering. For image-guided cancer phototherapy, indocyanine green (ICG) is loaded into RGD-HBc VLP via a disassembly/reassembly pathway and electrostatic attraction with high efficiency. The self-assembled stable RGD-HBc VLP significantly improves body retention (fourfold longer), aqueous stability, and target specificity of ICG. Remarkably, these positive reformations promote more accurate and sensitive imaging of U87MG tumor, as well as prolonged tumor destruction in comparison with free ICG. Moreover, the photothermal and photodynamic effect on tumors are quantitatively differentiated by multiple linear regression analysis. Overall, less-potent medicinal ICG can be perfectly rescued by bioengineered HBc VLP to realize enhanced cancer optotheranostics.
Assuntos
Neoplasias , Hepatite B , Humanos , Verde de Indocianina , Fotoquimioterapia , FototerapiaRESUMO
BACKGROUND: Proximal humerus fractures are the third most common in the human body but their management remains controversial. Open reduction and internal fixation with plates is one of the leading modes of operative treatment for these fractures. The development of technologies and techniques for these plates, during the recent decades, promise a bright future for their clinical use. A comprehensive review of in vitro biomechanical studies is needed for the comparison of plates' mechanical performance and the testing methodologies. This will not only guide clinicians with plate selection but also with the design of future in vitro biomechanical studies. This review was aimed to systematically categorise and review the in vitro biomechanical studies of these plates based on their protocols and discuss their results. The technologies and techniques investigated in these studies were categorised and compared to reach a census where possible. METHODS AND RESULTS: Web of Science and Scopus database search yielded 62 studies. Out of these, 51 performed axial loading, torsion, bending and/or combined bending and axial loading while 11 simulated complex glenohumeral movements by using tendons. Loading conditions and set-up, failure criteria and performance parameters, as well as results for each study, were reviewed. Only two studies tested four-part fracture model while the rest investigated two- and three-part fractures. In ten studies, synthetic humeri were tested instead of cadaveric ones. In addition to load-displacement data, three-dimensional motion analysis systems, digital image correlation and acoustic emission testing have been used for measurement. CONCLUSIONS: Overall, PHILOS was the most tested plate and locking plates demonstrated better mechanical performance than non-locking ones. Conflicting results have been published for their comparison with non-locking blade plates and polyaxial locking screws. Augmentation with cement [calcium phosphate or poly(methyl methacrylate)] or allografts (fibular and femoral head) was found to improve bone-plate constructs' mechanical performance. Controversy still lies over the use of rigid and semi-rigid implants and the insertion of inferomedial screws for calcar region support. This review will guide the design of in vitro and in silico biomechanical tests and also supplement the study of clinical literature.
Assuntos
Placas Ósseas , Fenômenos Mecânicos , Fraturas do Ombro , Fenômenos Biomecânicos , HumanosRESUMO
To accomplish effective cancer imaging and integrated therapy, the multifunctional nanotheranostic Fe3O4-MTX@HBc core-shell nanoparticles (NPs) were designed. A straightforward method was demonstrated for efficient encapsulation of magnetic NPs into the engineered virus-like particles (VLPs) through the affinity of histidine tags for the methotrexate (MTX)-Ni2+ chelate. HBc144-His VLPs shell could protect Fe3O4-MTX NPs from the recognition by the reticuloendothelial system as well as could increase their cellular uptake efficiency. Through our well-designed tactic, the photothermal efficiency of Fe3O4 NPs were obviously improved in vitro and in vivo upon near-infrared (NIR) laser irradiation. Moreover, Magnetic resonance imaging (MRI) results showed that the Fe3O4-MTX@HBc core-shell NPs were reliable T2-type MRI contrast agents for tumor imaging. Hence the Fe3O4-MTX@HBc core-shell NPs may act as a promising theranostic platform for multimodal cancer treatment.
RESUMO
Tubomanometry (TMM) is a relatively novel method for testing the eustachian tube (ET) function, which is speculated to be closely related to otitis media with effusion (OME). The purpose of this study is to explore the predictive power of TMM value for medication outcomes in adult acute OME. A cohort of 41 adult acute OME patients with 53 affected ears was studied retrospectively. All these patients completed a 2-week treatment including oral Myrtol Standardized Enteric capsules, nasal steroid, and oral antihistamine. The results showed that the response rate was 41.5% (22/53). The ratio of tympanometry C and TMM value differed significantly between responders and non-responders (P < 0.05), and the TMM value is the only predictive variable for treatment outcomes (P < 0.001, odds ratio 1.873). A ROC analysis of the TMM value for the treatment outcome showed that the area under the curve could achieve 0.773 (P < 0.001), while the optimal cutoff value calculated by Youden index was 1.5, with 72.7% sensitivity and 74.2% specificity. The response rate of ears with 2-6 TMM values could reach 66.7% (16/24), which was significantly higher than that of ears with TMM values 0-1, 20.7% (6/29) (P < 0.001). These findings showed that acute OME patients with a high TMM value and tympanometry C of the affected ear could potentially benefit from medication. The TMM value was an independent predictive factor of the treatment outcomes that could guide treatment decisions.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Manometria/métodos , Monoterpenos/uso terapêutico , Otite Média com Derrame/diagnóstico , Testes de Impedância Acústica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Quimioterapia Combinada , Tuba Auditiva/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média com Derrame/tratamento farmacológico , Otite Média com Derrame/fisiopatologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto JovemRESUMO
Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor treatment often suffer from low fluorescence intensity and weak singlet oxygen generation efficiency, resulting in inadequate diagnostic and therapy efficacy for tumors. It is still a great challenge to improve both the photodynamic therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT) and FLI at a very low dosage of IR795 (0.4 µM) based on metal-enhanced fluorescence (MEF) effects. In our design, both the fluorescence intensity and reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the localized surface plasmon resonance band of AuNRs overlapping with the absorption or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to 82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence intensity of our designed nanocomposites was helpful to track their behavior in tumor cells. Therefore, our designed nanoagents highlight the applications of multimodal diagnostics and therapy in tumors based on MEF.
Assuntos
Alcinos/química , Corantes Fluorescentes/química , Hipertermia Induzida , Fotoquimioterapia , Fototerapia , Linhagem Celular Tumoral , Endocitose , Fluorescência , Ouro/química , Humanos , Nanotubos/química , Nanotubos/ultraestrutura , Dióxido de Silício/químicaRESUMO
This study reports a multifunctional nanoparticle (NP) that can be used for amplified magnetic resonance image (MRI)-guided photothermal therapy (PTT) due to its surface coating with a polydopamine (PDA) shell. Importantly, by means of introducing the surface coating of PDA, large quantities of water can be trapped around the NPs allowing more efficient water exchange, leading to greatly improved MR contrast signals compared with those from NPs without the PDA coating. Further, a distinct photothermal effect can be obtained arising from the strong absorption of PDA in the near-infrared (NIR) region. By synthesizing multifunctional MnCO3@PDA NPs, for example, we found that the longitudinal relaxivity (r1) of MnCO3 NPs can improve from 5.7 to 8.3 mM-1 s-1. Subsequently, in vitro MRI and PTT results verified that MnCO3@PDA could serve as an excellent MRI/PTT theranostic agent. Furthermore, the MnCO3@PDA NPs were applied as an MRI/PTT theranostic agent for in vivo MRI-guided photothermal ablation of tumors by intratumoral injection in 4T1 tumor-bearing mice. The MR imaging result shows a significantly bright MR image in the tumor site. The MnCO3@PDA-mediated PTT result shows high therapeutic efficiency as a result of high photothermal conversion efficiency. The present strategy of amplified MRI-guided PTT based on PDA coating of NPs will be widely applicable to other multifunctional NPs.
Assuntos
Nanopartículas , Animais , Carbonatos , Indóis , Imageamento por Ressonância Magnética , Manganês , Camundongos , Fototerapia , PolímerosRESUMO
We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects.
Assuntos
Implantes Absorvíveis , Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Regeneração Óssea , Alicerces Teciduais/química , Animais , Carga Bacteriana , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/microbiologia , Osso e Ossos/patologia , Bovinos , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Láctico/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanofibras/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Distribuição Aleatória , Vancomicina/uso terapêuticoRESUMO
A surface-enhanced Raman scattering (SERS)-assisted theranostic strategy was designed based on a synthesized multifunctional Fe3O4/Au cluster/shell nanocomposite. This theranostic strategy was used for free prostate specific antigen (free-PSA) detection, magnetic resonance imaging (MRI), and magnetic hyperthermia. The lowest protein concentration detected was 1ngmL(-1), and the limit of detection (LOD) of the calculated PSA was 0.75ngmL(-1). Then, MRI was carried out to visualize the tumor cell. Lastly, magnetic hyperthermia was employed and revealed a favorable killing effect for the tumor cells. Thus, this SERS-assisted strategy based on a Fe3O4/Au cluster/shell nanocomposite showed great advantages in theranostic treatment.
Assuntos
Meios de Contraste , Óxido Ferroso-Férrico , Ouro , Hipertermia Induzida , Magnetoterapia , Imageamento por Ressonância Magnética , Nanocompostos/química , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/farmacologia , Ouro/química , Ouro/farmacologia , HumanosRESUMO
PURPOSE: A preobject grid can reduce and correct scatter in cone beam computed tomography (CBCT). However, half of the signal in each projection is blocked by the grid. A synchronized moving grid (SMOG) has been proposed to acquire two complimentary projections at each gantry position and merge them into one complete projection. That approach, however, suffers from increased scanning time and the technical difficulty of accurately merging the two projections per gantry angle. Herein, the authors present a new SMOG approach which acquires a single projection per gantry angle, with complimentary grid patterns for any two adjacent projections, and use an interprojection sensor fusion (IPSF) technique to estimate the blocked signal in each projection. The method may have the additional benefit of reduced imaging dose due to the grid blocking half of the incident radiation. METHODS: The IPSF considers multiple paired observations from two adjacent gantry angles as approximations of the blocked signal and uses a weighted least square regression of these observations to finally determine the blocked signal. The method was first tested with a simulated SMOG on a head phantom. The signal to noise ratio (SNR), which represents the difference of the recovered CBCT image to the original image without the SMOG, was used to evaluate the ability of the IPSF in recovering the missing signal. The IPSF approach was then tested using a Catphan phantom on a prototype SMOG assembly installed in a bench top CBCT system. RESULTS: In the simulated SMOG experiment, the SNRs were increased from 15.1 and 12.7 dB to 35.6 and 28.9 dB comparing with a conventional interpolation method (inpainting method) for a projection and the reconstructed 3D image, respectively, suggesting that IPSF successfully recovered most of blocked signal. In the prototype SMOG experiment, the authors have successfully reconstructed a CBCT image using the IPSF-SMOG approach. The detailed geometric features in the Catphan phantom were mostly recovered according to visual evaluation. The scatter related artifacts, such as cupping artifacts, were almost completely removed. CONCLUSIONS: The IPSF-SMOG is promising in reducing scatter artifacts and improving image quality while reducing radiation dose.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Movimento (Física) , Imagens de Fantasmas , Análise de Regressão , Espalhamento de Radiação , Razão Sinal-RuídoRESUMO
Arthrobacter sp. YC-RL1, isolated from a petroleum-contaminated soil, is capable of degrading and utilizing a wide range of aromatic compounds for growth. Here we report the complete genome sequence of strain YC-RL1, which may facilitate the investigation of environmental bioremediation and provide new gene resources for biotechnology and gene engineering.
Assuntos
Arthrobacter/genética , Arthrobacter/isolamento & purificação , Genoma Bacteriano , Composição de Bases , Biodegradação Ambiental , Tamanho do Genoma , Petróleo/microbiologia , Microbiologia do Solo , Poluentes do SoloRESUMO
Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem. Herb-drug interactions have been extensively investigated worldwide, and there is an increasing concern about the clinical herb-drug interaction. In this review we introduced the current progress in the herb-drug interactions including evidence-based clinical studies and establishment of levels of evidence for herb-drug interaction; and in the related mechanisms including the induction and inhibition of metabolic enzymes, inhibition and induction of transport and efflux proteins, alteration of gastrointestinal functions, and alteration in renal elimination. We also analyzed both the achievements and the challenges faced in the concomitant administration of traditional Chinese medicine and western medicine.