RESUMO
The detection of virus RNA in wastewater has been established as a valuable method for monitoring Coronavirus disease 2019. Carbon nanomaterials hold potential application in separating virus RNA owing to their effective adsorption and extraction capabilities. However, carbon nanomaterials have limited separability under homogeneous aqueous conditions. Due to the stabilities in their nanostructure, it is a challenge to efficiently immobilize them onto magnetic beads for separation. Here, we develop a porous agarose layered magnetic graphene oxide (GO) nanocomposite that is prepared by agglutinating ferroferric oxide (Fe3O4) beads and GO with agarose into a cohesive whole. With an average porous size of approximately 500 nm, the porous structure enables the unhindered entry of virus RNA, facilitating its interaction with the surface of GO. Upon the application of a magnetic field, the nucleic acid can be separated from the solution within a few minutes, achieving adsorption efficiency and recovery rate exceeding 90% under optimized conditions. The adsorbed nucleic acid can then be preserved against complex sample matrix for 3 days, and quantitatively released for subsequent quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection. The developed method was successfully utilized to analyze wastewater samples obtained from a wastewater treatment plant, detecting as few as 10 copies of RNA molecules per sample. The developed aMGO-RT-qPCR provides an efficient approach for monitoring viruses and will contribute to wastewater-based surveillance of community infections.
Assuntos
Grafite , Nanocompostos , RNA Viral , Sefarose , Águas Residuárias , Grafite/química , Águas Residuárias/virologia , Águas Residuárias/química , RNA Viral/análise , RNA Viral/isolamento & purificação , Sefarose/química , Nanocompostos/química , Porosidade , AdsorçãoRESUMO
Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. The test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPEP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. This review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPEP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results.
RESUMO
Anion exchange is recognized as an effective method to regulate the composition, electronic conductivity, and electrochemical behavior of the transition metal-based compounds. In this work, anion exchange is adopted as a rational post-treatment route to facilitate the capacitive activity of CoNi2 S4 nanoparticle arrays grown on carbon cloth (CC) with high mass-loading. As soaked in saturated Na2 S solution, the CoNi2 S4 /CC electrode showed an increased capacity from 483â C g-1 to 841â C g-1 at 10â mA cm-2 with excellent rate performance and stable cycling performance, which was superior to the CoNi2 S4 /CC electrode activated by NaBH4 reduction. Anion exchange was beneficial for enhancing the crystallinity, retaining the adhesion of nanoarrays, and realizing low resistance nature in a mild route. The as-assembled CoNi2 S4 /CC//activated CC hybrid supercapacitor delivered a high areal capacitance of 1.28â F cm-2 at 5â mA cm-2 , and achieved an energy density of 0.58â mWh cm-2 at a power density of 4.5â mW cm-2 with excellent cycle stability with 90.6 % capacity retention after 10000 cycles.
RESUMO
In this paper, the vinyl-pyridine group was used to modify the BODIPY dimer photosensitizer (T-BDP2) to obtain a VP-BDP2 photosensitizer. Compared with the T-BDP2 photosensitizer, the VP-BDP2 photosensitizer could work under pure water conditions, the singlet oxygen yield was increased from 9.38% to 22.2%, the charge transfer rate was increased from about 30 ps to about 10 ps, and the red emission was enhanced in fluorescence imaging. In addition, the VP-BDP2 photosensitizer could also generate the superoxide radical (O2Ë-) under pure water conditions. The ROS generation mechanism of the VP-BDP2 photosensitizer was considered to be the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism, which was verified by fs-transient absorption spectra and theoretical calculation. In the photodynamic therapy of A-549 cells, the VP-BDP2 photosensitizers could generate singlet oxygen and superoxide radicals (O2Ë-) under biological conditions, and showed high phototoxicity with the IC50 value at 12.1 µM under light at 525 nm. Additionally, the multiple dipolar configuration meant that the VP-BDP2 photosensitizer could be used in two-photon fluorescence zebrafish imaging under 800 nm excitation, which sets the stage for future two-photon photodynamic therapy.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete , Peixe-Zebra , Polímeros , Alcenos , Superóxidos , Água , Piridinas/farmacologiaRESUMO
As one of the representative models in the field of image generation, generative adversarial networks (GANs) face a significant challenge: how to make the best trade-off between the quality of generated images and training stability. The U-Net based GAN (U-Net GAN), a recently developed approach, can generate high-quality synthetic images by using a U-Net architecture for the discriminator. However, this model may suffer from severe mode collapse. In this study, a stable U-Net GAN (SUGAN) is proposed to mainly solve this problem. First, a gradient normalization module is introduced to the discriminator of U-Net GAN. This module effectively reduces gradient magnitudes, thereby greatly alleviating the problems of gradient instability and overfitting. As a result, the training stability of the GAN model is improved. Additionally, in order to solve the problem of blurred edges of the generated images, a modified residual network is used in the generator. This modification enhances its ability to capture image details, leading to higher-definition generated images. Extensive experiments conducted on several datasets show that the proposed SUGAN significantly improves over the Inception Score (IS) and Fréchet Inception Distance (FID) metrics compared with several state-of-the-art and classic GANs. The training process of our SUGAN is stable, and the quality and diversity of the generated samples are higher. This clearly demonstrates the effectiveness of our approach for image generation tasks. The source code and trained model of our SUGAN have been publicly released.
RESUMO
OBJECTIVES: An accurate and rapid diagnosis is crucial for the appropriate treatment of pulmonary tuberculosis (TB). This study aims to develop an artificial intelligence (AI)-based fully automated CT image analysis system for detection, diagnosis, and burden quantification of pulmonary TB. METHODS: From December 2007 to September 2020, 892 chest CT scans from pathogen-confirmed TB patients were retrospectively included. A deep learning-based cascading framework was connected to create a processing pipeline. For training and validation of the model, 1921 lesions were manually labeled, classified according to six categories of critical imaging features, and visually scored regarding lesion involvement as the ground truth. A "TB score" was calculated based on a network-activation map to quantitively assess the disease burden. Independent testing datasets from two additional hospitals (dataset 2, n = 99; dataset 3, n = 86) and the NIH TB Portals (n = 171) were used to externally validate the performance of the AI model. RESULTS: CT scans of 526 participants (mean age, 48.5 ± 16.5 years; 206 women) were analyzed. The lung lesion detection subsystem yielded a mean average precision of the validation cohort of 0.68. The overall classification accuracy of six pulmonary critical imaging findings indicative of TB of the independent datasets was 81.08-91.05%. A moderate to strong correlation was demonstrated between the AI model-quantified TB score and the radiologist-estimated CT score. CONCLUSIONS: The proposed end-to-end AI system based on chest CT can achieve human-level diagnostic performance for early detection and optimal clinical management of patients with pulmonary TB. KEY POINTS: ⢠Deep learning allows automatic detection, diagnosis, and evaluation of pulmonary tuberculosis. ⢠Artificial intelligence helps clinicians to assess patients with tuberculosis. ⢠Pulmonary tuberculosis disease activity and treatment management can be improved.
Assuntos
Inteligência Artificial , Tuberculose Pulmonar , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Tuberculose Pulmonar/diagnóstico por imagemRESUMO
An efficient I2-promoted one-pot one-step three-component reaction for the synthesis of sulfhydryl indolizines from methyl ketones, 2-pyridylacetate derivatives, and sulfonyl hydrazides via an in situ cyclization-rethiolation strategy has been developed. This protocol shows excellent substrate compatibility, including for chain and cyclic aliphatic methyl ketones, natural product pregnenolone acetate, and phosphorus-containing methyl ketones, affording a series of valuable aliphatic-substituted indolizines in good yields.
Assuntos
Indolizinas , Ciclização , Cetonas , AcetonaRESUMO
A facile synthetic protocol for the preparation of spiro diheterocycles from easily available 2'-aminoacetophenones, isocyanates and 1,4-benzoquinones or quinone monoimines under mild conditions has been developed. This multi-component transformation is characterized by efficient construction of two heterocycles and one valuable quaternary carbon in one pot via an in situ cyclization-respiroannulation strategy. Moreover, this reaction showed a broad substrate scope, and generated diverse five-membered oxaspiros.
Assuntos
Isocianatos , Estrutura Molecular , CiclizaçãoRESUMO
BACKGROUND: Optimum cultivation and management measures are needed to increase the phosphorus (P) absorption efficiency of crops for sustainable agricultural production. Previous studies indicated that leguminous crops can promote P absorption by neighboring gramineous crops. In this study, we isolated and screened the phosphate-solubilizing bacteria (PSB) from soybean rhizosphere under a maize-soybean intercropping system in Southwest China, and nine PSBs with high P-solubilizing ability were identified. RESULTS: 16S rDNA sequencing and phylogenetic analysis showed that these PSBs belong mainly to Bacillus and Pseudomonas. The phosphate solubility of Bacillus aryabhattai B8W22 reached 388.62 µg mL-1 . High-performance liquid chromatographic analysis showed that each strain could secrete a large quantity of organic acids, including oxalic acid, malonic acid, citric acid and succinic acid. In addition, all strains produced indole acetic acid (IAA) and siderophores that could promote plant growth. Seed germination experiments testified that PSBs isolated in this study have an innate ability to promote plant growth. The plant culture pot experiment further illustrated that soil acid phosphatase (ACP) activity and available P content, as well as plant P uptake, increased significantly with PSBs inoculation. CONCLUSION: PSBs from the rhizosphere soil of intercropped soybean could secrete organic acids that increase the solubilization of unavailable P, improve soil ACP activity and P availability, and produce IAA and siderophores that promote maize seed germination and seedling growth. Our findings indicate the PSBs from soybean rhizosphere have significant potential to reduce the application of chemical phosphate fertilizers and to promote sustainable agricultural development. © 2021 Society of Chemical Industry.
Assuntos
Fosfatos , Rizosfera , Bactérias , Filogenia , Microbiologia do Solo , Glycine max , Zea maysRESUMO
OBJECTIVE: To investigate the effect and mechanism of piceatannol on cerebral ischemia-reperfusion injury. METHODS: The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in primary cultured suckling rat cortical neuron cells. After 2â h of oxygen-glucose deprivation, the cells were treated with piceatannol for 24â h. The cell survival rate was detected by MTT assay, and the degree of cell damage was detected by intracellular lactate dehydrogenase (LDH) release assay. The activity of superoxide dismutase (SOD) and the content of adenosine triphosphate (ATP) were detected by colorimetric method. The content of reactive oxygen species (ROS) was detected by flow cytometry or observed with inverted fluorescence microscope. The ultrastructure of mitochondria was observed with transmission electron microscopy. Western blotting was used to detect the phosphorylation levels of protein kinase B (AKT) and glycogen synthase kinase (GSK)-3ß. Immunofluorescence staining was used to observe the nuclear localization of nuclear factor-erythroid 2-related factor (Nrf) 2. After OGD/R neuron cells were pretreated with Nrf2 inhibitor ML385 for 24â h, the effect of Nrf2 on the improvement of cell activity and antioxidant activity of piceatannol were investigated. Western blotting was used to detect the protein expression levels of Nrf2, heme oxygenase (HO) 1 and NADPH quinone oxidoreductase (NQO) 1. RESULTS: Piceatannol significantly increased the survival rate of OGD/R neurons, decreased LDH release and reactive oxygen species content, increased SOD activity, ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and ATP level (all P<0.05), increased phosphorylation of AKT and GSK-3ß protein, up-regulated the expression of Nrf2, HO-1 and NQO1 protein, increased the nuclear-to-plasma ratio of Nrf2, and promoted the nuclear transfer of Nrf2 (all P<0.05). ML385 could significantly reverse the rescue effect of paclitaxel on the model cells and the regulatory activities of SOD, ROS and LDH (all P<0.05). CONCLUSION: Piceatannol can regulate Nrf2 by activating GSK-3ß signaling pathway, promote its nuclear translocation, exert corresponding antioxidant effect, and protect mitochondrial structure and function in rat neuron cells.
Assuntos
Oxigênio , Traumatismo por Reperfusão , Ratos , Animais , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Glucose/metabolismo , Glucose/farmacologia , Transdução de Sinais , Neurônios , Superóxido Dismutase , Estresse OxidativoRESUMO
OBJECTIVE: To investigate the effect and mechanism of Pinus massoniana needle extracts (PNE) on oxidative stress injury in cerebral ischemia reperfusion rats. METHODS: The SD male rats were randomly divided into sham group, model control group, Edaravone (3â mg/kg) group, PNE low-dose (200â mg/kg), medium-dose (400â mg/kg) and high-dose (800â mg/kg) groups. PNE was administered by gavage for 7â d before modeling and 6â h after modeling in PNE treatment groups; Edaravone was given by intraperitoneal injection 7â d before modeling and 6â h after reperfusion. The rat model of cerebral ischemia reperfusion injury was established by middle cerebral artery occlusion method. After 24â h of reperfusion, the neurological deficit score, brain water content and cerebral infarction volume of rats were measured. The pathological changes of cerebral cortex and hippocampus were observed by HE staining, and the number of normal nerve cells was counted. The apoptosis rate of neurons in cerebral cortex was detected by TUNEL method. The content of nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) activity in ischemic brain tissue were detected. The protein expression of c-Jun N-terminal kinase (JNK) 3, phosphorylated JNK3 (p-JNK3), B-cell lymphoma protein(Bcl) -2, Bcl-2 associated X (Bax), cytochrome C and caspase-3 in cerebral cortex were detected by Western blotting method. RESULTS: Compared with the model control group, the behavioral score, brain water content and cerebral infarction volume in PNE groups were significantly reduced (all P<0.05), the pathological damage of cerebral cortex and hippocampal CA1 area was significantly alleviated, and the number of normal nerve cells in ischemic cortex and hippocampal CA1 area was increased (all P<0.05). The medium-dose PNE group had the best effect. Compared with the model control group, the apoptosis rate of cortical neurons, the content of NO and MDA in cerebral cortex, the ratio of p-JNK3/JNK3, the expression level of cytochrome C and caspase-3 protein in PNE medium-dose group were significantly reduced , and the activity of SOD, the Bcl-2/Bax ratio were significantly improved (all P<0.05). CONCLUSION: PNE ameliorates brain injury after cerebral ischemia reperfusion in rats, which may be related to scavenging NO and MDA, inhibiting oxidative stress-mediated JNK3/caspase-3 signsal transduction to inhibit neuronal apoptosis.
Assuntos
Isquemia Encefálica , Estresse Oxidativo , Extratos Vegetais , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Apoptose , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Proteína X Associada a bcl-2/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Caspase 3/metabolismo , Caspase 3/farmacologia , Citocromos c/metabolismo , Citocromos c/farmacologia , Citocromos c/uso terapêutico , Edaravone/farmacologia , Edaravone/uso terapêutico , Infarto da Artéria Cerebral Média , Ratos Sprague-Dawley , Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Superóxido Dismutase , Extratos Vegetais/farmacologia , Pinus/químicaRESUMO
Piceatannol is a natural plant-derived compound with protective effects against cardiovascular diseases. However, its effect on cerebral ischaemia-reperfusion injury (CIRI) induced by oxidative stress remains unclear. This study aimed to investigate piceatannol's antioxidation in CIRI. An in vitro oxygen-glucose deprivation followed by reoxygenation model was used and cell viability was measured. A middle cerebral artery occlusion followed by reperfusion model was used in vivo. Neurological function, encephalisation quotient, oedema, and volume of the cerebral infarction were then evaluated. The effects of piceatannol on histopathological findings, as well as the ultrastructure of the cortex, were analysed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lactate dehydrogenase (LDH) and the malondialdehyde (MDA) content was measured both in vitro and in vivo. Finally, the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) in cerebral tissue was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results demonstrated that cell viability in the piceatannol groups was increased. The SOD, GSH-Px activities were increased as LDH activity and MDA content decreased in the piceatannol groups both in vitro and in vivo, reflecting a decrease in oxidative stress. The neurological severity score and infarction volume in the piceatannol groups at doses of 10 and 20 mg/kg were lower than those of the model group. Furthermore, the damage seen on histopathological examination was partially attenuated by piceatannol. RT-qPCR and western blot analysis indicated that the expression of Nrf2, HO-1, and NQO1 were significantly increased by piceatannol. The results of the study demonstrate that piceatannol exerts a protective effect against CIRI.
Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Estilbenos/uso terapêutico , Animais , Encéfalo/patologia , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Glucose/deficiência , Heme Oxigenase-1/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Impaired cochlear blood perfusion and microvascular damage can cause sudden sensorineural hearing loss (SSHL), which is a potential risk factor for dementia. This study explored the association between SSHL and dementia. METHODS: This retrospective cohort study used a random sample of 1000,000 individuals from Taiwan's National Health Insurance Research Database. We identified 3725 patients newly diagnosed with SSHL between January 1, 2000, and December 31, 2009, and propensity score matching according to age, sex, index year, comorbidities, and medications was used to select the comparison group of 11,175 patients without SSHL. Participants were stratified by age (<65 and â§65 years) and sex for the subgroup analyses. The outcome of interest was all cause dementia (ICD-9-CM codes 290.0, 290.4, 294.1, 331.0). Both groups were followed up until December 31, 2010, for diagnoses of dementia. Cox regression models were used to estimate the hazard ratio (HR) of dementia. RESULTS: During the average 5-year follow-up period, the incidence rate of dementia in the SSHL cohort was 6.5 per 1000 person-years compared with 5.09 per 10,000 person-years in the comparison group. After adjustment for potential confounders, patients with SSHL were 1.39 times more likely to develop dementia than those without SSHL (95% confidence interval = 1.13-1.71). When stratified by patients' age and sex, the incidence of dementia was 1.34- and 1.64-fold higher in patients with SSHL aged ≥65 years (P = .013) and in women (P = .001), respectively, compared with the comparison group. Women with SSHL who were < 65 years old had the highest risk (2.14, 95% CI = 1.17-4.11, P = .022). In addition, a log-rank test revealed that patients with SSHL had significantly higher cumulative incidence of dementia than those without SSHL (P = .002). CONCLUSIONS: Patients with SSHL, especially women aged < 65 years, were associated with higher risk of dementia than those without SSHL. Thus, clinicians managing patients with SSHL should be aware of the increased risk of dementia.
Assuntos
Demência/epidemiologia , Demência/etiologia , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Súbita/complicações , Adulto , Idoso , Estudos de Coortes , Comorbidade , Feminino , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Súbita/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Nitritation facilitates the application of anaerobic ammonium oxidation (Anammox)-based processes for cost-efficient nitrogen removal from wastewater. This study proposed light irradiation as a novel strategy to rapidly start up nitritation by stimulating both the activities and growth of ammonia-oxidizing bacteria (AOB) while suppressing that of nitrite-oxidizing bacteria (NOB). Batch assays and kinetic model jointly suggested that AOB activity presented an initial increase followed by a decline while NOB decreased continuously throughout the light energy densities applied. Under optimal light energy densities (0.03-0.08 kJ/mg VSS), the highest nitrite accumulation ratio of 70.0% was achieved in sequencing batch reactors with both mainstream online and sidestream offline light treatments when treating real or synthetic municipal wastewater. Light irradiation induced different responses of AOB and NOB, leading to microbial structure optimization. Specifically, the expression of nxrB was downregulated, while the expression of amoA was upregulated under appropriate light irradiation. Moreover, although Nitrosomonas as typical AOB disappeared, the family Nitrosomonadaceae was doubled with enrichment of Ellin6067 and another four Nitrosomonadaceae genera that were only identified in light-treated reactors, thus ensuring AOB predominance and stable nitritation. These findings offer a new approach to rapidly establishing nitritation using light irradiation in municipal wastewater, especially for nitritation/microalgae system.
Assuntos
Amônia , Compostos de Amônio , Bactérias/genética , Reatores Biológicos , Expressão Gênica , Nitritos , Nitrogênio , Oxirredução , EsgotosRESUMO
The increased incidence of chronic cutaneous wounds is likely to lead to increased mortality, and therefore, deserves greater attention. More insight is needed into the magnitude of the problem of chronic cutaneous wounds and methods for their prevention and treatment in China. A retrospective analysis of data retrieved from an electronic health-records database on 3300 patients with chronic skin wounds was conducted from 1 January 2018 to 31 December 2018. The patients had been admitted to the medical and surgical wards of 17 third-grade class-A hospitals in China. The study's aim was to compare the characteristics (eg, demographic and clinical) associated with different causes and distributions of patients' chronic wounds. Among the 3300 patients, 66.03% were males and 33.97% were females. The mean age was 57 years and the increasing prevalence of chronic skin wounds with aging was quite high. The primary causes of chronic wounds were diabetes or infection, followed by pressure ulcers, trauma, and iatrogenic wounds. The distribution of skin wounds was mainly in the lower extremities (56.1%), followed by the trunk (18.6%). The mean duration of hospital stay was 29 days and the mean recurrence was 3 months. Chronic skin wounds were related to occupation, educational level, lifestyle habits, and income. The main cause of chronic skin wounds has shifted from trauma to chronic disease. Normalization checks, bacterial cultures, and antibiotic use in China need to be standardized and the training of wound specialists should be further strengthened. The association of aging and wound infection was significant. Preventive management and efficient treatment should correspond to the needs of the different regions of China. These results may serve as a reference for other developing countries in their transitional development.
Assuntos
Pacientes Internados , Lesões dos Tecidos Moles/epidemiologia , Adulto , Idoso , China/epidemiologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe2+ are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1ß, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis.
Assuntos
Benzilisoquinolinas/química , Calixarenos/química , Hemorragia Cerebral/patologia , Portadores de Fármacos/química , Metais/química , Nanoestruturas/química , Fármacos Neuroprotetores/química , Fenóis/química , Tetra-Hidroisoquinolinas/química , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Interleucina-1beta/metabolismo , Íons/química , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Organofosfonatos/química , Espécies Reativas de Oxigênio/metabolismo , Tetra-Hidroisoquinolinas/administração & dosagem , Tetra-Hidroisoquinolinas/farmacologiaRESUMO
Prolonged treatment with cisplatin (CDDP) frequently develops chemoresistance. We have previously shown that p22phox, an endoplasmic reticulum (ER) membrane protein, confers CDDP resistance by blocking CDDP nuclear entry in oral squamous cell carcinoma (OSCC) cells; however, the underlying mechanism remains unresolved. Using a fluorescent dye-labeled CDDP, here we show that CDDP can bind to p22phox in both cell-based and cell-free contexts. Subsequent detection of CDDP-peptide interaction by the Tris-Tricine-based electrophoresis revealed that GA-30, a synthetic peptide matching a region of the cytosolic domain of p22phox, could interact with CDDP. These results were further confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis, from which MA-11, an 11-amino acid subdomain of the GA-30 domain, could largely account for the interaction. Amino acid substitutions at Cys50, Met65 and Met73, but not His72, significantly impaired the binding between CDDP and the GA-30 domain, thereby suggesting the potential CDDP-binding residues in p22phox protein. Consistently, the p22phox point mutations at Cys50, Met65 and Met73, but not His72, resensitized OSCC cells to CDDP-induced cytotoxicity and apoptosis. Finally, p22phox might have binding specificity for the platinum drugs, including CDDP, carboplatin and oxaliplatin. Together, we have not only identified p22phox as a novel CDDP-binding protein, but further highlighted the importance of such a drug-protein interaction in drug resistance.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , NADPH Oxidases/metabolismo , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Apoptose , Carboplatina/administração & dosagem , Carboplatina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Cisplatino/administração & dosagem , Cisplatino/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , NADPH Oxidases/genética , Oxaliplatina/administração & dosagem , Oxaliplatina/metabolismo , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the regulatory effect of iridoid glycoside of radix scrophulariae (IGRS) on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion in vitro model. METHODS: Rat pheochromocytoma PC12 cells were pretreated with IGRS (50, 100, 200 µg/mL) for 24h, and the in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) was applied. The cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The apoptotic rate was detected by flow cytometry. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C/EBP homologous protein (CHOP), caspase-12 protein, and glucose-regulated protein-78(GRP78)were detected by Western blotting. The mRNA expression levels of sarco/endoplasmic reticulum Ca2+-ATPase2 (SERCA2), 1, 4, 5-triphosphate inositol receptor 1 (IP3R1), and ryanodine receptor 2 (RyR2)were detected by real-time RT-PCR. Free Ca2+ concentration [Ca2+]i was determined by using laser scanning confocal microscopy. RESULTS: The damage caused by OGD/R to PC12 cells was significantly reduced by IGRS, with significant effect on increasing survival rate and reducing LDH release (all P<0.01). The expression of GRP78, CHOP, Bax, and caspase-12 were down-regulated (all P<0.01), and the expression of Bcl-2 and Bcl-2/Bax ratio was up-regulated (all P<0.01); IGRS increased the expression of SERCA2 mRNA in PC12 cells after OGD/R injury (P<0.01), decreased [Ca2+]i and down-regulated the expression of RyR2 mRNA and IP3R1 mRNA. CONCLUSIONS: IGRS has neuroprotective effect, which may alleviate cerebral ischemia-reperfusion injury by regulating SERCA2, maintaining calcium balance, and inhibiting endoplasmic reticulum stress-mediated apoptosis.
Assuntos
Estresse do Retículo Endoplasmático , Glicosídeos Iridoides , Traumatismo por Reperfusão , Caramujos , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucose , Técnicas In Vitro , Glicosídeos Iridoides/farmacologia , Oxigênio , Células PC12 , Ratos , Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Caramujos/químicaRESUMO
OBJECTIVE: To explore the healing effect on wound after transplanting sheep acellular dermal matrix (ADM) microparticle together with autoallergic skin microparticle.â© Methods: The rats were divided into three groups. Full-thickness skin wound at size about 4.0 cm×4.0 cm was generated on the back of every rat. Group A, the sheep ADM microparticle and autoallergic skin microparticle were mixed according to the ratio of 5:1, coating on wound of rat back. Group B, the sheep ADM microparticle and autoallergic skin microparticle were mixed according to the ratio of 2:1. Group C, autoallergic skin microparticle was only put on wound and be covered with heterograft. We observed the development of wound healing and compared the wound contraction rate among the three groups.â© Results: Three groups displayed same speed on extending of autoallergic skin microparticle and wound healing. The skin microparticles in Group A were wrapped up by around tissues and fused each other. A few renewal blood vessels were found in tissues, and ADM was replaced by around tissues and mixed with autoallergic skin microparticle. At the muscle surface, a few derma tissues distributed into point or patch, and the wound contraction rate was the lowest one among the 3 groups. The skin microparticles in Group B were mixed with more sheep ADMs than those in Group A. Some ADMs were wrapped by around tissues but could not been absorbed. Sheep ADM microparticles were free from around tissues, and the wound healing was delayed. The wound contraction rate in Group B was higher than that in Group A. The wound healing in Group C was faster than that in Group B, but there were few derma tissues under the skin. The wound contraction rate was the highest one.â© Conclusion: Mixing sheep ADM microparticle with autoallergic skin microparticle according to the ratio of 5:1 is good for regenerating derma tissues, and it can improve healing effect of wound.