RESUMO
Reactive oxygen species (ROS) encompass a collection of intricately linked chemical entities characterized by individually distinct physicochemical properties and biological reactivities. Although excessive ROS generation is well known to underpin disease development, it has become increasingly evident that ROS also play central roles in redox regulation and normal physiology. A major challenge in uncovering the relevant biological mechanisms and deconvoluting the apparently paradoxical roles of distinct ROS in human health and disease lies in the selective and sensitive detection of these transient species in the complex biological milieu. Small-molecule-based fluorescent sensors enable molecular imaging of ROS with great spatial and temporal resolution and have thus been appreciated as excellent tools for aiding discoveries in modern redox biology. We review a selection of state-of-the-art sensors with demonstrated utility in biological systems. By providing a systematic overview based on underlying chemical sensing mechanisms, we wish to highlight the strengths and weaknesses in prior sensor works and propose some guiding principles for the development of future probes.
Assuntos
Técnicas Biossensoriais/métodos , Espécies Reativas de Oxigênio/análise , Corantes Fluorescentes , Imagem Óptica , Oxirredução , Estresse OxidativoRESUMO
RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other RNA systems, such as siRNA and CRISPR technologies, the ribozyme tools are still far from broad applications on RNAi due to their poor performance in the cellular context. In this work, we report an efficient RNAi tool based on chemically modified hammerhead ribozyme (HHR). By the introduction of an intramolecular linkage into the minimal HHR to reconstruct the distal interaction within the tertiary ribozyme structure, this cross-linked HHR exhibits efficient RNA substrate cleavage activities with almost no sequence constraint. Cellular experiments suggest that both exogenous and endogenous RNA expression can be dramatically knocked down by this HHR tool with levels comparable to those of siRNA. Unlike the widely applied protein-recruiting RNA systems (siRNA and CRISPR), this ribozyme tool functions solely on RNA itself with great simplicity, which may provide a new approach for gene manipulation in both fundamental and translational studies.
Assuntos
RNA Catalítico , RNA Catalítico/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Processamento de Proteína Pós-Traducional , Conformação de Ácido NucleicoRESUMO
Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti-inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film-forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re-epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/ß-catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/ß-catenin signalling pathway may provide new ideas to guide the design of biomaterial-based wound dressings for chronic wound repair.
Assuntos
Berberina , Modelos Animais de Doenças , Úlcera por Pressão , Ratos Sprague-Dawley , Via de Sinalização Wnt , Cicatrização , Animais , Úlcera por Pressão/tratamento farmacológico , Berberina/farmacologia , Berberina/uso terapêutico , Ratos , Cicatrização/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Masculino , Polímeros/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Patients in the intensive care unit (ICU) are highly susceptible to malnutrition, and while enteral nutrition via nasogastric tube is the preferred method, there is a risk of inadvertent reflux and aspiration. Therefore, clinicians have turned to nasointestinal tubes (NET) for enteral nutrition as an alternative option. But the precise localization of NET presents an ongoing challenge. We proposed an innovative approach to provide a valuable reference for clinicians involved in NET placement. METHOD: Data were obtained retrospectively from the medical records of adult patients with a high risk of aspiration or gastric feeding intolerance who had a NET placed in the ICU of Zhejiang Provincial People's Hospital between October 1, 2017, and October 1, 2023. The collected data were subjected to statistical analysis using SPSS and R software. RESULT: There were 494 patients who met the inclusion and exclusion criteria. The first-pass success rate was 81.4% (n = 402). The success of a patient's initial NET placement was found to be associated with Angle SPC and Distance CP, as determined by univariate analysis (25.6 ± 16.7° vs. 41.9 ± 18.0°, P < 0.001; 40.0 ± 26.2 mm vs. 62.0 ± 31.8 mm, P < 0.001, respectively). By conducting a multivariate regression analysis, we identified a significant association between pyloric types and the success rate of placing NET (OR 29.559, 95%CI 14.084-62.038, P < 0.001). CONCLUSION: Angle SPC, Distance CP, and the type of pylorus are independently associated with successful initial placement of NET. Besides, patients with the outside type of pylorus (OP-type) exhibit a higher rate of initial placement success.
Assuntos
Nutrição Enteral , Intubação Gastrointestinal , Humanos , Estudos Retrospectivos , Feminino , Masculino , Intubação Gastrointestinal/métodos , Nutrição Enteral/métodos , Pessoa de Meia-Idade , Idoso , Análise Multivariada , Estômago/diagnóstico por imagem , Adulto , Unidades de Terapia IntensivaRESUMO
Objective: This study aims to investigate the use of an elastic traction band in conjunction with pain evaluation in geriatric patients after hip replacement. Methods: Eighty hip arthroplasty cases involving senior patients at our institution were chosen for this study, covering the period from February 2021 to January 2022. They were separated into the control and observation groups using the premise of comparing and contrasting the two groups' shared fundamental characteristics. Traditional nursing care was given to the control group, while the observation group got an elastic stretch traction belt and pain assessment nursing care. The application effect of the two groups was observed. Results: Before surgery, there was no statistically significant difference in the Harris hip function score between the two groups (P > .05). Harris scores for research items in both groups improved 6 months after surgery, compared to scores obtained before surgery (P < .05), and the increase was greater in the observation group than in the control group (P < .05). Self-efficacy for physical activity, coping, and the overall SER scale were all greater in the observation group than in the control group (P < .05). There was no statistically significant difference between the two groups on any measure of material wellbeing (P > .05). Mental and physical health scores were better in the observation group than in the control group (P < .05). Patients' social dimensions were compared to those of two control groups, and the results showed no statistically significant difference in terms of social function aspects (P > .05), although the control group reported much lower levels of enjoyment, learning, and work, the observation group reported significantly greater levels (P < .05). Patient treatment compliance study using a rank sum test revealed that the observation group's postoperative exercise compliance was considerably greater than that of the control group. Observation group members were more compliant than control group members, with an average rank of 30.829 compared to 40.171 for both groups (P < .05). Conclusion: Patients who have had hip arthroplasty may benefit from using an elastic traction belt in conjunction with pain assessment to increase the likelihood that they would participate in rehabilitation exercises, so enhancing their self-efficacy, hip function, and quality of life.
Assuntos
Artroplastia de Quadril , Humanos , Idoso , Artroplastia de Quadril/métodos , Medição da Dor , Tração , Qualidade de VidaRESUMO
The abnormal immune response mediated by malignant melanoma is related to PD1. Paeonol has pharmacological antitumor activity. Previous studies have indicated that paeonol induces tumor cell apoptosis, but its underlying mechanism in tumor immunity remains unknown. In this study, malignant melanoma was established in normal and thymectomized mice to determine the important role of the thymus in the antitumor effects of paeonol. Paeonol-treated thymocytes were cocultured with melanoma cell spheres to further evaluate the regulatory role of thymocytes in tumor immune dysfunction. Studies have shown that PD1 may be targeted by miR-139-5p. Our results revealed that tumor-induced thymic atrophy was significantly accompanied by high PD1 expression and low miR-139-5p expression. Interestingly, paeonol significantly reversed thymic atrophy and largely protected thymocytes against low PD1 expression and high miR-139-5p expression. Dual-luciferase assays indicated that miR-139-5p interacted with the 3' untranslated region (3'-UTR) of PD1. These results showed that paeonol alleviates PD1-mediated antitumor immunity by reducing miR-139-5p expression and demonstrated a novel mechanism for melanoma immunotherapy.
Assuntos
Melanoma , MicroRNAs , Animais , Camundongos , Regulação para Cima , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Apoptose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Melanoma Maligno CutâneoRESUMO
OBJECTIVE: This study aims to investigate the feasibility of the anterior transpedicular root screw (ATPRS) intervertebral fusion system for the cervical spine and provide a basis for the design of the ATPRS intervertebral fusion system. METHODS: A total of 60 healthy adult cervical spine CT images examined from our hospital were selected, including 30 males and 30 females, with an average age of 39.6 ± 4.8 years. The image data was imported into Mimics 21.0 software in DICOM format for 3D model reconstruction. Simulated screw insertion was performed on both sides of the midline of the intervertebral space. The entry point (P1) was determined when the upper and lower screw paths did not overlap. When the screw was tangent to the medial edge of the Luschka joint, the insertion point was determined as the entry point (P2). Measurements were taken and recorded for the following parameters: distance from the screw entry point to the midline of the intervertebral space (DPM), the simulated screw length, inclination angle, cranial/caudal tilted angle, the anterior-posterior (AP) and mediolateral (ML) diameters of the cervical intervertebral space, the heights of the anterior, middle, and posterior edges of the cervical intervertebral space, and the curvature diameter of the lower end plate of the cervical vertebral body. Statistical analysis was performed on the measurement results. RESULTS: The screw entry area (P1P2) showed an increasing trend from C3-C7 in both male (2.92-6.08 mm) and female (2.32-5.12 mm) groups. There were statistical differences between men and women at the same level (P < 0.05). The average screw length of men and women was greater than 20 mm, and the upper and lower screw lengths showed an increasing trend from C3 to C7. In the area where screws could be inserted, the range of screw inclination was as follows: male group upper screw (47.73-66.76°), lower screw (48.05-65.35°); female group upper screw (49.15-65.66°) and lower screw (49.42-63.29°); The range of cranial/caudal tilted angle of the screw was as follows: male group upper screw (32.06-39.56°), lower screw (29.12-36.95°); female group upper screw (30.97-38.92°) and lower screw (27.29-37.20°). The anterior-posterior diameter and mediolateral diameter of the cervical intervertebral space showed an increasing trend from C3 to C7 in both male and female groups. The middle height (MH) of the cervical intervertebral space was greater than the anterior edge height (AH) and posterior edge height (PD), with statistical differences (P < 0.05). CONCLUSIONS: Through the study of CT images of the cervical spine, it was determined that the ATPRS intervertebral fusion system has a feasible area for screw insertion in the cervical intervertebral space.
Assuntos
Parafusos Ósseos , Fusão Vertebral , Adulto , Humanos , Masculino , Feminino , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Tomografia Computadorizada por Raios X/métodos , Pescoço , Software , Fusão Vertebral/métodosRESUMO
Inflammation is a biological process that exists in a large number of diseases. If the magnitude or duration of inflammation becomes uncontrolled, inflammation may cause pathological damage to the host. HMGB1 and NF-κB have been shown to play pivotal roles in inflammation-related diseases. New drugs aimed at inhibiting HMGB1 expression have become a key research focus. In the present study, we showed that paeonol (Pae), the main active component of Paeonia suffruticosa, decreases the expression of inflammatory cytokines and inhibits the translocation of HMGB1 induced by lipopolysaccharide (LPS). By constructing HMGB1-overexpressing (HMGB1+ ) and HMGB1-mutant (HMGB1m ) RAW264.7 cells, we found that the nuclear HMGB1 could induce an LPS-tolerant state in RAW264.7 cells and that paeonol had no influence on the expression of inflammatory cytokines in HMGB1m RAW264.7 cells. In addition, the anti-inflammatory property of paeonol was lost in HMGB1 conditional knockout mice, indicating that HMGB1 is a target of paeonol and a mediator through which paeonol exerts its anti-inflammatory function. Additionally, we also found that HMGB1 and P50 competitively bound with P65, thus inactivating the NF-κB pathway. Our research confirmed the anti-inflammation property of paeonol and suggests that inhibiting the translocation of HMGB1 could be a new strategy for treating inflammation.
Assuntos
Acetofenonas/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Proteína HMGB1/metabolismo , Acetofenonas/química , Animais , Anti-Inflamatórios/química , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Proteína HMGB1/química , Proteína HMGB1/genética , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Knockout , Modelos Moleculares , NF-kappa B/metabolismo , Transporte Proteico , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Phagocytosis is a basic immune response to the invasion of pathogens. High mobility group protein B1 (HMGB1) is a DNA chaperone that is associated with phagocytosis. However, its influence on phagocytosis is debated. In the present study, HMGB1-mutant, HMGB1-overexpressing and HMGB1-silenced RAW264.7 cells were constructed. In addition, HMGB1 conditional knockout mice were constructed to determine the influence of HMGB1 on phagocytosis. Lipopolysaccharide (LPS) was used to stimulate the translocation of HMGB1 from the nucleus to the cytoplasm. Zymosan particles were used to test the phagocytic function of the macrophages. Our results showed that the accumulation of HMGB1 in the nucleus enhances the phagocytic function of the macrophages. By interacting with P53, nuclear HMGB1 may remain in the nucleus and decrease the negative influence of P53 on the phosphorylation of focal adhesion kinase (FAK). The increase in phosphorylated FAK promotes the formation of pseudopods and enhances the phagocytic ability of macrophages.
Assuntos
Proteína HMGB1/metabolismo , Macrófagos/metabolismo , Fagocitose/fisiologia , Transporte Proteico/fisiologia , Animais , Células Cultivadas , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fagocitose/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacosRESUMO
A closed-loop resonant fiber optic gyroscope (RFOG) configuration with three resonance frequency servo loops is proposed. By using one laser-servo loop and two symmetrical phase modulator (PM) servo loops, the effect of the reset due to the limited tracking range of the laser-servo loop is solved. Further long-term stability for 48 h and thermal stability at moderate rate measurements show that the output of the triple closed-loop RFOG is insensitive to environmental temperature variations. When the temperature increased from 17.5°C to 40.7°C in 1800 s and the maximum temperature rate was about 0.025°C/s during heating, the laser-servo loop was reset a total of 413 times. However, the output of the triple closed-loop RFOG is not affected by those frequent resets in the laser-servo loop because the two PM-servo loops are free of glitch pulses under this new scheme. Compared to the traditional double closed-loop RFOG, the thermal bias stability of the triple closed-loop RFOG is improved by a factor of 15 times from 29.8°/h to 1.88°/h.
RESUMO
To cope with harsh environments, the Artemia shrimp produces gastrula embryos in diapause, a state of obligate dormancy, having cellular quiescence and suppressed metabolism. The mechanism behind these cellular events remains largely unknown. Here, we study the regulation of cell quiescence using diapause embryos of Artemia We found that Artemia DEK (Ar-DEK), a nuclear factor protein, was down-regulated in the quiescent cells of diapause embryos and enriched in the activated cells of post-diapause embryos. Knockdown of Ar-DEK induced the production of diapause embryos whereas the control Artemia released free-swimming nuaplii. Our results indicate that Ar-DEK correlated with the termination of cellular quiescence via the increase in euchromatin and decrease in heterochromatin. The phenomena of quiescence have many implications beyond shrimp ecology. In cancer cells, for example, knockdown of DEK also induced a short period of cellular quiescence and increased resistance to environmental stress in MCF-7 and MKN45 cancer cell lines. Analysis of RNA sequences in Artemia and in MCF-7 revealed that the Wnt and AURKA signaling pathways were all down-regulated and the p53 signaling pathway was up-regulated upon inhibition of DEK expression. Our results provide insight into the functions of Ar-DEK in the activation of cellular quiescence during diapause formation in Artemia.
Assuntos
Artemia/embriologia , Proteínas de Artrópodes/biossíntese , Diapausa/fisiologia , Embrião não Mamífero/enzimologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Receptores da Família Eph/biossíntese , Via de Sinalização Wnt/fisiologia , Animais , Artemia/genética , Proteínas de Artrópodes/genética , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Humanos , Células MCF-7 , Receptores da Família Eph/genéticaRESUMO
Selective and sensitive molecular probes for hydrogen peroxide (H2 O2 ), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H2 O2 . A lack of reliable tools for in vivo imaging has hampered the development of H2 O2 mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H2 O2 -CL-510 was developed as a highly selective and sensitive probe for detection of H2 O2 both in vitro and in vivo. A rapid 430-fold enhancement of chemiluminescence was triggered directly by H2 O2 without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia-reperfusion injury-induced H2 O2 fluxes were visualized in rat brains using H2 O2 -CL-510, providing a new chemical tool for real-time monitoring of H2 O2 dynamics in living animals.
Assuntos
Peróxido de Hidrogênio/metabolismo , Luminescência , Sondas Moleculares/metabolismo , Animais , Encéfalo/metabolismo , Humanos , Limite de Detecção , Sondas Moleculares/química , Ratos , Bibliotecas de Moléculas Pequenas/metabolismo , Células THP-1RESUMO
BACKGROUND: Hyperphosphatemia, hypocalcemia, and elevation of parathyroid hormone (PTH) are typical abnormalities of uremic patients with Secondary hyperparathyroidism (SHPT). However, metabolic imbalance associated with SHPT is not well understood. METHODS: A total of 15 SHPT patients with an intact parathyroid hormone (iPTH) level > 600 pg/mL were set as preoperative (PR) group, 15 age- and gender-matched controls who had undergone parathyroidectomy plus forearm transplantation because of hyperparathyroidism and achieved an iPTH level <150 pg/mL were set as postoperative (PO) group. Metabolite profiling of these 30 uremic patients and five healthy controls (HC) was performed using ultra performance liquid chromatography-mass spectrometry. RESULTS: Five differential metabolites, including allyl isothiocyanate, L-phenylalanine, D-Aspartic acid, indoleacetaldehyde, and D-galactose correlated with PTH were identified in this study. Taking them as a biomarker signature, PR group can be distinguished from HC group with an area under the curve (AUC) of 0.947 (95% CI, 0.76-1) and PO group with an AUC of 0.6 (95% CI, 0.38-0.807). CONCLUSIONS: The serum metabolome correlated with PTH is successfully demonstrated for a better understanding of the pathogenesis of SHPT.
Assuntos
Biomarcadores/sangue , Hiperparatireoidismo Secundário/sangue , Metabolômica/métodos , Hormônio Paratireóideo/sangue , Uremia/sangue , Adulto , Idoso , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Ácido D-Aspártico/sangue , Feminino , Galactose/sangue , Humanos , Indóis/sangue , Isotiocianatos/sangue , Masculino , Pessoa de Meia-Idade , Fenilalanina/sangueRESUMO
Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species of hydrothermal vent communities, which inside its gill chamber harbors ectosymbioses with taxonomic invariability while compositional flexibility. Several studies have revealed that the establishment of symbiosis can be initiated and selected by innate immunity-related pattern recognition receptors (PRRs), such as C-type lectins (CTLs). In this research, a CTL was identified in R. exoculata (termed RCTL), which showed high expression at both mRNA and protein levels in the scaphognathite, an organ where the ectosymbionts are attached outside its setae. Linear correlationships were observed between the relative quantities of two major symbionts and the expression of RCTL based on analyzing different shrimp individuals. The recombinant protein of RCTL could recognize and agglutinate the cultivable γ-proteobacterium of Escherichia coli in a Ca2+-dependent manner, obeying a dose-dependent and time-cumulative pattern. Unlike conventional crustacean CTLs, the involvement of RCTL could not affect the bacterial growth, which is a key issue for the successful establishment of symbiosis. These results implied that RCTL might play a critical role in symbiotic recognition and attachment to R. exoculata. It also provides insights to understand how R. exoculata adapted to such a chemosynthesis-based environment.
Assuntos
Decápodes/genética , Decápodes/imunologia , Imunidade Inata/genética , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Escherichia coli/fisiologia , Perfilação da Expressão Gênica , Lectinas Tipo C/química , Filogenia , Alinhamento de Sequência , SimbioseRESUMO
Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species among hydrothermal vent communities along the Mid-Atlantic Ridge. This shrimp can tolerate high concentrations of heavy metals such as iron, but the mechanisms used for detoxification and utilization of excess metals remain largely unknown. Ferritin is a major iron storage protein in most living organisms. The central heavy subunit of ferritin (H-ferritin) possesses ferroxidase activity and converts iron from Fe2+ to Fe3+, the non-toxic form used for storage. In the present study, the H-ferritin RexFrtH was identified in the hydrothermal vent shrimp R. exoculata, and found to be highly expressed in the gill, the main organ involved in bioaccumulation of metals, at both RNA and protein levels. Accumulation of RexFrtH decreased from efferent to afferent vessels, coinciding with the direction of water flow through the gills. Fe3+ was localized with RexFrtH, and in vitro iron-binding and ferroxidase assays using recombinant RexFrtH confirmed the high affinity for iron. Based on these results, we propose a model of iron metabolism in R. exoculata gills; ferrous iron from ambient hydrothermal water accumulates and is converted and stored in ferric form by RexFrtH as an iron reservoir when needed for metabolism, or excreted as an intermediate to prevent iron overload. The findings expand our understanding of the adaptation strategies used by shrimps inhabiting extreme hydrothermal vents to cope with extremely high heavy metal concentrations.
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Apoferritinas/metabolismo , Decápodes/metabolismo , Fontes Hidrotermais , Ferro/metabolismo , AnimaisRESUMO
PURPOSE: Form II clopidogrel bisulfate (Plavix) has been extensively used in patients with acute coronary syndrome. However, the efficacy of form I clopidogrel bisulfate (Talcom) was less investigated. The aim of this study was to investigate the efficacy and safety of Talcom compared with Plavix. METHOD: Two hundred and forty-eight patients were recruited after receiving percutaneous coronary intervention (PCI). Participants were randomly assigned to Talcom or Plavix group, and administered with Talcom or Plavix 75 mg od respectively in combination with aspirin 100 mg od for 12 months. Primary endpoints were set as levels of adenosine diphosphate-induced platelet aggregation (PLADP) on the 5th day and at 1 month after randomization. Patients were followed-up for 5 years. Bleeding events and major adverse cardiovascular events (MACE) including cardiac death, non-fatal myocardial infarction, ischemic stroke, target lesion revascularization (TLR), and cardiogenic re-admission were recorded. RESULTS: On the 5th day and at 1 month after randomization, the antiplatelet effect of Talcom was non-inferior to that of Plavix [PLADP (5th day): 30% (22%, 43%) vs. 33% (22%, 44%), p = 0.007; PLADP (1 month): 29% (19%, 43%) vs. 31% (22%, 43%), p = 0.005]. A total of 208 patients completed the follow-up, the incidences of MACE and bleeding were both comparable, and the MACE-free survival did not differ between the two groups. However, the expenditure was 32% lower for Talcom compared to Plavix during the treatment period. CONCLUSIONS: The antiplatelet effect of Talcom is non-inferior to Plavix, and the clinical efficacy and safety of Talcom and Plavix at 5 years were not significantly different in this study.
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Clopidogrel/administração & dosagem , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Stents , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Aspirina/administração & dosagem , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Hydrogen peroxide (H2 O2 ) has been recognized as one of the most significant ROS (reactive oxygen species) in human health and disease. Because of the intrinsic attributes of H2 O2 -such as its low reactivity under physiological pH-it is exceedingly challenging to develop small-molecule fluorescent probes with high selectivity and sensitivity for visualization of H2 O2 in an intricate biological milieu. To address this gap, a rationally designed tandem Payne/Dakin reaction is reported that is specific to molecular recognition of H2 O2 . New H2 O2 probes based on this unique chemical strategy can be easily synthesized by a general coupling reaction, and the practical applicability of those probes has been confirmed by the visualization of endogenously produced H2 O2 in living cells. In particular, starvation-induced H2 O2 production in mouse macrophages has been detected by the novel probe in both confocal imaging and flow cytometry. This tandem Payne/Dakin reaction provides a basis for developing more sophisticated molecular tools to interrogate H2 O2 functions in biological phenomena.
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Peróxido de Hidrogênio/análise , Macrófagos/metabolismo , Imagem Molecular , Animais , Peróxido de Hidrogênio/metabolismo , Macrófagos/química , Camundongos , Células RAW 264.7RESUMO
We propose a promising method to fabricate controllable anisotropic morphologies in which the slit-based spatial focusing of femtosecond laser is used to create an elliptical-shaped intensity distribution at focal plane, inducing elliptical-shaped morphology with micro/nano-dual-scale structures. Our study shows that 1) by increasing slit width, minor axis increases while major axis and axial ratio decrease; 2) with fixed slit width and laser fluence above the threshold, axial ratio is independent of irradiation pulse number; and 3) when polarization direction is changed from 0° to 90°, the axial ratio of anisotropic morphology declines. As a case study, large-area periodic anisotropic hierarchical structures are fabricated with the bidirectional anisotropic wetting.
RESUMO
The most widespread type of RNA editing, conversion of adenosine to inosine (AâI), is catalyzed by two members of the adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2. These enzymes edit transcripts for neurotransmitter receptors and ion channels during adaption to changes in the physical environment. In the primitive crustacean Artemia, when maternal adults are exposed to unfavorable conditions, they release diapause embryos to withstand harsh environments. The aim of the current study was therefore to elucidate the role of ADAR of Artemia diapause embryos in resistance to stress. Here, we identified Artemia ADAR (Ar-ADAR), which harbors a putative nuclear localization sequence (NLS) and two double-stranded RNA-binding motifs (dsRBMs) in the amino-terminal region and an adenosine deaminase (AD) domain in the carboxyl-terminal region. Western blot and immunofluorescence analysis revealed that Ar-ADAR is expressed abundantly in post-diapause embryos. Artemia (n = 200, three replicates) were tested under basal and stress conditions. We found that Ar-ADAR was significantly induced in response to the stresses of salinity and heat-shock. Furthermore, in vivo knockdown of Ar-ADAR (n = 100, three replicates) by RNA interference induced formation of pseudo-diapause embryos, which lack resistance to the stresses and exhibit high levels of apoptosis. These results indicate that Ar-ADAR contributes to resistance to stress in Artemia diapause embryos.
Assuntos
Adenosina Desaminase/genética , Artemia/genética , Edição de RNA/genética , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Animais , Apoptose/genética , Sequência de Bases , Biologia Computacional , Diapausa , Embrião não Mamífero , Técnicas de Silenciamento de Genes , Sinais de Localização Nuclear , Interferência de RNA , RNA de Cadeia Dupla/genéticaRESUMO
Superoxide anion radical (O2(â¢-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(â¢-) detecting strategy involving O2(â¢-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(â¢-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(â¢-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(â¢-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(â¢-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(â¢-) in health and disease.