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INTRODUCTION: Inflammation and oxidative stress play significant roles in the development of chronic kidney disease (CKD). Given the recognized antioxidant properties of vitamin C, our study aimed to explore the correlation between CKD and serum vitamin C levels. METHODS: Data were gathered from the 2017-2018 National Health and Nutrition Examination Survey. Participants below 18 years of age, pregnant individuals, those lacking essential data for CKD diagnosis, or individuals with incomplete serum vitamin C data were excluded. Subgroup and weighted multivariable logistic regression analyses were performed to assess the potential correlation between serum vitamin C and CKD. RESULTS: Our study comprised 4969 participants, revealing an overall CKD prevalence of 15.0%. The results indicated that individuals with reduced serum vitamin C levels were more likely to be male, possess lower educational attainment, have a diminished poverty-income ratio, engage in heavy drinking, and be current smokers. Additionally, they exhibited a higher prevalence of obesity and diabetes. Significantly, participants in the third quartile group experienced a 37.0%, 47.0%, and 46.6% decrease in the risk of developing albuminuria, low estimated glomerular filtration rate (eGFR), and CKD, respectively. Subgroup analysis demonstrated that individuals between 65 and 80 years of age showed a statistically reduced risk of developing CKD and low eGFR when their serum vitamin C levels fell in the third and fourth quartile groups. CONCLUSIONS: Our findings reveal a correlation between elevated serum vitamin C levels and a decreased risk of developing albuminuria, low eGFR, and CKD. Appropriately increasing serum vitamin C levels may hold promise in protecting renal function, particularly among older individuals.
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Albuminuria , Insuficiencia Renal Crónica , Adulto , Femenino , Embarazo , Humanos , Masculino , Encuestas Nutricionales , Antioxidantes , Ácido Ascórbico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
BACKGROUND: This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD). METHODS: We comprehensively searched 5 databases for randomized controlled trials (RCTs) investigating roxadustat for anemia in DD-CKD patients. RevMan 5.0 was used to extract and synthesize data for meta-analysis. RESULTS: Ten different RCTs (9 studies) and 5698 DD-CKD patients with anemia were included. Our findings revealed that when compared to the erythropoiesis-stimulating agents (ESAs) group, the roxadustat group showed increased hemoglobin levels [MD (Mean Difference) 0.25 g/dL (95%CI 0.14 g/dL to 0.36 g/dL), p < 0.00001] and improved iron-utilization by increasing serum iron [MD 1.85 µmol/L], total iron binding capacity [MD 35.73 µg/dL], transferrin saturation [MD 1.19%], and transferrin level [MD 0.40 g/L]. In addition, we found that roxadustat significantly decreased the low-density lipoprotein-cholesterol [MD -0.39 mmol/L] and total cholesterol [MD -0.6 mmol/L]. In patients with a C-reactive protein level that exceeds the upper limit of the normal range, hemoglobin levels were higher for roxadustat than for ESAs [MD 0.39 g/dL]. Treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events were not significantly different between the two groups. CONCLUSIONS: The hemoglobin levels of DD-CKD patients were significantly increased and not affected by the inflammatory state after roxadustat treatment. Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs.
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Anemia , Enfermedades Cardiovasculares , Hematínicos , Humanos , Diálisis Renal , Hierro , LDL-Colesterol , Glicina , Transferrinas , HemoglobinasRESUMEN
Multi-hop networks have become popular network topologies in various emerging Internet of Things (IoT) applications. Batched network coding (BNC) is a solution to reliable communications in such networks with packet loss. By grouping packets into small batches and restricting recoding to the packets belonging to the same batch; BNC has much smaller computational and storage requirements at intermediate nodes compared with direct application of random linear network coding. In this paper, we discuss a practical recoding scheme called blockwise adaptive recoding (BAR) which learns the latest channel knowledge from short observations so that BAR can adapt to fluctuations in channel conditions. Due to the low computational power of remote IoT devices, we focus on investigating practical concerns such as how to implement efficient BAR algorithms. We also design and investigate feedback schemes for BAR under imperfect feedback systems. Our numerical evaluations show that BAR has significant throughput gain for small batch sizes compared with existing baseline recoding schemes. More importantly, this gain is insensitive to inaccurate channel knowledge. This encouraging result suggests that BAR is suitable to be used in practice as the exact channel model and its parameters could be unknown and subject to changes from time to time.
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The development of chemo/photothermal nanotherapeutic systems with excellent photothermal performance, stable drug loading, tumor targeting and strong membrane penetration still remains a challenge. To address this problem, herein a rod-like nanocomposite system (AuNR@FA-PR/PEG) forming from folic acid (FA) terminated carboxylated cyclodextrin (CD) pseudopolyrotaxane (FA-PR) and polyethylene glycol (PEG) modifying gold nanorods (AuNR) was reported. Cisplatin (CDDP) was loaded in AuNR@FA-PR/PEG via coordination bonds to prepare a rod-like pH-responsive nanosystem (AuNR@FA-PR/PEG/CDDP) with chemotherapy/photothermal therapy. The rod-like morphology of AuNR@FA-PR/PEG was characterized by transmission electron microscope. In vitro drug release experiments showed the pH-responsive of AuNR@FA-PR/PEG/CDDP. In vivo real-time imaging assays proved AuNR@FA-PR/PEG/CDDP could rapidly enrich in the tumor area and stay for a long time because of folate targeting and their rod-like morphology. In vivo photothermal imaging assays showed AuNR@FA-PR/PEG/CDDP excellent photothermal performance, the average temperature of tumor region could reach 63.5 °C after 10 min irradiation. In vitro and in vivo experiments also demonstrated that the combined therapy of chemotherapy and photothermal therapy had an outstandingly synergistic effect and improved the therapeutic efficacy comparing with chemotherapy and photothermal therapy alone. Therefore, the prepared rod-like AuNR@FA-PR/PEG/CDDP will provide a new strategy for the effective treatment of cancer.
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Hipertermia Inducida , Nanocompuestos , Neoplasias , Línea Celular Tumoral , Cisplatino/farmacología , Doxorrubicina/química , Ácido Fólico/química , Humanos , Concentración de Iones de Hidrógeno , Nanocompuestos/uso terapéutico , Neoplasias/tratamiento farmacológico , Fototerapia/métodos , Terapia Fototérmica , Polietilenglicoles/químicaRESUMEN
The development of cost-effective, portable, and ease-of-use sensing system for on-site genetic diagnostics is highly desirable for pathogen screening and infectious disease diagnosis. This study develops (1) a paper-based biochip which is able to integrate the loop-mediated isothermal amplification (LAMP) protocols for simultaneous detection of Escherichia coli O157:H7, Salmonella spp., and Staphylococcus aureus, and (2) a stand-alone smartphone-based portable device which can control exactly 65 °C for isothermal amplification as well as collect and analyze the thus generated fluorescence signals. The reported sensing system has been successfully demonstrated for foodborne pathogen detection with a limit of detection of 2.8 × 10-5 ng µL-1. Spiked milk samples with concentration as low as 10 CFU mL-1 were successfully determined within 4 h, demonstrating the practicality of the reported sensing system in the fields. The reported sensing system featuring simplicity and reliability is ideally suited for genetic diagnostics in low resource settings.
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Escherichia coli O157 , Teléfono Inteligente , Escherichia coli O157/genética , Reproducibilidad de los Resultados , Staphylococcus aureus/genéticaRESUMEN
With the rapid expansion of graphs and networks and the growing magnitude of data from all areas of science, effective treatment and compression schemes of context-dependent data is extremely desirable. A particularly interesting direction is to compress the data while keeping the "structural information" only and ignoring the concrete labelings. Under this direction, Choi and Szpankowski introduced the structures (unlabeled graphs) which allowed them to compute the structural entropy of the Erdos-Rényi random graph model. Moreover, they also provided an asymptotically optimal compression algorithm that (asymptotically) achieves this entropy limit and runs in expectation in linear time. In this paper, we consider the stochastic block models with an arbitrary number of parts. Indeed, we define a partitioned structural entropy for stochastic block models, which generalizes the structural entropy for unlabeled graphs and encodes the partition information as well. We then compute the partitioned structural entropy of the stochastic block models, and provide a compression scheme that asymptotically achieves this entropy limit.
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Heavy metal pollution in surface water is a global environmental problem. This study analyzed the trends, health risks, and sources of eight dissolved heavy metal species in river and lake water across five continents (Africa, Asia, Europe, North America, and South America; Oceania was excluded owing to a lack of data) for the period 1970-2017. We wanted to assess the effects of various implemented countermeasures to pollution and to determine those that could be adopted worldwide. Collectively, the water system showed increasing trends for Cd, Cr, Cu, Ni, Mn, and Fe and decreasing trends for Pb and Zn. The mean dissolved concentrations of most heavy metals were highest in Asia and lowest in Europe. Most heavy metals had low non-carcinogenic risks over this period. The cancer risks associated with Pb were lower than the hazardous level on all five continents over the five decades, whereas the cancer risks related to Cr exceeded the hazardous level in the 1970s, 2000s, and 2010s, and in Africa, Asia, and North America over the entire period. Mining and manufacturing were consistently found to be critical sources of metal pollution from 1970 to 2017. However, the heavy metal sources differed significantly by continent, with waste discharge and rock weathering dominant in Africa; mining and manufacturing, along with rock weathering, are dominant in Asia and South America; fertilizer and pesticide use, along with rock weathering, are dominant in North America; and mining and manufacturing, waste discharge, and rock weathering are dominant in Europe. Global trends in the metal loadings in water and in relevant pollution-control measures suggest that countermeasures in Europe have successfully controlled heavy metal pollution. The successful measures include implementing rigorous standards for metal emissions, limiting the metal concentrations in products, and rigorously treating metal-contaminated waste. Therefore, the measures implemented in Europe should be extended worldwide to treat heavy metal pollution in water.
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Exposición a Riesgos Ambientales/análisis , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Contaminación Química del Agua/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente , Humanos , Lagos , RíosRESUMEN
Bioaccumulation of heavy metals in aquatic plants is significantly affected by hydrological regime and therefore the accumulation and translocation of cadmium in five organs-panicle, leaf, stem, root, and bud-of an emergent plant (Miscanthus sacchariflorus) were compared between the submerged environment and non-submerged environment. In the submerged condition, the cadmium concentration was higher in the panicle and leaf than in the stem, root, and bud. Cadmium concentration in the root exhibited a positive regression with cadmium concentration in the sediment. However, cadmium concentration in the panicle, leaf, stem, and bud exhibited no significant regression with cadmium concentration in the sediment. In the non-submerged environment, the cadmium concentration was higher in the below-ground organs than in the aboveground organs. The mean bioaccumulation coefficient in the 24 investigated plots in the submerged environment was higher than that in the 20 and 40 mg kg-1 cadmium treatments in the non-submerged environment. The mean translocation factor in the submerged environment was nine times higher than that in non-submerged environment. These results indicate that submergence enhanced cadmium bioaccumulation in the aboveground organs and that this plant can be used to remove heavy metals from polluted rivers and lakes.
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Metales Pesados , Contaminantes del Suelo , Biodegradación Ambiental , Cadmio , PoaceaeRESUMEN
The SARS-CoV-2 pandemic, now in its third year, has had a profound impact on public health and economics all over the world. Different populations showed varied susceptibility to this virus and mortality after infection. Clinical and laboratory data revealed that the uncontrolled inflammatory response plays an important role in their poor outcome. Herein, we summarized the role of NF-κB activation during SARS-CoV-2 invasion and replication, particularly the angiotensin-converting enzyme 2 (ACE2)-mediated NF-κB activation. Then we summarized the COVID-19 drugs' impact on NF-κB activation and their problems. A favorable prognosis is linked with timely treatment with NF-κB activation inhibitors, such as TNFα, IL-1ß, and IL-6 monoclonal antibodies. However, further clinical researches are still required to clarify the time window, dosage of administration, contraindication, and potential side effects of these drugs, particularly for COVID-19 patients with hypertension, hyperglycemia, diabetes, or other chronic diseases.
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COVID-19 , Humanos , FN-kappa B/metabolismo , Peptidil-Dipeptidasa A/metabolismo , SARS-CoV-2 , Transducción de SeñalRESUMEN
Fast co-pyrolysis offers a sustainable solution for upcycling polymer waste, including scrap tyre and plastics. Previous studies primarily focused on slow heating rates, neglecting synergistic mechanisms and sulphur transformation in co-pyrolysis with tyre. This research explored fast co-pyrolysis of scrap tyre with polypropylene (PP), low-density polyethylene (LDPE), and polystyrene (PS) to understand synergistic effects and sulphur transformation mechanisms. A pronounced synergy was observed between scrap tyre and plastics, with the nature of the synergy being plastic-type dependent. Remarkably, blending 75 wt% PS or LDPE with tyre effectively eliminated sulphur-bearing compounds in the liquid product. This reduction in sulphur content can substantially mitigate the release of hazardous materials into the environment, emphasizing the environmental significance of co-pyrolysis. The synergy between PP or LDPE and tyre amplified the production of lighter hydrocarbons, while PS's interaction led to the creation of monocyclic aromatics. These findings offer insights into the intricate chemistry of scrap tyre and plastic interactions and highlight the potential of co-pyrolysis in waste management. By converting potential pollutants into valuable products, this method can significantly reduce the release of hazardous materials into the environment.
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Calor , Polietileno , Polietileno/química , Pirólisis , Polipropilenos , Poliestirenos , Azufre , Sustancias Peligrosas , Plásticos/químicaRESUMEN
Furfural (C5H4O2) is an important platform chemical for the synthesis of next-generation bio-fuels. Herein, we report a novel and reusable heterogeneous catalyst, Pd-PdO/ZnSO4 with 1.1 mol% palladium (Pd), for the production of furfural by flash pyrolysis of lignocelluloses at 400 °C. For both dry and wet C6 cellulose and its monomers, the furfural yields reach 74-82 mol%, relative to 96 mol% from C5 xylan and 23-33 wt% from sugarcane bagasse and corncob. The catalyst has a well-defined structure and bifunctional property, comprising a ZnSO4 support for the dehydration and isomerization of glucose, and a local core-shell configuration for metallic Pd0 encapsulated by an oxide (PdO) layer. The PdO layer is active for the Grob fragmentation of formaldehyde (HCHO) from glucose, which is subsequently in-situ steam reformed into syn-gas (i.e. H2 and CO), whereas the Pd0 core is active in promoting the last dehydration step for the formation of furfural.
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BACKGROUND: Most cancer patients are accompanied by anemia, which will be more serious when combined with end-stage renal disease (ESRD). At present, cancer-related anemia and renal anemia treatments mainly include erythropoiesis-stimulating agents (ESAs), iron supplementation, and blood transfusion, but their effects are often poor with several safety concerns. We have used roxadustat to treat anemia in a cancer patient with ESRD and achieved a successful outcome for the first time. CASE SUMMARY: A 64-year-old man was diagnosed with right renal cancer (clear cell renal cell carcinoma). He did not receive surgery or radiotherapy before admission. He was treated with oral soltan (sunitinib malate) on April 18, 2017. During oral chemotherapy, he had numerous complications, including anemia, hypertension, thyroid hypofunction, skin pigment loss, and renal function deterioration. At last, he progressed to ESRD and began hemodialysis treatment. We initially treated the patient with high-dose ESAs, iron supplementation, adequate dialysis, and even blood transfusion, but his anemia did not improve. Roxadustat is a newly developed drug for renal anemia treatment, but not for cancer-related anemia, let alone to treat anemia in cancer patients with ESRD. We prescribed oral roxadustat to the patient. After a period, his hemoglobin gradually increased. He did not have obvious discomfort symptoms, and his tumor did not progress significantly. CONCLUSION: Oral roxadustat could achieve good results in treating anemia in cancer patients with ESRD.
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The distribution range of plants is usually related to their competitiveness. The competitive ability between common widespread, which are generally considered to be invasive, and common endemic species, is still not very clear. Five plant communities were monitored in the field to compare the competitive abilities of widespread species, Phragmites australis, and endemic species, Triarrhena lutarioriparia, in the Dongting Lake wetlands. The ratios of individual numbers of T. lutarioriparia to P. australis per square meter were found to be 9:0, 14:1, 10:5, 7:6, and 0:11 in the five respective communities. A manipulation experiment was then performed with five planting modes (T. lutarioriparia: P. australis was 4:0, 3:1, 2:2, 1:3, and 0:4, respectively). Results from field monitoring showed that the two plant species exhibited similar decreased survival percentages during flooding. P. australis had higher aboveground biomass before the flooding and a higher relative elongation rate, whereas T. lutarioriparia had higher aboveground biomass after flooding and a higher relative growth rate (RGR). P. australis had a higher competitive ability than T. lutarioriparia before and after the flooding. The manipulation experiment revealed that P. australis had a higher survival percentage than T. lutarioriparia, with no differences in plant biomass, RGR, and the relative elongation rate between the two species. P. australis was found to have a higher competitive ability than T. lutarioriparia in the early growing stage and a lower competitive ability in the middle and later stages. The relative yield total in the field monitoring and manipulation experiment was 1, indicating that T. lutarioriparia and P. australis occupied different niches in the experimental conditions. It was concluded that, compared with T. lutarioriparia, P. australis has a higher competitive ability in submerged habitats and a lower competitive ability in the non-submerged habitat. The niche differences between the two species enabled their coexistence in the Dongting Lake wetlands with seasonal flooding.
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Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic-based methods require complex infrastructure and expensive equipment, which are not suitable for low-resource settings. Over the past years, smartphone-based point-of-care testing (POCT) has rapidly emerged as a potential alternative to laboratory-based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory-based and POCT-based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone-based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone-based POCT diagnostics for various viruses including COVID-19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone-based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease-causing viruses worldwide.
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COVID-19 , Infección por el Virus Zika , Virus Zika , COVID-19/diagnóstico , Técnicas de Laboratorio Clínico , Humanos , Laboratorios , Pruebas en el Punto de Atención , Teléfono Inteligente , Infección por el Virus Zika/diagnósticoRESUMEN
Tumor necrosis factor α (TNFα)- and interleukin 1ß (IL-1ß)-induced nuclear factor-κB (NF-κB) activation play key roles in inflammation, immunity, and cancer development. Here, we identified one of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 15 (USP15), as a positive regulator in both TNFα- and IL-1ß-induced NF-κB activation. Overexpression of USP15 potentiated TNFα- or IL-1ß-triggered NF-κB activation and downstream gene transcription, whereas knockdown of USP15 had opposite effects. Mechanistically, upon TNFα stimulation, USP15 showed an enhanced interaction with transforming growth factor-ß activated kinase-1 (TAK1)-TAK1 binding protein (TAB) complex to inhibit the proteolysis of TAB2/3 by different pathways. Apart from deubiquitination dependently inducing cleavage of lysine 48-linked TAB2 ubiquitination, USP15 also DUB independently inhibited lysosome-associated TAB2 degradation, thus enhanced TAB2 stabilization. For TAB3, USP15 inhibited NBR1-mediated selective autophagic TAB3 degradation independent of its deubiquitinating activity. Together, our results reveal a novel USP15-mediated mechanism through which efficient NF-κB activation is achieved by differentially maintaining the TAB2/3 stability.
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Proteínas Adaptadoras Transductoras de Señales/química , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Autofagia , Células HEK293 , Células HeLa , Humanos , FN-kappa B/genética , Proteolisis , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Proteasas Ubiquitina-Específicas/genética , UbiquitinaciónRESUMEN
A kind of specific cyclodextrin polyrotaxanes (PRs) drug delivery system was developed for an effective drug delivery and enhancing antitumor effect. In this work, we prepared the PR by using α-CD derivatives and dicarboxyl-PEG (Mn = 4200) self-assembling and end-capping with ß-CD derivatives. Then, we chose d-a-Tocopheryl polyethylene glycol 1000 succinate (TPGS) with an antitumor effect to modify the PR. The modified PRs have a certain anticancer effect and can assist the anticancer drug to treat cancer. The 10-hydroxycamptothecin (HCPT) was combined to the specific PRs by covalent bonds to prepare drug-loaded specificity PRs (PR-TPGS-HCPT). The enhanced antitumor activities of PR-TPGS-HCPT were studied by in vitro and in vivo experiments, and the experiment results proved that the TPGS could effectively assist the drug to treat cancer and prolong the lifetime of the tumor-bearing mice. Therefore, this research provides a promising drug-loaded material for the cancer treatment and the specific water-soluble PRs will have potential applications in the biomedical field.
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Anticarcinógenos/farmacología , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Rotaxanos/farmacología , Animales , Anticarcinógenos/química , Camptotecina/análogos & derivados , Camptotecina/química , Camptotecina/farmacología , Línea Celular Tumoral , Celulosa/química , Celulosa/farmacología , Ciclodextrinas/química , Ciclodextrinas/farmacología , Humanos , Ratones , Nanopartículas/química , Neoplasias/patología , Rotaxanos/química , Vitamina E/química , Vitamina E/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: Sodium-glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. MATERIALS & METHODS: In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure-activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking. HQSAR and topomer CoMFA were used to construct models. Molecular docking was conducted to investigate the interaction of triazole derivatives and homology modeling of SGLT2, as well as to validate the results of the HQSAR and topomer CoMFA models. RESULTS: The most effective HQSAR and topomer CoMFA models exhibited noncross-validated correlation coefficients of 0.928 and 0.891 for the training set, respectively. External predictions were made successfully on a test set and then compared with previously reported models. The graphical results of HQSAR and topomer CoMFA were proven to be consistent with the binding mode of the inhibitors and SGLT2 from molecular docking. CONCLUSION: The models and docking provided important insights into the design of potent inhibitors for SGLT2.
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Relación Estructura-Actividad Cuantitativa , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Triazoles/farmacología , Humanos , Modelos Moleculares , Transportador 2 de Sodio-Glucosa , Triazoles/síntesis química , Triazoles/químicaRESUMEN
Excessive nuclear factor-κB (NF-κB) activation mediated by tumor necrosis factor α (TNFα) plays a critical role in inflammation. Here we demonstrate that angiopoietin-like 8 (ANGPTL8) functions as a negative feedback regulator in TNFα-triggered NF-κB activation intracellularly. Inflammatory stimuli induce ANGPTL8 expression, and knockdown or knockout of ANGPTL8 potentiates TNFα-induced NF-κB activation in vitro. Mechanistically, upon TNFα stimulation, ANGPTL8 facilitates the interaction of IKKγ with p62 via forming a complex, thus promoting the selective autophagic degradation of IKKγ. Furthermore, the N-terminal domain mediated self-oligomerization of ANGPTL8 is essential for IKKγ degradation and NF-κB activation. In vivo, circulating ANGPTL8 level is high in patients diagnosed with infectious diseases, and the ANGPTL8/p62-IKKγ axis is responsive to inflammatory stimuli in the liver of LPS-injected mice. Altogether, our study suggests the ANGPTL8/p62-IKKγ axis as a negative feedback loop that regulates NF-κB activation, and extends the role of selective autophagy in fine-tuned inflammatory responses.
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Proteínas Similares a la Angiopoyetina/metabolismo , Autofagia , Quinasa I-kappa B/metabolismo , FN-kappa B/metabolismo , Hormonas Peptídicas/metabolismo , Células A549 , Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/sangre , Proteínas Similares a la Angiopoyetina/genética , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Células Hep G2 , Humanos , Quinasa I-kappa B/genética , Inflamación/sangre , Inflamación/genética , Inflamación/metabolismo , Interleucina-1beta/farmacología , Masculino , Ratones Endogámicos C57BL , FN-kappa B/genética , Hormonas Peptídicas/sangre , Hormonas Peptídicas/genética , Proteína Sequestosoma-1/genética , Proteína Sequestosoma-1/metabolismoRESUMEN
Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.