ABSTRACT
Accurate delineation of Gross Tumor Volume (GTV) is crucial for radiotherapy. Deep learning-driven GTV segmentation technologies excel in rapidly and accurately delineating GTV, providing a basis for radiologists in formulating radiation plans. The existing 2D and 3D segmentation models of GTV based on deep learning are limited by the loss of spatial features and anisotropy respectively, and are both affected by the variability of tumor characteristics, blurred boundaries, and background interference. All these factors seriously affect the segmentation performance. To address the above issues, a Layer-Volume Parallel Attention (LVPA)-UNet model based on 2D-3D architecture has been proposed in this study, in which three strategies are introduced. Firstly, 2D and 3D workflows are introduced in the LVPA-UNet. They work in parallel and can guide each other. Both the fine features of each slice of 2D MRI and the 3D anatomical structure and spatial features of the tumor can be extracted by them. Secondly, parallel multi-branch depth-wise strip convolutions adapt the model to tumors of varying shapes and sizes within slices and volumetric spaces, and achieve refined processing of blurred boundaries. Lastly, a Layer-Channel Attention mechanism is proposed to adaptively adjust the weights of slices and channels according to their different tumor information, and then to highlight slices and channels with tumor. The experiments by LVPA-UNet on 1010 nasopharyngeal carcinoma (NPC) MRI datasets from three centers show a DSC of 0.7907, precision of 0.7929, recall of 0.8025, and HD95 of 1.8702 mm, outperforming eight typical models. Compared to the baseline model, it improves DSC by 2.14 %, precision by 2.96 %, and recall by 1.01 %, while reducing HD95 by 0.5434 mm. Consequently, while ensuring the efficiency of segmentation through deep learning, LVPA-UNet is able to provide superior GTV delineation results for radiotherapy and offer technical support for precision medicine.
ABSTRACT
The intrinsic low electrical properties have hindered the enhancement of thermoelectric performance for n-type PbTe over a long period of time, primarily due to the generation of intrinsic Pb vacancies and other defects. In this work, PbTe samples with nonstoichiometric excess Pb atoms were successfully prepared by a melting reaction followed by spark plasma sintering. First, the introduction of precisely controlled excess Pb atoms has effectively eliminated the typical p-n transition phenomenon in PbTe systems by suppressing the generation of Pb vacancies. Further, the vacuum annealing process employed in nonstoichiometric samples increases the carrier mobility significantly because of the improved crystallinity and the lowered holes. Thus, the Hall mobility was optimized from 754.3 to 1215.9 cm2 V-1 s-1, while the power factor was ultimately elevated from 3087.8 to 4565.7 µW m-1 K-2 for the Pb1.03Te sample at 323 K. Benefited from the enhanced electrical transport properties near room temperature, an average zT â¼ 1.03 ranging from 323 to 723 K was achieved, demonstrating an outstanding performance in n-type nondoped PbTe. This work provides guidance for optimizing the thermoelectric performance of n-type PbTe and relevant telluride by reducing vacancies and other defects.
ABSTRACT
Adhesive hydrogel-based evaporative cooling, which necessitates no electricity input, holds promise for reducing energy consumption in thermal management. Herein, inspired by the surface attachment of mussel adhesive proteins via abundant dynamic covalent bonds and noncovalent interactions, we propose a facile strategy to fabricate a self-adhesive cooling hydrogel (Li-AA-TA-PAM) using a copolymer of acrylamide (AM) and acrylic acid (AA) as the primary framework. The monomers formed hydrogen bonds between their carboxyl and amide groups, while tannic acid (TA), rich in catechol groups, enhances the adhesion of the hydrogel through hydrogen bonding. The hydrogel demonstrated strong adhesion to various material surfaces, including plastic, ceramic, glass, and metal. Even under high-speed rotation, it still maintains robust adhesion. The adhesion strength of the Li-AA-TA-PAM hydrogel to aluminum foil reached an impressive value of 296.875 kPa. Interestingly, the excellent contact caused by robust adhesion accelerates heat transfer, resulting in a rapid cooling performance, which mimics the perspiration of mammals. Lithium bromide (LiBr) with hydroactively sorptive sites is introduced to enhance sorption kinetics, thereby extending the effective cooling period. Consequently, the operation temperature of commercial polycrystalline silicon solar cells was reduced by 16 °C under an illumination of 1 kW m-2, and the corresponding efficiency of energy conversion was increased by 1.14%, thereby enhancing the output properties and life span of solar cells. The strategy demonstrates the potential for refrigeration applications using viscous gels.
ABSTRACT
This study aimed to assess the effect of pyridoxine supplementation in the mandarin fish diet on growth performance, protein and lipid metabolism, and liver and intestinal histology. Mandarin fish were fed six diets with different levels of pyridoxine (2.67 mg/kg (control), 4.41 mg/kg, 6.57 mg/kg, 10.25 mg/kg, 17.93 mg/kg, 33.12 mg/kg diet) for 8 weeks, and samples were collected for analysis. The findings demonstrated that feeding mandarin fish a diet with 6.57 mg/kg pyridoxine led to a significant increase in weight gain rate (WGR), protein efficiency ratio (PER), whole-body crude protein, whole-body crude lipid, serum protein, cholesterol (CHO), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and alkaline phosphatase (ALP), as well as significantly lower serum glucose (GLU) and feed conversion ratio (FCR), compared to the control group (P < 0.05). Furthermore, we found a significant upregulation of the relative expression of genes associated with hepatic lipid oxidation and synthesis (hl, lpl, pparα, cpt1, cs, srebp1, and fas) and proteolysis (ast, alt, and gdh) in fish fed a diet containing 6.57 mg/kg pyridoxine (P < 0.05). Regarding the histological analysis, we observed a notable decrease in the quantity of intestinal mucus-secreting cells when the fish fed a diet containing 10.25 mg/kg pyridoxine (P < 0.05). These findings suggest that dietary pyridoxine supplementation promotes mandarin fish growth by improving the efficiency of protein and lipid utilization. Additionally, we used a broken-line regression analysis to estimate the optimal dietary pyridoxine requirement for mandarin fish in the range of 6.17-6.41 mg/kg based on WGR, FCR, and PER.
Subject(s)
Diet , Pyridoxine , Animals , Pyridoxine/pharmacology , Diet/veterinary , Triglycerides/metabolism , Fishes/metabolism , Cholesterol , Dietary Supplements , Animal Feed/analysis , Lipid MetabolismABSTRACT
IMPORTANCE: Anti-programmed cell death 1 (anti-PD-1) immunotherapy features a durable response and improved survival in a small subset of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). The association between plasma Epstein-Barr virus (EBV) DNA titer dynamics and efficacy of anti-PD-1 monotherapy has been reported, while its value in predicting long-term outcomes and monitoring disease progression is unclear for patients with RM-NPC who are receiving anti-PD-1 monotherapy. OBJECTIVE: To evaluate the role of plasma EBV DNA titers in prognosis prediction and surveillance of disease progression for patients with RM-NPC who are receiving anti-PD-1 monotherapy. DESIGN, SETTING, AND PARTICIPANTS: Patients with RM-NPC from the POLARIS-02 prospective clinical trial, the largest cohort to receive anti-PD-1 monotherapy, were included in this study. From December 22, 2016, to February 19, 2019, 17 participating centers in China screened 279 patients with RM-NPC; 190 patients were enrolled and followed up until February 19, 2020. Plasma EBV DNA was detected before treatment and every 4 weeks until disease progression. MAIN OUTCOMES AND MEASURES: Plasma EBV DNA as a predictor for progression-free survival (PFS), overall survival (OS), durable clinical benefit (defined as PFS of ≥6 months), and disease progression. RESULTS: Of 179 patients with RM-NPC receiving anti-PD-1 therapy, 148 (82.7%) were men, and the median age was 46 years (range, 22-71 years). A higher baseline EBV DNA titer was associated with shorter median OS (hazard ratio, 1.88; 95% CI, 1.22-2.89; P = .004). Patients with a ratio of the EBV DNA titer at week 4 to that at baseline (W4 to baseline ratio) greater than 0.5 had shorter median OS (hazard ratio, 2.18; 95% CI, 1.30-3.65; P < .001) than those with a W4 to baseline ratio of 0.5 or less. Patients with higher baseline EBV DNA titers had a lower durable clinical benefit rate than those with lower baseline EBV DNA titers (19 of 97 [19.6%] vs 27 of 71 [38.0%]; P = .01). Similarly, patients with a W4 to baseline ratio greater than 0.5 had a lower durable clinical benefit rate than those with a W4 to baseline ratio of 0.5 or less (9 of 86 [10.5%] vs 32 of 54 [59.3%]; P < .001). In addition, a significant EBV DNA titer increase was present at a median of 2.6 months (IQR, 0.9-4.5 months) prior to radiographic progression. CONCLUSIONS AND RELEVANCE: This study of plasma EBV DNA in patients with RM-NPC who are receiving anti-PD-1 monotherapy suggests that plasma EBV DNA could be a useful biomarker for outcomes and monitoring disease progression.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Adult , Aged , DNA, Viral , Disease Progression , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/pathology , Female , Herpesvirus 4, Human/genetics , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Male , Middle Aged , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Neoplasm Recurrence, Local , Prospective Studies , Young AdultABSTRACT
Cortinarius subsalor and C. tibeticisalor, belonging to the section Delibuti, are described from China as new to science. Cortinarius subsalor has been found to be associated with Lithocarpus trees in subtropical China and resembling C. salor, but it differs from the later by having slender basidiomata and the narrower basidiospores. Cortinarius tibeticisalor was collected from eastern Tibetan Plateau, associated with Abies. It differs from other species within sect. Delibuti by having olive tinge of mature or dried basidiomata and bigger basidiospores. The molecular data also support C. subsalor and C. tibeticisalor as new species. The phylogenetic analyses and biogeography of sect. Delibuti are discussed and a key to the species of this section currently known in the world is provided.
ABSTRACT
Half-Heusler alloys, which possess the advantages of high thermal stability, a large power factor, and good mechanical property, have been attracting increasing interest in mid-temperature thermoelectric applications. In this work, extra Zr-doped TiZrxNiSn samples were successfully prepared by a modified solid-state reaction followed by spark plasma sintering. It demonstrates that extra Zr doping could not only improve the power factor on account of an increase in the Seebeck coefficient but also suppress the lattice thermal conductivity originated from the strengthened phonon scattering by the superlattice nanodomains and the secondary nanoparticles. As a consequence, an increased power factor of 3.29 mW m-1 K-2 and a decreased lattice thermal conductivity of 1.74 W m-1 K-1 are achieved in TiZr0.015NiSn, leading to a peak ZT as high as 0.88 at 773 K and an average ZT value up to 0.62 in the temperature range of 373-773 K. This work gives guidance for optimizing the thermoelectric performance of TiNiSn-based alloys by modulating the microstructures on the secondary nanophases and superlattice nanodomains.
ABSTRACT
Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Lactones/pharmacology , Macrophage Activation/drug effects , Macrophages/drug effects , Macrophages/immunology , Methicillin-Resistant Staphylococcus aureus/drug effects , Pneumonia, Staphylococcal/etiology , Sesquiterpenes/pharmacology , Acute Disease , Animals , Cell Plasticity/drug effects , Cell Plasticity/immunology , Disease Models, Animal , Macrophage Activation/immunology , Macrophages/metabolism , Mice , Models, Biological , NF-kappa B/metabolism , Phosphorylation , Pneumonia, Staphylococcal/drug therapy , Pneumonia, Staphylococcal/metabolism , Pneumonia, Staphylococcal/pathology , RAW 264.7 Cells , Signal Transduction/drug effectsABSTRACT
Typhrasa is a rare genus that comprises two species and that has previously been reported only from Europe and North America. The present study expands the geographical scope of the genus by describing two new species - T. polycystis and T. rugocephala - from subtropical China. The new species are supported by morphological characteristics and phylogenetic analyses (ITS, LSU and tef-1α). The new species have very similar morphological characteristics and are 98% similar in their ITS region. However, T. rugocephala has two types of long gills at the same time, rarely fusiform pleurocystidia with rostrum. Detailed descriptions, colour photos, illustrations and a key to related species are presented in this paper.
ABSTRACT
BACKGROUND: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms. METHODS: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested. RESULTS: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs. CONCLUSION: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
ABSTRACT
BACKGROUND: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. METHODS: we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. RESULTS: Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. CONCLUSIONS: These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
Subject(s)
Acute Lung Injury/metabolism , Drowning/metabolism , Ferroptosis/physiology , NF-E2-Related Factor 2/metabolism , Seawater/adverse effects , Acute Lung Injury/etiology , Acute Lung Injury/prevention & control , Animals , Cell Line , Drowning/etiology , Drowning/prevention & control , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Respiratory Mucosa/metabolismABSTRACT
Short-chain fatty acids (SCFAs), especially propionate, originate from the fermentation of dietary fiber in the gut and play a key role in inhibiting pulmonary inflammation. Chronic inflammation may induce an epithelial-mesenchymal transition (EMT) in alveolar epithelial cells and result in fibrotic disorders. This study was designed to investigate the beneficial effect of sodium propionate (SP) on lipopolysaccharide (LPS)-induced EMT. In cultured BEAS-2B cells, the protein expression levels of E-cadherin, α-smooth muscle actin (SMA), and vimentin were 0.66 ± 0.20, 1.44 ± 0.23, and 1.32 ± 0.21 in the LPS group vs 1.11 ± 0.36 (P < 0.05), 1.04 ± 0.30 (P < 0.05), and 0.96 ± 0.13 (P < 0.01) in the LPS + SP group (mean ± standard deviation), respectively. Meanwhile, LPS-triggered inflammatory cytokines and extracellular proteins were also reduced by SP administration in BEAS-2B cells. Moreover, SP treatment attenuated inflammation, EMT, extracellular matrix (ECM) deposition, and even fibrosis in a mouse EMT model. In terms of mechanism, LPS-treated BEAS-2B cells exhibited a higher level of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) phosphorylation, which was interrupted by SP treatment. It is worth noting that the blockade of the PI3K/Akt/mTOR signaling cascade reduced the LPS-evoked EMT process in BEAS-2B cells. These results suggest that SP can block LPS-induced EMT via inhibition of the PI3K/Akt/mTOR signaling cascade, which provides a basis for possible clinical use of SP in airway and lung diseases.
Subject(s)
Epithelial-Mesenchymal Transition/drug effects , Lipopolysaccharides/pharmacology , Lung Diseases/drug therapy , Phosphatidylinositol 3-Kinase/metabolism , Propionates/administration & dosage , Proto-Oncogene Proteins c-akt/metabolism , Actins/genetics , Actins/metabolism , Animals , Cadherins/genetics , Cadherins/metabolism , Humans , Lung Diseases/genetics , Lung Diseases/metabolism , Lung Diseases/physiopathology , Male , Mice , Phosphatidylinositol 3-Kinase/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
BACKGROUND: Hypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors. Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes. Therefore, Hy may be attractive compound applicable to hypoxia-related diseases. PURPOSE: This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism. STUDY DESIGN AND METHODS: A549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot. RESULTS: We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia. CONCLUSION: Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Heme Oxygenase-1/metabolism , Quercetin/analogs & derivatives , Tumor Hypoxia/drug effects , A549 Cells , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Heme Oxygenase-1/antagonists & inhibitors , Humans , Iron/metabolism , Phosphorylation/drug effects , Protoporphyrins/pharmacology , Quercetin/administration & dosage , Quercetin/pharmacologySubject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cholestasis/complications , Curcumin/pharmacology , Hepatitis, Chronic/drug therapy , Membrane Proteins/agonists , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Bile Ducts/surgery , Cholestasis/immunology , Curcumin/therapeutic use , Disease Models, Animal , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/immunology , Heme Oxygenase-1/metabolism , Hepatitis, Chronic/immunology , Hepatitis, Chronic/pathology , Humans , Ligation , Lipid Metabolism/drug effects , Lipid Metabolism/immunology , Liver/drug effects , Liver/immunology , Liver/pathology , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/immunology , Membrane Proteins/metabolism , Mice , Protoporphyrins/administration & dosageABSTRACT
BACKGROUND: Previous animal experiments and small human studies suggest that urinary plasmin can activate the epithelial sodium channel (ENaC) and contribute to sodium retention in nephrotic syndrome (NS), but this however is not well studied in clinical settings, and its relevance to edema formation is not well characterized in humans. We have investigated the association between urinary plasmin and clinical phenotypes in a large group of patients with NS from multiple etiologies, aiming to assess the role of urinary plasmin in sodium handling and edema formation. METHODS: Two hundred and three NS patients with urine and blood samples were divided into mild and severe symptom groups based on their edema severity. Twenty six of them had serial samples collected during the course of immunosuppressive therapy. The plasminogen-plasmin level and other key parameters were assayed, and their association with clinical manifestations were analyzed. RESULTS: One hundred and one of the 203 patients had renal biopsies performed, the results of which had included all the common types of primary NS and various types of secondary NS. Quantitative comparison and multivariate logistic regression analysis identified urinary plasminogen-plasmin to creatinine ratio (uPLG-PL/C), serum albumin, D-Dimer, and cardiac dysfunction history, but not albuminuria or 24-h urine protein, as independent risk factors for edema (p < 0.01). In patients who were treated and had serial samples, a decrease in uPLG-PL/C was identified as an independent influencing factor of edema remission (p < 0.01). Finally, the urinary fractional excretion of sodium (FENa) in patients was inversely correlated with the fractional excretion of potassium (FEK; p< 0.001), and FEK/FENa ratio was positively correlated with uPLG-PL/C (p < 0.001), suggesting a close association between uPLG-PL and ENaC activation. CONCLUSIONS: Our study identifies uPLG-PL abundance as an independent influencing factor of edema in adult NS patients, and supports the conclusion that plasmin-dependent ENaC activation is an important pathophysiological mechanism of sodium retention and edema formation in humans with NS.
Subject(s)
Edema/epidemiology , Epithelial Sodium Channels/metabolism , Fibrinolysin/urine , Nephrotic Syndrome/complications , Plasminogen/urine , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Edema/etiology , Edema/pathology , Edema/urine , Female , Fibrinolysin/metabolism , Glomerular Filtration Rate/physiology , Humans , Kidney/pathology , Kidney/physiopathology , Male , Middle Aged , Nephrotic Syndrome/pathology , Nephrotic Syndrome/physiopathology , Nephrotic Syndrome/urine , Potassium/metabolism , Renal Elimination/physiology , Risk Factors , Sodium/metabolism , Young AdultABSTRACT
OBJECTIVE: Heme oxygenase-1 (HO-1) plays a critical protective role in various insults-induced acute lung injury (ALI) through its strong anti-inflammatory, anti-oxidant, and anti-apoptotic properties, but its protective role and mechanism on seawater aspiration-induced acute lung injury remains unclear. This study aimed to explore the therapeutic potential and mechanism of HO-1 to attenuate seawater aspiration-induced ALI in vivo and in vitro. METHODS: The viability and invasion of A549 cell were analyzed through cell counting kit-8 and lactate dehydrogenase release assay; the transcriptional level of inflammatory cytokines (TNF-α, IL-6, IL-8 and MCP-1) and cell proliferation-related cytokines (FoxM1, Ccnb1 and Cdc25C) in seawater-treated A549 cell were tested by qPCR; apoptotic cells were analyzed by flow cytometryd; HO-1mRNA and protein were determined by qPCR and western blotting; the fluorescent indicators (DCFH-DA, dihydroethidium, MitoSox Red and Fluo-4) were used to monitor generation of ROS and mitochondrial function. The lung wet/dry weight radio and lactate dehydrogenase activity, Sirius red staining, TUNEL assay and immunohistochemical staining with anti-pan Cytokeratin antibody were analyzed in seawater-drowning mice. The role of HO-1 on seawater-drowning pulmonary injury was explored via HO-1 activity inhibitors (Zinc protoporphyrin) in vitro and in vivo. RESULTS: Seawater exposure decreased the cellular viability, increased the production of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α), induced cellular apoptosis and inhibited the expression of cell proliferation-related cytokines (FoxM1, Ccnb1 and Cdc25C). Moreover, seawater exposure led to mitochondrial dysfunction in A549 cells. Supplement of HO-1 sepcific inducer (heme) or its catalytic product (biliverdin) significantly attenuated seawater-induced A549 damage and promoted cell proliferation. However, Zinc protoporphyrin abolished the beneficial effects of HO-1 on seawater drowning-induced pulmonary tissue injury. CONCLUSION: HO-1 attenuates seawater drowning-induced lung injury by its anti-inflammatory, anti-oxidative, and anti-apoptosis function.
Subject(s)
Acute Lung Injury/metabolism , Drowning/metabolism , Heme Oxygenase-1/metabolism , A549 Cells , Animals , Biliverdine/metabolism , Cell Proliferation , Cytokines/genetics , Humans , Inflammation/metabolism , Male , Mice, Inbred BALB C , Oxidative Stress , SeawaterABSTRACT
OBJECTIVE: Resident alveolar macrophages (AMs) are activated and release proinflammatory mediators and chemokines during acute lung injury. We have previous reported that caveolin-1 (Cav-1) scaffolding domain (CSD) peptide inhibited the proinflammatory cytokines expression by up-regulating heme oxygenase-1 (HO-1) activity. In this study, we aimed to investigate the effect of residue R101 in CSD peptide on the activity of HO-1 in AMs. METHODS: The binding mode between HO-1 and CSD peptides (WT CSD and Δ101 CSD truncation peptides) was analyzed and the free energy was calculated. The inflammatory genes and M1/M2macrophage polarization-associated genes expression were measured by real-time PCR. The activities of HO-1 were determined by the spectrophotometical method. Western blot analyzed the content of Cav-1, HO-1, IκB and MAPK signals (phosphorylated ERK, JNK and p38 MAPK). RESULTS: Δ101CSD peptide could bind to HO-1 protein and to disrupt the interaction of HO-1 and Cav-1. However, Δ101CSD peptide had lower activity of HO-1 in LPS-treated AMs compared with WT CSD. The expression of IL-1ß and MCP-1 and NO content were decreased by WT CSD peptide in LPS treated AMs. However, only MCP-1 expression and NO content were downregulated byΔ101CSD peptide. Meanwhile, compared with those in LPSâ¯+â¯heminâ¯+â¯WT CSD group, the mRNA expression of TNF-α, Cd86, IL-12b and NOS2 significantly increased while expression of IL10, Arg1 and CD163 significantly decreased in LPSâ¯+â¯heminâ¯+â¯Δ101CSD group. The effect of WT CSD peptide on the inhibition of MAPK signaling pathway were stronger than Δ101 CSD peptide evidenced by the level of phosphorylated ERK, JNK and p38 MAPK. CONCLUSION: Deletion of residue R101 impairs the ability of CSD peptide to increase HO-1 activity and to dampen inflammatory response in LPS-challenged rat AMs.
Subject(s)
Caveolin 1/pharmacology , Heme Oxygenase-1/metabolism , Macrophages, Alveolar/drug effects , Peptide Fragments/pharmacology , Animals , Cytokines/metabolism , Heme Oxygenase-1/genetics , Macrophages, Alveolar/metabolism , Male , Mitogen-Activated Protein Kinases/metabolism , Molecular Docking Simulation , Rats, Sprague-DawleyABSTRACT
Innovative dual detection methods for mercury(II) ions (Hg(II)) have been developed based on the formation of gold nanostructures (AuNSs) following the addition of mercury-containing solution to a mixture containing an optimized amount of Au(III), H2O2, HCl, and silver nanoparticles (AgNPs). In the absence of Hg(II), the addition of Au(III), H2O2, and HCl to the AgNP solution changes the solution's color from yellow to red, and the absorption peak shifts from 400 to 526nm, indicating the dissolution of AgNPs and the formation of gold nanoparticles (AuNPs). Because of the spontaneous redox reaction of Hg(II) toward AgNPs, the change in the amount of remaining AgNP seed facilitates the generation of irregular AuNSs, resulting in changes in absorption intensity and shifting the peak within the range from 526 to 562nm depending on the concentration of Hg(II). Under optimal conditions, the limit of detection (LOD) for Hg(II) at a signal-to-noise ratio (S/N) of 3 was 0.3µM. We further observed that AgNP-assisted catalytic formation of Au nanomaterials deposited on a surface enhanced Raman scattering active substrate significantly reduced the Raman signal of 4-mercaptobenzoic acid, dependent on the Hg(II) concentration. A linear relationship was observed in the range 0.1nM-100µM with a LOD of 0.05nM (S/N 3.0). As a simple, accurate and precise method, this SERS-based assay has demonstrated its success in determining levels of Hg(II) in real water samples.
ABSTRACT
Although methylene blue (MB) has showed strong antioxidant effect, its effect related with heme oxygenase-1 (HO-1) is still unclear. Thus, we investigated the effects of MB on HO-1 protein content and enzyme activity, and its protective effect against hydrogen peroxide (H2O2)-induced oxidative damage in RAW264.7 macrophage. The cell viability and the release of lactate dehydrogenase of RAW264.7 were determined. The mitochondrial functions were valuated through these indexes: content of adenosine triphosphate, superoxide dismutase, concentration of reactive oxygen species and mitochondrial membrane potential. Meanwhile, high content screening tested generation of ROS, MMP and intracellular concentration of calcium ion. qRT-PCR valuated macrophage phenotype markers expression. Lastly, flow cytometry and caspase-3 detection analyzed RAW264.7 apoptosis. Our data showed that (1) Both pretreatment and posttreatment of MB increased HO-1 protein content and enzyme activity; (2) MB rescued cells from H2O2-induced mitochondrial dysfunction; (3) High content screening revealed that MB alleviated the changes including generation of reactive oxygen species, mitochondrial membrane potential and intracellular concentration of calcium ion in H2O2 exposed RAW264.7; (4) MB attenuated H2O2-induced apoptosis; (5) MB pretreatment decreased the expression of M1 macrophage markers (Tnf and Nos2) while increasing the expression of M2 macrophage markers (Mrc1 and Il10); (6) The beneficial effect of MB was abolished by zinc protoporphyrin IX (HO-1 activity inhibitor) or HO-1 siRNA. In summary, MB protects RAW264.7 cells from H2O2-induced injury through up-regulation HO-1.