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Purpose: The prognosis of infiltrative hepatocellular carcinoma (HCC) is dismal. Hepatic arterial infusion chemotherapy (HAIC) plus Lenvatinib (Len) and immune checkpoint inhibitor (ICI) have shown promising results for HCC. However, this three combination therapy on infiltrative HCC is unknown. In this study, we compared HAIC plus lenvatinib (Len) and programmed cell death protein-1 (PD-1) inhibitor with HAIC plus Len for infiltrative HCC. Patients and Methods: This multi-center cohort study included patients with infiltrative HCC who received HAIC combined with Len (HAIC+Len group, n = 173) or HAIC combined with Len and PD-1 inhibitor (HAIC+Len+ICI group, n = 128) as the first-line treatment from January 2019 to December 2021. To balance any intergroup differences, one-to-one propensity score matching (PSM) was applied. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups. Results: After PSM, the median OS was 14.1 ± 1.0 and 16.1 ± 1.4 months in the HAIC+Len and HAIC+Len+ICI groups, respectively. The median PFS was 4.6 ± 0.4 months in the HAIC+Len group and 7.5 ± 0.8 months in the HAIC+Len+ICI group. The HAIC+Len+ICI group showed significantly better OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.90; P = 0.008) and PFS (HR, 0.53; 95% confident index [CI], 0.40-0.70; P < 0.001) compared with the HAIC+Len group. Subgroup analysis revealed that for OS in HCC without metastasis, the addition of PD-1 inhibitor was not significant (HR, 0.68; 95% CI, 0.43-1.07; P = 0.091). No difference was observed in OS between low (2-3 cycles) and high (4-6 cycles) level of HAIC cycles (HR, 0.99; 95% CI, 0.67-1.44; P = 0.938). Conclusion: The HAIC+Len+ICI group had a longer PFS and OS compared with the HAIC+Len group, demonstrating an acceptable safety profile. This triple combination strategy may be an alternative treatment for infiltrative HCC management.
The evidence of HAIC plus Len and PD-1 inhibitors for infiltrative HCC is limited. There was no study to evaluate the efficacy of HAIC combined with Len and PD-1 inhibitors for infiltrative HCC. In this study, we found that HAIC plus Len and PD-1 inhibitor (HAIC+Len+ICI) was associated with longer progression-free survival and overall survival than HAIC plus Len combination (HAIC+Len) for patient with infiltrative HCC. In addition, OS in patients with metastasis was improved with HAIC+Len+ICI treatment. OS in patients without metastasis, addition of PD-1 inhibitor after HAIC and Len was not beneficial. What's more, three cycles of HAIC are adequate, especially for patients with high tumor burden, especially with main branch portal vein tumor thrombus (PVTT). Our research provides new evidence that HAIC+Len+ICI treatment significantly improved the OS and PFS of infiltrative HCC patients compared with those who received HAIC+Len treatment. It provides a strong reference for clinical treatment.
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Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.
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Cobre , Modelos Animais de Doenças , Macrófagos Alveolares , Oligopeptídeos , Estresse Oxidativo , Peroxirredoxina VI , Silicose , Animais , Silicose/tratamento farmacológico , Silicose/metabolismo , Silicose/patologia , Camundongos , Cobre/química , Oligopeptídeos/farmacologia , Peroxirredoxina VI/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/patologia , Humanos , Masculino , Antioxidantes/farmacologiaRESUMO
In recent years, asphalt pavement has been subjected to varied environmental conditions during its service life, conditions that predispose it to deformation and cracking. To enhance the performance of asphalt pavement, rock asphalt has been selected as a modifier due to its good compatibility with virgin asphalt binder and its ability to improve the fatigue cracking resistance of asphalt mixtures. Although scholars have conducted some studies on rock asphalt mixtures, research on the fatigue and self-healing performance of these mixtures under conditions such as ultraviolet (UV) aging and freeze-thaw remains limited. This paper presents findings from a study that employs a combined fatigue-healing test to assess the impact of such complex environmental factors on the fatigue and self-healing properties of fine aggregate matrix (FAM) mixtures containing three types of rock asphalts, i.e., Buton, Qingchuan (QC), and Uintaite Modifier (UM). The analysis of fatigue-healing test results, grounded in viscoelastic continuum damage (VECD) theory, indicates that rock asphalt can extend the fatigue life of FAM mixtures, albeit with a concomitant decrease in their self-healing capabilities. The study further reveals that UV aging, freeze-thaw, and UV aging-freeze-thaw conditions all led to a diminution in the fatigue and self-healing properties of FAM mixtures. However, FAM mixtures containing rock asphalt demonstrated greater resilience against these reductions. Atomic force microscope (AFM) results indicate that UV aging reduced the number of bee-structures and enlarged their area, whereas the incorporation of rock asphalt enhanced the uniformity of these structures' distribution, thereby improving the fatigue cracking resistance of FAM mixtures. Fourier transform infrared spectroscopy (FTIR) analysis reveals that while UV aging increased the carbonyl and sulfoxide indices within the asphalt binder, rock asphalt is effective in mitigating this effect to a certain degree, thereby enhancing the aging resistance of FAM mixtures.
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BACKGROUND: Recent studies have emphasized the importance of the biological processes of different forms of cell death in tumor heterogeneity and anti-tumor immunity. Nonetheless, the relationship between cuproptosis and lung adenocarcinoma (LUAD) remains largely unexplored. METHODS: Data for 793 LUAD samples and 59 normal lung tissues obtained from TCGA-LUAD cohort GEO datasets were used in this study. A total of 165 LUAD tissue samples and paired normal lung tissue samples obtained from our hospital were used to verify the prognostic value of dihydrolipoamide S-acetyltransferase (DLAT) and dihydrolipoamide branched chain transacylase E2 (DBT) for LUAD. The cuproptosis-related molecular patterns of LUAD were identified using consensus molecular clustering. Recursive feature elimination with random forest and a tenfold cross-validation method was applied to construct the cuproptosis score (CPS) for LUAD. RESULTS: Bioinformatic and immunohistochemistry (IHC) analyses revealed that 13 core genes of cuproptosis were all significantly elevated in LUAD tissues, among which DBT and DLAT were associated with poor prognosis (DLAT, HR = 6.103; DBT, HR = 4.985). Based on the expression pattern of the 13 genes, two distinct cuproptosis-related patterns have been observed in LUAD: cluster 2 which has a relatively higher level of cuproptosis was characterized by immunological ignorance; conversely, cluster 1 which has a relatively lower level of cuproptosis is characterized by TILs infiltration and anti-tumor response. Finally, a scoring scheme termed the CPS was established to quantify the cuproptosis-related pattern and predict the prognosis and the response to immune checkpoint blockers of each individual patient with LUAD. CONCLUSION: Cuproptosis was found to influence tumor microenvironment (TME) characteristics and heterogeneity in LUAD. Patients with a lower CPS had a relatively better prognosis, more abundant immune infiltration in the TME, and an enhanced response to immune checkpoint inhibitors.
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Adenocarcinoma de Pulmão , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Feminino , Biomarcadores Tumorais/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-IdadeRESUMO
Hepatocellular carcinoma (HCC), one of the most prevalent cancers globally, is closely associated with tumor-associated macrophages (TAMs), including monocyte-derived macrophages and liver-resident Kupffer cells. Understanding TAM heterogeneity at the cellular level is crucial for developing effective HCC prevention and treatment strategies. In this study, we conducted an integrated single-cell analysis of four cohorts (GSE140228, GSE125449, GSE149614 and GSE156625) to elucidate the TAM landscape in HCC. We identified 284 gene markers, termed Panmyeloid markers, that characterize myeloid cells within this context. Our analysis distinguished six clusters of monocyte-derived macrophages (Macro1-Macro6) and four clusters of Kupffer cells (Kupffer1-Kupffer4). Notably, CXCL10 + macrophages and MT1G + Kupffer cells, predominantly located within tumor tissues, exhibited distinct functional characteristics relevant to HCC. We also explored cellular communication between TAMs and T cells, uncovering potential signaling pathways such as the CXCL10/CXCL11-CXCR3 and CXCL12-CXCR4 networks. These findings enhance our understanding of TAMs in HCC and open new avenues for targeted therapeutic interventions.
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Lipossarcoma , Artéria Pulmonar , Neoplasias Vasculares , Humanos , Artéria Pulmonar/patologia , Artéria Pulmonar/diagnóstico por imagem , Lipossarcoma/patologia , Lipossarcoma/diagnóstico por imagem , Neoplasias Vasculares/patologia , Neoplasias Vasculares/diagnóstico por imagem , Masculino , Invasividade Neoplásica , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , IdosoRESUMO
The aim to investigate the predictive efficacy of automatic breast volume scanner (ABVS), clinical and serological features alone or in combination at model level for predicting HER2 status. The model weighted combination method was developed to identify HER2 status compared with single data source model method and feature combination method. 271 patients with invasive breast cancer were included in the retrospective study, of which 174 patients in our center were randomized into the training and validation sets, and 97 patients in the external center were as the test set. Radiomics features extracted from the ABVS-based tumor, peritumoral 3 mm region, and peritumoral 5 mm region and clinical features were used to construct the four types of the optimal single data source models, Tumor, R3mm, R5mm, and Clinical model, respectively. Then, the model weighted combination and feature combination methods were performed to optimize the combination models. The proposed weighted combination models in predicting HER2 status achieved better performance both in validation set and test set. For the validation set, the single data source model, the feature combination model, and the weighted combination model achieved the highest area under the curve (AUC) of 0.803 (95% confidence interval [CI] 0.660-947), 0.739 (CI 0.556,0.921), and 0.826 (95% CI 0.689,0.962), respectively; with the sensitivity and specificity were 100%, 62.5%; 81.8%, 66.7%; 90.9%,75.0%; respectively. For the test set, the single data source model, the feature combination model, and the weighted combination model attained the best AUC of 0.695 (95% CI 0.583, 0.807), 0.668 (95% CI 0.555,0.782), and 0.700 (95% CI 0.590,0.811), respectively; with the sensitivity and specificity were 86.1%, 41.9%; 61.1%, 71.0%; 86.1%, 41.9%; respectively. The model weighted combination was a better method to construct a combination model. The optimized weighted combination models composed of ABVS-based intratumoral and peritumoral radiomics features and clinical features may be potential biomarkers for the noninvasive and preoperative prediction of HER2 status in breast cancer.
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Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Neoplasias da Mama/diagnóstico por imagem , Radiômica , Estudos Retrospectivos , MamaRESUMO
Objective: Adalimumab (ADA) is an effective treatment for inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD). The equal effect between the original ADA and biosimilars from Europe and the United States has been shown. However, the biosimilar of ADA is different in China. The effectiveness and safety data of ADA biosimilar (HS016) in China have yet to be discovered. Patients and methods: 91 patients (75 CD, 16 UC) received HS016 treatment and were enrolled in this study. Therapeutic response and safety profiles were analyzed. Therapeutic drug monitoring (TDM) was also carried out among nonresponse patients. After being considered as "nonresponse" (after three or 6 months of treatment), 20 patients' serum TNFα concentrations were measured and correlated to their disease severity. Results: Among active CD patients (n = 61), 75.4% (46/61) at 12 w, 73.8% (45/61) at 26 w, 50.8% (31/61) at 52 w achieved the clinical response, respectively; 55.7% (34/61) at 12 w, 65.6% (40/61) at 26 w, and 45.9% (28/61) at 52 w achieved clinical remission. The maintained remission rates of CD (n = 14) in clinical remission were 100% (14/14) at 12 w, 78.6% (11/14) at 26 w, and 63.6% (7/11) at 52 w, respectively. Among active UC patients, 37.5% (6/16) at 12 w and 50% (8/16) at 26 w achieved clinical response. Total adverse event rates were 5.5% (5/91) during 52-week visits. Due to the inadequate serum drug concentration, 30.4% (7/23) of patients had poor clinical responses. Elevations of serum anti-drug antibodies occurred in one additional patient (4.3%). Conclusion: ADA biosimilar HS016 had good efficacy and safety in Chinese IBD patients.
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Objective: To investigate the association between thyroid functions and the oral microbiome diversity. Method: Data from the US National Health and Nutrition Examination Survey (NHANES; 2009-2012) were analyzed. Thyroid functions were defined using thyroid hormones and related biomarkers. Oral microbiome was measured using the observed number of amplicon sequence variants (ASVs) and the Bray-Curtis dissimilarity. Linear regression was used to estimate the average change (ß) and 95% CI for the number of ASVs against thyroid functions, adjusted for sociodemographic variables, health conditions, urinary iodine status, and periodontitis. Non-metric multidimensional scaling (NMDS) was used to analyze the Bray-Curtis dissimilarity. Results: A total of 2943 participants were analyzed. The observed number of ASVs has a weighted mean of 128.9. Self-reported thyroid disease was associated with reduced number of ASVs (ß = -9.2, 95% CI: -17.2, -1.2), if only adjusted for sociodemographic variables and health conditions. In the fully adjusted model, compared to normal thyroid function, both subclinical and clinical hyperthyroidism were associated with reduced number of ASVs (ß = -59.6, 95% CI: -73.2, -46.0; ß = -28.2, 95% CI: -50.0, -6.5, respectively). Thyroid peroxidase antibody level higher than the reference range was associated with higher observed ASV (ß= 9.0, 95% CI: 1.2, 16.9). NMDS analysis suggested significant difference in oral microbiome composition between free triiodothyronine groups (P = .002), between free thyroxine groups (P = .015), and between thyroglobulin groups (P = .035). Conclusion: Hyperthyroidism was associated with reduced oral microbiome diversity. Free triiodothyronine, free thyroxine, and thyroglobulin levels may alter the oral microbiome composition.
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Studies have documented that per- and polyfluoroalkyl substance (PFAS) exposures are associated with thyroid hormones (TH) and lipid levels. This study investigates whether these effects interfere with each other. We analyzed data on 3954 adults in the US National Health and Nutrition Examination Survey (NHANES; 2007-2012). TH disorder was defined using thyroid hormones. Serum high-density lipoprotein (HDL) cholesterol, total cholesterol, and six types of PFAS were included. Weighted quantile sum (WQS) regression was used to estimate the overall effect of PFAS mixture on TH disorder and cholesterols, respectively. Potential confounders, including age, race, gender, education, household poverty, smoking, and alcohol drinking, were adjusted. PFAS mixture was associated increased risk for TH disorder (odds ratio = 1.21, 95% confidence interval (CI): 1.02, 1.43), higher HDL cholesterol (linear coefficient = 1.31, 95% CI: 0.50, 2.11), and higher total cholesterol (linear coefficient = 5.30, 95% CI: 3.40, 7.21). TH disorder was associated with higher HDL cholesterol (linear coefficient = 2.30, 95% CI: 0.50, 2.11), but not total cholesterol. When adjusted for TH disorder, the effect estimates of PFAS mixture remain roughly unchanged on HDL cholesterol (linear coefficient = 1.13, 95% CI: 0.28, 1.98) and total cholesterol (linear coefficient = 5.61, 95% CI: 3.58, 7.63). Sex modified the effect of PFAS mixture on HDL cholesterol (P for interaction: 0.04) but did not change the interaction between PFAS and TH disorder on cholesterols. We corroborated the adverse health effects of PFAS exposure on TH and lipids; however, these two effects appear to be independent of and not interfere with each other.
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Ácidos Alcanossulfônicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Poluentes Ambientais , Fluorocarbonos , Adulto , Humanos , Inquéritos Nutricionais , HDL-Colesterol , Hormônios Tireóideos , ColesterolRESUMO
Designing definite transition metal heterointerfaces is considered an effective strategy for the construction of efficient and robust oxygen evolution reaction (OER) electrocatalysts, but rather challenging. Herein, amorphous NiFe hydr(oxy)oxide nanosheet arrays (A-NiFe HNSAs) are grown in situ on the surface of a self-supporting Ni metal-organic frameworks (SNMs) electrode via a combination strategy of ion exchange and hydrolytic co-deposition for efficient and stable large-current-density water oxidation. The existence of the abundant metal-oxygen bonds on the heterointerfaces can not only be of great significance to alter the electronic structure and accelerate the reaction kinetics, but also enable the redistribution of Ni/Fe charge density to effectively control the adsorption behavior of important intermediates with a close to the optimal d-band center, dramatically narrowing the energy barriers of the OER rate-limiting steps. By optimizing the electrode structure, the A-NiFe HNSAs/SNMs-NF exhibits outstanding OER performance with small overpotentials of 223 and 251 mV at 100 and 500 mA cm-2 , a low Tafel slope of 36.3 mV dec-1 , and excellent durability during 120 h at 10 mA cm-2 . This work significantly provides an avenue to understand and realize rationally designed heterointerface structures toward effective oxygen evolution in water-splitting applications.
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Objective: Behçet's Disease (BD) is an intractable systemic vasculitis. When accompanied by intestinal symptoms, the prognosis is usually poor. 5-Aminosalicylic acid (5-ASA), corticosteroids, immunosuppressive drugs, and anti-tumor necrosis factor-α (anti-TNF-α) biologics are standard therapies to induce or maintain remission for intestinal BD. However, they might not be effective in refractory cases. Safety should also be considered when patients have an oncology history. Regarding the pathogenesis of intestinal BD and the specific targeting effect of vedolizumab (VDZ) on the inflammation of the ileum tract, previous case reports suggested that VDZ might be a potential treatment for refractory intestinal BD. Methods: We report a 50-year-old woman patient with intestinal BD who had oral and genital ulcers, joint pain, and intestinal involvement for about 20 years. The patient responds well to anti-TNF-α biologics but not to conventional drugs. However, biologics treatment was discontinued due to the occurrence of colon cancer. Results: VDZ was intravenously administered at a dose of 300 mg at 0, 2, and 6 weeks and then every eight weeks. At the 6-month follow-up, the patient reported significant improvement in abdominal pain and arthralgia. We observed complete healing of intestinal mucosal ulcers under endoscopy. However, her oral and vulvar ulcers remained unresolved, which disappeared after adding thalidomide. Conclusion: VDZ may be a safe and effective option for refractory intestinal BD patients who do not respond well to conventional treatments, especially those with an oncology history.
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Síndrome de Behçet , Produtos Biológicos , Enteropatias , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Úlcera/tratamento farmacológico , Úlcera/etiologia , Fator de Necrose Tumoral alfa/uso terapêutico , Fatores Biológicos/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
Celecoxib is a sulfanilamide nonsteroidal anti-inflammatory drug that can selectively inhibit cyclooxygenase-2 to inhibit prostaglandin production, achieving anti-inflammatory and analgesic effects. This study investigated the pharmacokinetics, safety, and bioequivalence of a single oral dose of celecoxib capsule (the test or reference preparation) in healthy volunteers under fasting and fed conditions. A single-center, randomized, open, single-dose, double-cycle crossover self-control design was conducted: 40 healthy volunteers were enrolled in the fasting and fed groups, respectively. A completely randomized method was used, with one group taking the test celecoxib preparation (T) and the other taking the reference celecoxib preparation (R). During the administration period, the safety of the drug was evaluated simultaneously, and venous blood was collected at the corresponding time points. The concentration of celecoxib in plasma was measured by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were logarithmically converted and analyzed for variance. The 90% confidence interval for the bioavailability of the T compared to the R was calculated using maximum drug plasma concentration, area under the plasma concentration-time curve from time zero to the last quantifiable concentration point, and area under the plasma concentration-time curve from time zero to infinity for a single oral dose in volunteers, and the data obtained were all between 80% and 125%, indicating that the T and R have bioequivalence and good safety during fasting and fed administration.
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Anti-Inflamatórios , Celecoxib , População do Leste Asiático , Humanos , Anti-Inflamatórios/farmacocinética , Celecoxib/farmacocinética , Voluntários Saudáveis , Equivalência TerapêuticaRESUMO
Owing to its high throughput, simplicity, and rapidity, enzyme-linked immunosorbent assay (ELISA) has attracted much attention in the field of immunoassays. However, the traditional ELISA usually affords a single signal readout and the labeling ability of the enzyme used is poor, resulting in low accuracy and a limited detection range. Herein, a vanadium nanospheres (VNSs)-mediated competitive ratio nanozymes-linked immunosorbent assay (VNSs-RNLISA) was created for the sensitive detection of the T-2 toxin (T-2). As the key to the biosensor, the VNSs with superoxide dismutase-like and peroxidase-like dual-enzyme mimetic activities were synthesized by a one-step hydrothermal method, which oxidized 1,1-diphenyl-2-picryl-hydrazyl fading and catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) color development. Therefore, T-2 could not only be qualitatively measured with the naked eye but also be quantitatively evaluated by monitoring the ratio of absorbance at 450 and 517 nm wavelengths. Moreover, the characterization of a VNSs-labeled antibody probe showed strong dual-enzymatic activity, excellent stability, and high affinity with T-2 [the affinity constant (ka) was approximately 1.36 × 108 M-1], which can significantly improve the detection sensitivity. The limit of detection of VNSs-RNLISA was 0.021 ng/mL, which was approximately 27-fold more sensitive than the single signal nanozymes-linked immunosorbent assay (0.561 ng/mL). Besides, the change in the ratio of absorbance (Δ450/Δ517) decreased linearly in a range of 0.22-13.17 ng/mL, outperforming the detection range of a single-mode nano-enzyme-linked immunosorbent assay using TMB by a factor of 1.6 times. Furthermore, the VNSs-RNLISA was successfully used to identify T-2 in maize and oat samples, with recoveries ranging from 84.216 to 125.371%. Overall, this tactic offered a promising platform for the quick detection of T-2 in food and might broaden the application range of the enzyme-linked immunosorbent assay.
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Técnicas Biossensoriais , Nanosferas , Toxina T-2 , Imunoensaio/métodos , Vanádio , Imunoadsorventes , Limite de DetecçãoRESUMO
BACKGROUND: Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. METHODS: The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n = 11) were detected using reversed-phase high-performance liquid chromatography. The complex GHK with Cu (GHK-Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]-exposure mouse model) to explore the involvement of GHK in CS-induced skeletal muscle dysfunction. RESULTS: Compared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF-α (R = -0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK-Cu was found to rescue CSE-induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin-1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS-induced muscle dysfunction C57BL/6 mice, GHK-Cu treatment (0.2 and 2 mg/kg) reduces CS-induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P < 0.05) and muscle cross-sectional area elevated (1055 ± 552.4 µm2 vs. 1797 ± 620.9 µm2 , 2252 ± 534.0 µm2 ; P < 0.001), and also rescues CS-induced muscle weakness, indicated by improved grip strength (175.5 ± 36.15 g vs. 257.6 ± 37.98 g, 339.1 ± 72.22 g; P < 0.01). Mechanistically, GHK-Cu directly binds and activates SIRT1(the binding energy was -6.1 kcal/mol). Through activating SIRT1 deacetylation, GHK-Cu inhibits FoxO3a transcriptional activity to reduce protein degradation, deacetylates Nrf2 and contribute to its action of reducing oxidative stress by generation of anti-oxidant enzymes, increases PGC-1α expression to promote mitochondrial function. Finally, GHK-Cu could protect mice against CS-induced skeletal muscle dysfunction via SIRT1. CONCLUSIONS: Plasma glycyl-l-histidyl-l-lysine level in patients with chronic obstructive pulmonary disease was significantly decreased and was significantly associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu2+ could protect against cigarette smoking-induced skeletal muscle dysfunction via sirtuin 1.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Lisina/metabolismo , Sirtuína 1/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
Designing efficient and sensitive methods for the detection of nitrofurantoin (NFT) residues is of great importance for food safety and environmental protection. Herein, a composite with cobalt nanoparticles encapsulated in nitrogen-doped carbon nanotube (N/Co@CNTs@CC-II) was synthesized by in-situ growth and sublimation-gas phase transformation strategy and used to establish an ultrasensitive electrochemical sensor for NFT determination. The N/Co@CNTs@CC-II sensor exhibits uniform N doping, fine hollow structure, and abundant active metal sites, which lays a solid foundation for the ultra-sensitive detection of NFT. Benefiting from these advantages, the N/Co@CNTs@CC-II exhibits excellent sensitivity (8.19 µA µM-1 cm-2) and low detection limit (18.41 nM) for NFT detection. The practical feasibility of N/Co@CNTs@CC-II was also demonstrated by the determination of NFT in milk and tap water samples. This study may open up new opportunities for the application of N-doped carbon nanotube materials encapsulating transition metals.
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Nanopartículas , Nanotubos de Carbono , Cobalto/química , Nanotubos de Carbono/química , Nitrofurantoína , Nanopartículas MetálicasRESUMO
Rational engineering active sites and vantage defects of catalysts are promising but grand challenging task to enhance photoreduction CO2 to high value-added C2 products. In this study, we designed an N,S-codoped Fe-based MIL-88B catalyst with well-defined bipyramidal hexagonal prism morphology via a facile and effective process, which was synthesized by addition of appropriate 1,2-benzisothiazolin-3-one (BIT) and acetic acid to the reaction solution. Under simulated solar irradiation, the designed catalyst exhibits high C2 H4 evolution yield of 17.7â µmol g-1 â h, which has been rarely achieved in photocatalytic CO2 reduction process. The synergistic effect of Fe-N coordinated sites and reasonable defects in the N,S-codoped photocatalyst can accelerate the migration of photogenerated carriers, resulting in high electron density, and this in turn helps to facilitate the formation and dimerization of C-C coupling intermediates for C2 H4 effectively.
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Developing electrode materials with excellent electrocatalytic properties for detecting pesticide residues plays a vital role in the safety of agricultural products and environmental applications. Herein, we designed a new electrochemical sensor on the basis of N-doped carbon hollow nanospheres modified with Sn/MoC Schottky junction (Sn/MoC@NC) for methyl parathion (MP) detection. The Sn/MoC@NC was prepared by self-assembled polymerization-anchoring strategy and high-temperature carbonization design. Sn/MoC Schottky junction and hollow nanosphere structure endow Sn/MoC@NC with a larger surface area, more active sites, and faster electron transfer, which is beneficial to enhancing its electrocatalytic performance. The structural characterizations and physicochemical properties of Sn/MoC@NC were explored through various microscopy, spectroscopic and electrochemical techniques. The experimental results confirmed that the calibration curve for current and MP concentration (0.05-10 µg/mL) was available under optimized conditions, and the sensitivity and detection limit were respectively determined to be 9.02 µA µM1 cm2 and 8.9 ng/mL. Furthermore, the constructed sensor displayed excellent selectivity, repeatability, and stability, which qualified it for use in detecting MP in grapes and tap water with satisfactory recovery. This work may provide some interesting prospects for constructing high-performance electrocatalysts for MP detection.
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To obtain a green carrier for intestinal targeted delivery, an emulsion gel was designed by the self-assembly between gelatin and Pickering emulsion based on gallic acid modified-chitosan nanoparticles (GCS NPs). The emulsion gels loaded with garlic essential oil (Geo) and curcumin (Cur) were abbreviated as GOEG and GCEG, respectively. Meanwhile, the sodium alginate bead loaded with Geo (GOEGS3) and the bead loaded with Cur (GCEGS) were prepared as controls. Results demonstrated that the emulsion gels significantly improved the bioaccessibility of Geo and Cur, showing great intestinal targeting delivery properties comparable to that of sodium alginate beads. Moreover, Caco-2 cell experiments indicated that GOEG and GCEG displayed good biocompatibility and enhanced cellular uptake of Geo and Cur. The emulsion gels also exhibited excellent anti-inflammatory properties in the lipopolysaccharide-induced cell model, exhibiting great potential for clinical application. This work provides some references for the preparation of multifunctional emulsion gels with excellent delivery performance by a green method.