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OBJECTIVE: To investigate the impact of IGJ on the proliferation, inflammation, and motility of rheumatoid arthritis (RA) fibroblast-like synoviocytes and elucidate the underlying mechanism. METHODS: The expression of IGJ RA fibroblast-like synoviocytes was assessed using immunoblot and qPCR. Cell growth was evaluated using CCK-8 and FCM assays. The effects on inflammatory response were determined by ELISA and immunoblot assays. Cell motility was assessed using transwell and immunoblot assays. The mechanism was further confirmed using immunoblot assays. RESULTS: IGJ expression was found to be elevated in fibroid synovial cells of RA. IGJ ablation inhibited the growth of MH7A cells and suppressed the inflammatory response. Knockdown of IGJ also blocked cell motility. Mechanically, the knockdown of IGJ suppressed the NF-κB axis in MH7A cells. CONCLUSION: IGJ suppresses RA in fibroblast-like synoviocytes via NF-κB pathway.
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Artritis Reumatoide , Movimiento Celular , Proliferación Celular , Fibroblastos , FN-kappa B , Transducción de Señal , Sinoviocitos , Humanos , Sinoviocitos/metabolismo , Sinoviocitos/patología , Sinoviocitos/efectos de los fármacos , Artritis Reumatoide/patología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , FN-kappa B/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Células Cultivadas , Línea Celular , HialuronoglucosaminidasaRESUMEN
In this paper, we present a robotically steerable laser ablation probe with application to interstitial thermal therapy. Existing laser interstitial thermal therapy (LITT) methods utilize a straight probe to deliver laser energy around the tip or to the side of the tip. These methods are inadequate to provide effective treatment for large, irregularly shaped tumors. Our robotic probe can be manipulated inside soft tissue to perform ablation at multiple locations, thus enabling conformable ablation for large and complicated tumors. Instead of directly firing laser into soft tissue, a Polydimethylsiloxane (PDMS)/Carbon nanoparticles (CNPs) mixture hosts a multi-mode optical fiber at the probe tip to work as a heater when laser is activated to improve the procedural safety. This paper presents the design and fabrication of the robotic ablation probe, simulation of laser thermal transformation using finite element analysis, and experimental studies that characterize the robot motion and heating effects and demonstrate in vitro ablation.
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Objectives: This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods: We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion. Results: The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10-5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion. Conclusion: The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.
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Globally, streptococcal disease caused by Streptococcus agalactiae is known for its high mortality rate, which severely limits the development of the tilapia breeding industry. As a third-generation vaccine, DNA vaccines have shown great application prospects in the prevention and control of aquatic diseases, but their low immunogenicity limits their development. The combination of DNA vaccines and molecular adjuvants proved to be an effective method for inducing protective immunity. This study constructed recombinant plasmids encoding tilapia HSP70 and IL-1ß genes (pcHSP70 and pcIL-1ß) to verify their effectiveness as molecular adjuvants for S. agalactiae DNA vaccine (pcSIP) in the immunized tilapia model. The results revealed that serum-specific IgM production, enzyme activities, and immune-related gene expression in tilapia immunized with pcSIP plus pcHSP70 or pcIL-1ß were significantly higher than those in tilapia immunized with pcSIP alone. It is worth noting that combination with molecular adjuvants improved the immune protection of DNA vaccines, with a relative percentage survival (RPS) of 51.72% (pcSIP plus pcHSP70) and 44.83% (pcSIP plus pcIL-1ß), respectively, compared with that of pcSIP alone (24.14%). Thus, our study indicated that HSP70 and IL-1ß in tilapia are promising molecular adjuvants of the DNA vaccine in controlling S. agalactiae infection.
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BACKGROUND: Active rheumatoid arthritis (RA) may damage vascular endothelial cells, thereby increasing the likelihood of adverse cardiovascular events. However, it is not yet clearly established whether RA also increases the risk of adverse cerebrovascular events, particularly stroke. OBJECTIVE: This study was designed to evaluate the likelihood of a causal association between RA and stroke. METHOD: A two-sample Mendelian randomization (MR) analysis was performed using the inverse variance-weighted (IVW) average, weighted median, and MR-Egger regression methods. The analysis utilized publicly available summary statistics datasets from Genome-wide association studies (GWAS) meta-analyses for RA in individuals of European descent (total n = 484,598; case = 5427, control = 479,171) as the exposure cohort, and from GWAS meta-analyses for "vascular/heart problems diagnosed by doctor: stroke" in individuals included in the UK Biobank (total n = 461,880; case = 7055, control = 454,825, MRC-IEU consortium) as the outcome cohort. RESULTS: Eight single-nucleotide polymorphisms with genome-wide significance were selected from the GWASs on RA as the instrumental variables. The results of the MR-Egger and weighted median analyses showed no causal association between RA and stroke (OR = 1.081, 95â¯% CI [0.943-1.240], P = 0.304) vs. OR = 1.079, 95â¯% CI [0.988-1.179], P = 0.091), respectively. However, the inverse variance-weighted (IVW) analysis results revealed a causal association between RA and stroke (OR = 1.115, 95â¯% CI [1.040-1.194], P = 0.002). Cochran's Q test and MR-Egger regression revealed no evidence of heterogeneity and horizontal pleiotropy. CONCLUSION: The MR analysis results indicated that rheumatoid arthritis (RA) may be causally associated with an increased risk of stroke.
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Artritis Reumatoide , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular , Humanos , Artritis Reumatoide/genética , Artritis Reumatoide/complicaciones , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/epidemiología , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Predisposición Genética a la Enfermedad/genéticaRESUMEN
A patient with longstanding rheumatoid arthritis (RA) complained of spinal cord symptoms after RA relapse. Contrast MRI demonstrated neuromyelitis in the upper thoracic spinal cord, and anti-aquaporin-4 (anti-AQP4) antibody was positive in the serum and cerebrospinal fluid (CSF). Neuromyelitis optica spectrum disorder (NMOSD) was diagnosed after excluding central nervous system (CNS) infection and tumor, and spinal cord symptoms were relieved after high dose of glucocorticoid and immunosuppressant were initiated for treatment.
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Artritis Reumatoide , Neuromielitis Óptica , Humanos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/complicaciones , Femenino , Imagen por Resonancia Magnética , Glucocorticoides/uso terapéutico , Acuaporina 4/inmunología , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Autoanticuerpos/sangreRESUMEN
The effects of carboxylation degree (0.3-2.4 mmol/g) of cellulose nanofiber (CNF) on the microstructure and mechanical properties of edible walnut oleogels were comprehensively examined. The oleogels were well prepared by emulsion-templated approach for potential substitute of conventional saturated or trans-fats in food products. The results demonstrated that the oil-binding capacity (OBC) and textural strength of oleogels enhanced with the increase of CNF carboxyl content, while the structural strength (G' in rheological measurement) and the resistance to shear thinning was first decreased and then increased. It possibly reflected the competition on the dominant structuring mechanism by hydrogen bonding from cellulose hydroxyl groups and electrostatic interactions from -COONa function. With the combined mechanism, oleogel with low structural strength and relatively high OBC (CNF carboxyl content of 1.2 mmol/g, OBC >83 %, G' ≈ 7 × 104 Pa and firmness of 0.30 N) and oleogel with enough structural rigidity and high OBC (CNF carboxyl content of 1.8 mmol/g, OBC >89 %, G' of up to 1.7 × 105 Pa, and firmness of up to 0.66 N) were both fabricated. This reveals the feasibility of regulating oleogel structure and textual properties by using CNF as the unique oleogelator and simply changing its surface carboxyl function.
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Celulosa , Juglans , Nanofibras , Compuestos Orgánicos , Reología , Celulosa/química , Juglans/química , Compuestos Orgánicos/química , Nanofibras/químicaRESUMEN
Artificially extracted agricultural phenotype information exhibits high subjectivity and low accuracy, while the utilization of image extraction information is susceptible to interference from haze. Furthermore, the effectiveness of the agricultural image dehazing method used for extracting such information is limited due to unclear texture details and color representation in the images. To address these limitations, we propose AgriGAN (unpaired image dehazing via a cycle-consistent generative adversarial network) for enhancing the dehazing performance in agricultural plant phenotyping. The algorithm incorporates an atmospheric scattering model to improve the discriminator model and employs a whole-detail consistent discrimination approach to enhance discriminator efficiency, thereby accelerating convergence towards Nash equilibrium state within the adversarial network. Finally, by training with network adversarial loss + cycle consistent loss, clear images are obtained after dehazing process. Experimental evaluations and comparative analysis were conducted to assess this algorithm's performance, demonstrating improved accuracy in dehazing agricultural images while preserving detailed texture information and mitigating color deviation issues.
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AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
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Ácido Clorogénico , Nefropatías Diabéticas , Fibrosis , Riñón , Metabolismo de los Lípidos , Receptor Notch1 , Factor de Transcripción STAT3 , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Receptor Notch1/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Animales , Transducción de Señal/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Humanos , Ratones , Masculino , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Línea CelularRESUMEN
ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.
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Aorta , Enfermedades de la Aorta , Aterosclerosis , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Placa Aterosclerótica , Proproteína Convertasa 9 , Receptores de LDL , Sapogeninas , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Aterosclerosis/genética , Sapogeninas/farmacología , Proproteína Convertasa 9/metabolismo , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Receptores de LDL/metabolismo , Humanos , Masculino , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/prevención & control , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/tratamiento farmacológico , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Proteolisis/efectos de los fármacos , Células Hep G2 , Inhibidores de PCSK9 , Transducción de Señal/efectos de los fármacos , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Ratones , Dieta Alta en Grasa , Apolipoproteínas ERESUMEN
BACKGROUND: With the changes in lifestyle and diet structure, the incidence of obesity has increased year by year, and obesity is one of the inducements of many chronic metabolic diseases. Epigallocatechin gallate (EGCG), which is the most abundant component of tea polyphenols, has been used for many years to improve obesity and its complications. Though it has been reported that EGCG can improve obesity through many molecular mechanisms, EGCG may have many mechanisms yet to be explored. In this study, we explored other possible mechanisms through molecular docking and in vitro experiments. METHODS: AutoDock Vina was selected for conducting the molecular docking analysis to elucidate the interaction between EGCG and Notch1, while molecular dynamics simulations were employed to validate this interaction. Then, the new regulation mechanism of EGCG on obesity was verified with in vitro experiments, including a Western blot experiment, immunofluorescence experiment, oil red O staining, and other experiments in 3T3-L1 adipocytes. RESULTS: The molecular docking results showed that EGCG could bind to Notch1 protein through hydrogen bonding. In vitro cell experiments demonstrated that EGCG can significantly reduce the sizes of lipid droplets of 3T3-L1 adipocytes and promote UCP-1 expression by inhibiting the expression of Notch1 in 3T3-L1 adipocytes, thus promoting mitochondrial biogenesis. CONCLUSIONS: In this study, molecular docking and in vitro cell experiments were used to explore the possible mechanism of EGCG to improve obesity by inhibiting Notch1.
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Adipogénesis , Catequina , Simulación del Acoplamiento Molecular , Receptor Notch1 , Animales , Ratones , Células 3T3-L1 , Adipogénesis/efectos de los fármacos , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química , Regulación de la Expresión Génica/efectos de los fármacos , Simulación de Dinámica Molecular , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Receptor Notch1/metabolismo , Proteína Desacopladora 1/metabolismoRESUMEN
The present study aimed to establish an effective prognostic nomogram model based on the Naples prognostic score (NPS) for resectable thoracic esophageal squamous cell carcinoma (ESCC). A total of 277 patients with ESCC, who underwent standard curative esophagectomy and designated as study cohort, were retrospectively analyzed. The patients were divided into different groups, including NPS 0, NPS 1, NPS 2, and NPS 3 or 4 groups, for further analysis, and the results were validated in an external cohort of 122 ESCC patients, who underwent surgery at another cancer center. In our multivariate analysis of the study cohort showed that the tumor-node-metastasis (TNM) stage, systemic inflammation score, and NPS were the independent prognostic factors for the overall survival (OS) and progression-free survival (PFS) durations. In addition, the differential grade was also an independent prognostic factor for the OS in the patients with ESCC after surgery (all Pâ <â .05). The area under the curve of receiver operator characteristics for the PFS and OS prediction with systemic inflammation score and NPS were 0.735 (95% confidence interval [CI] 0.676-0.795, Pâ <â .001) and 0.835 (95% CI 0.786-0.884, Pâ <â .001), and 0.734 (95% CI 0.675-0.793, Pâ <â .001) and 0.851 (95% CI 0.805-0.896, Pâ <â .001), respectively. The above independent predictors for OS or PFS were all selected in the nomogram model. The concordance indices (C-indices) of the nomogram models for predicting OS and PFS were 0.718 (95% CI 0.681-0.755) and 0.669 (95% CI 0.633-0.705), respectively, which were higher than that of the 7th edition of American Joint Committee on Cancer TNM staging system [C-index 0.598 (95% CI 0.558-0.638) for OS and 0.586 (95% CI 0.546-0.626) for PFS]. The calibration curves for predicting the 5-year OS or PFS showed a good agreement between the prediction by nomogram and actual observation. In the external validation cohort, the nomogram discrimination for OS was better than that of the 7th edition of TNM staging systems [C-index: 0.697 (95% CI 0.639-0.755) vs 0.644 (95% CI 0.589-0.699)]. The calibration curves showed good consistency in predicting the 5-year survival between the actual observation and nomogram predictions. The decision curve also showed a higher potential of the clinical application of predicting the 5-years OS of the proposed nomogram model as compared to that of the 7th edition of TNM staging systems. The preoperative NPS-based nomogram model had a certain potential role for predicting the prognosis of ESCC patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Nomogramas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Persona de Mediana Edad , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Pronóstico , Esofagectomía/métodos , Anciano , Estadificación de Neoplasias , AdultoRESUMEN
Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.
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Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence of NAFLD by increasing the low-density lipoprotein receptor (LDLR) accumulation and alleviating cholesterol metabolism disorders. Therefore, the present study explored the effect of GA on LDLR and its mechanism of action. The findings indicated that the increase in LDLR accumulation in HepG2 cells induced by GA was associated with the stimulation of the epidermal growth factor receptor-extracellular regulated protein kinase (EGFR-ERK1/2) signaling pathway. When the pathway was inhibited by EGFR mab cetuximab, it was observed that the activation of the EGFR-ERK1/2 signaling pathway induced by GA was also blocked. At the same time, the accumulation of LDLR protein and the uptake of LDL were also suppressed. Additionally, GA can also promote the accumulation of forkhead box O3 (FOXO3) and suppress the accumulation of hepatocyte nuclear factor-1α (HNF1α), leading to the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) mRNA expression and protein accumulation. This ultimately results in increased LDLR protein accumulation and enhanced uptake of LDL in cells. In summary, the present study revealed the potential mechanism of GA's role in ameliorating NAFLD, with a view of providing a theoretical basis for the dietary supplementation of GA.
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Ácido Gálico , Lipoproteínas LDL , Receptores de LDL , Humanos , Ácido Gálico/farmacología , Receptores de LDL/metabolismo , Células Hep G2 , Lipoproteínas LDL/metabolismo , Receptores ErbB/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proproteína Convertasa 9/metabolismo , Proproteína Convertasa 9/genéticaRESUMEN
Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme Mseâ . The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 â and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.
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Cornus , Ciervos , Animales , Polimorfismo de Longitud del Fragmento de Restricción , Cornus/genética , Reacción en Cadena de la Polimerasa/métodos , Ciervos/genética , Cartilla de ADNRESUMEN
BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.
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Membranas Asociadas a Mitocondrias , Daño por Reperfusión , Humanos , Fosfatidilinositol 3-Quinasas , Proteómica , HipoxiaRESUMEN
Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the parameters in the diagnosis of anxiety and depression in PD patients. Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The generalized anxiety scale(GAD-7) and the patient health questionnaire(PHQ-9) were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were collected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW) were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients. Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0%,respectively.There were differences in the dialysis period(Z=-2.358,P=0.018;Z=-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z=-4.587,P<0.001;Z=-7.367,P<0.001) between the anxiety group and the non-anxiety group as well as between the depression group and the non-depression group.The correlation analysis showed that MPV(r=0.358,P<0.001;r=0.489,P<0.001) and PDW(r=0.340,P<0.001;r=0.447,P<0.001) were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P=0.022,P=0.011),PDW(P=0.041,P=0.018),and dialysis period(P=0.011,P=0.030) were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively. Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.
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Ansiedad , Diálisis Peritoneal , Humanos , Diálisis Peritoneal/efectos adversos , Hospitales , Modelos Logísticos , Curva ROCRESUMEN
Moringa oleifera Lam. leaves are a new raw food material rich in polysaccharides. These polysaccharides exhibit various biological properties, including antioxidant, hypoglycemic and immunoregulatory effects. However, the use of Moringa oleifera Lam. leaves polysaccharides (MOLP) may be limited by their large molecular weight (MW) and presence of numerous impurities, such as pigments. Research has indicated that degraded polysaccharides usually exhibit high biological activity because of changes in physical structure and chemical properties. In this study, we focused on the extraction of a degraded-modified fraction from MOLP using the Ultraviolet/ Hydrogen peroxide (UV/H2O2) method. Specifically, the physicochemical properties and glycosidic bond composition of a particular fraction (UV/H2O2 degraded Moringa oleifera Lam. leaves polysaccharides in 3 h called DMOLP-3) were investigated. In addition, in vitro simulated digestion experiments showed that DMOLP-3 was only partially degraded during gastrointestinal digestion, indicating that DMOLP-3 can be utilised by gut microorganisms. Furthermore, the prebiotic properties of MOLP and DMOLP-3 was studied using an in vitro faecal fermentation model. The results indicated that compared with MOLP, DMOLP-3 led to a decrease in both the colour and MW of the polysaccharides. In addition, this model exhibited enhanced solubility and antioxidant capabilities while also influencing the surface morphology. Moreover, DMOLP-3 can facilitate the proliferation of advantageous microorganisms and enhance the synthesis of short-chain fatty acids (SCFAs). These results provide valuable insights into the utilization of bioactive components in Moringa oleifera Lam. leaves for the intestinal health.
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Introduction: With the increasing demand for protein utilization, exploring new protein resources has become a research hotspot. Sacha Inchi Protein (SIP) is a high-quality plant protein extracted from Sacha Inchi meal. This study aimed to investigate the impact of SIP on mouse metabolomics and gut microbiota diversity and explore the underlying pathways responsible for its health benefits. Methods: In this study, the structural composition of SIP was investigated, and the effects of SIP on fecal metabolomics and intestinal microorganisms in mice were explored by LC-MS metabolomics technology analysis and 16S rRNA gene sequencing. Results: The results showed that SIP was rich in amino acids, with the highest Manuscript Click here to view linked References content of arginine, which accounted for 22.98% of the total amino acid content; the potential fecal metabolites of mice in the SIP group involved lipid metabolism, sphingolipid metabolism, arginine biosynthesis, and amino acid metabolism; SIP altered the microbial composition of the cecum in mice, decreased the Firmicutes/Bacteroidetes value, and It decreased the abundance of the harmful intestinal bacteria Actinobacteriota and Desulfobacterota, and increased the abundance of the beneficial intestinal bacteria Faecalibaculum, Dubosiella. Discussion: In conclusion, SIP is a high-quality plant protein with great potential for development in lipid-lowering, intestinal health, and mental illness, providing valuable clues for further research on its health-promoting mechanisms.
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OBJECTIVES: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD). METHOD: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed. RESULTS: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU. CONCLUSIONS: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded.