RESUMEN
Objective: We aimed to investigate the immunological significance of M2 macrophage-related genes in lung cancer (LC) patients, specifically focusing on constructing a risk score to predict patient prognosis and response to immunotherapy. Methods: We developed a novel risk score by identifying and incorporating 12 M2 macrophage-related genes. The risk score was calculated by multiplying the expression levels of risk genes by their respective coefficients. Through comprehensive enrichment analysis, we explored the potential functions distinguishing high- and low-risk groups. Moreover, we examined the relationship between patients in different risk groups and immune infiltration as well as their response to immunotherapy. The single-cell RNA sequencing data were acquired to ascertain the spatial pattern of RNF130 expression. The expression of RNF130 was examined using TCGA datasets and verified by HPA. The qRT-PCR was employed to examine RNF130 expression in LC cells. Finally, in vitro experiments were carried out to validate the expression and function of RNF130. Results: Our results indicated that the risk score constructed from 12 M2 macrophage-related genes was an independent prognostic factor. Patients in the high-risk group had a significantly worse prognosis compared to those in the low-risk group. Functional enrichment analysis showed a significant relationship between the risk score and immunity. Furthermore, we explored immune infiltration in different risk groups using seven immune algorithms. The results demonstrated a negative correlation between high-risk group patients and immune infiltration of B cells, CD4+ cells, and CD8+ cells. We further validated these findings using an immunotherapy response database, which revealed that high-risk patients were more likely to exhibit immune evasion and might have poorer immunotherapy outcomes. Additionally, drug sensitivity analysis indicated that patients in the high-risk group were more sensitive to certain chemotherapeutic and targeted drugs than those in the low-risk group. Single-cell analysis indicated that macrophages were the primary site of RNF130 distribution. The results from the TCGA and HPA database demonstrated a trend toward a low expression of RNF130 in LC. Finally, in vitro experiments further validated the expression and function of RNF130 in LC cells. Conclusions: The high-risk group constructed with M2 macrophage-related genes in LC was closely associated with poor prognosis, low immune cell infiltration, and poorer response to immunotherapy. This risk score can help differentiate and predict the prognosis and immune status of LC patients, thereby aiding in the development of precise and personalized immunotherapy strategies.
RESUMEN
The presence of fluoride ions (F-) in photovoltaic (PV) wastewater significantly affects the integrity of the ecological environment. In contrast to direct current electrocoagulation (DC-EC), positive single-pulse electrocoagulation (PSPC-EC) shows a significant reduction in both the formation of passivation films on electrodes and the consumption of electrical energy. Under the experimental conditions of an Al-Al-Al-Al electrode combination, an electrode spacing of 1.0 cm, a NaCl concentration of 0.05 mol L-1, an initial pH of 5.6, an initial F- concentration of 5 mg L-1, a current density of 5 A m-2, a pulse frequency of 500 Hz, and a 40 % duty cycle, the achieved equilibrium F- removal efficiencies were 84.0 % for DC-EC and 88.0 % for PSPC-EC, respectively, accompanied by power consumption of 0.0198 kWh·mg-1 and 0.0073 kWh·mg-1. The flocs produced in the PSPC-EC process were characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy and it is revealed that the F- removal mechanisms in the PSPC-EC process include co-precipitation, hydrogen bond complexation, and ion exchange. When the actual PV wastewater was finally subjected to treatment under the optimal PSPC-EC conditions, the F- concentration in the wastewater was reduced from 4.6 mg L-1 to 1.4 mg L-1. This paper provides both a theoretical framework and a technological basis for the application of PSPC-EC in the advanced treatment of PV wastewater.
Asunto(s)
Fluoruros , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Fluoruros/química , Contaminantes Químicos del Agua/química , Electrodos , Eliminación de Residuos Líquidos/métodos , Electrocoagulación/métodosRESUMEN
The performance of catalytic ability of MFe2O4/MoS2 in the ozonation process was investigated in this work. The synthesized MnFe2O4/MoS2 was optimize prepared and then characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photo-electron spectroscopy, and magnetic saturation strength. The results showed that when Cphenol = 200 mg/L, initial pH = 9.0, Q = 0.10 L/min, and CMnFe2O4/MoS2 = 0.10 g/L, MnFe2O4/MoS2 addition improved the degradation efficiency of phenol by 20.0%. The effects of pH, catalyst dosage, and inorganic ions on the phenol removal by the MnFe2O4/MoS2 catalytic ozonation were investigated. Five cycle experiments proved that MnFe2O4/MoS2 had good recyclability and stability. MnFe2O4/MoS2 also showed good catalytic performance in the treatment of coal chemical wastewater pesticide wastewater. The MnFe2O4 doped with MoS2 could provide abundant surface active sites for ozone and promote the stable cycle of Mn2+/Mn3+and Fe2+/Fe3+, thus generating large amounts of â¢OH and improving the degradation of phenol by ozonation. The MnFe2O4/MoS2/ozonation treatment system provides a technical reference and theoretical basis for industrial wastewater treatment.
Asunto(s)
Ozono , Aguas Residuales , Aguas Residuales/química , Ozono/química , Catálisis , Compuestos Férricos/química , Compuestos de Manganeso/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Fenoles/química , Molibdeno/química , Disulfuros/químicaRESUMEN
Green hydrogen from electrolysis of water has attracted widespread attention as a renewable power source. Among several hydrogen production methods, it has become the most promising technology. However, there is no large-scale renewable hydrogen production system currently that can compete with conventional fossil fuel hydrogen production. Renewable energy electrocatalytic water splitting is an ideal production technology with environmental cleanliness protection and good hydrogen purity, which meet the requirements of future development. This review summarizes and introduces the current status of hydrogen production by water splitting from three aspects: electricity, catalyst and electrolyte. In particular, the present situation and the latest progress of the key sources of power, catalytic materials and electrolyzers for electrocatalytic water splitting are introduced. Finally, the problems of hydrogen generation from electrolytic water splitting and directions of next-generation green hydrogen in the future are discussed and outlooked. It is expected that this review will have an important impact on the field of hydrogen production from water.
RESUMEN
BACKGROUND AND OBJECTIVE: The current study aimed to explore the factors influencing early progression (EP) and late progression (LP) in locally advanced rectal cancer (LARC) patients. METHODS: The patients were classified into EP and LP groups using one year as a cutoff. The random survival forest model was utilized to calculate the probability of time-to-progression. Besides, inverse probability of treatment weighting (IPTW) analysis and the Surveillance, Epidemiology, and End Results (SEER) were conducted to validate our results. RESULTS: Our study revealed that PNI, CEA level, and pathological stage were independent prognostic factors for PFS both in EP group and LP group. For EP group patients, Group 1 had the highest probability of progression at the 9th month of follow-up, while Group 2 exhibited the highest probability at the 6th month. Group 3, on the other hand, showed two peaks of progression at the 4th and 8th months of follow-up. As for LP group patients, Groups 4, 5, and 6 all exhibited peaks of progression between the 18th and 24th months of follow-up. Furthermore, our results suggested that PNI was also an independent prognostic factor affecting OS in both EP group and LP group. Finally, the analysis of IPTW and SEER database further confirmed our findings. CONCLUSIONS: Our results indicated a significant correlation between immune and nutritional status with PFS and OS in both EP and LP groups. These insights can aid healthcare professionals in effectively identifying and evaluating patients' nutritional status, enabling them to develop tailored nutrition plans and interventions.
Asunto(s)
Progresión de la Enfermedad , Neoplasias del Recto , Programa de VERF , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , Factores de Riesgo , Adulto , Estadificación de Neoplasias , Factores de Tiempo , Estudios de SeguimientoRESUMEN
The photoelectric characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) films significantly affect the power conversion efficiency and stability of Si/PEDOT:PSS hybrid solar cells. In this paper, we investigated PEDOT:PSS modification with alcohol ether solvents (dipropylene glycol methyl ether (DPM) and propylene glycol phenyl ether (PPH)). The reduction of PSS content and the transformation of the PEDOT chain from benzene to a quinone structure in PEDOT:PSS induced by doping with DPM or PPH are the reasons for the improved conductivity of PEDOT:PSS films. DPM and PPH doping improves the quality of silicon with the PEDOT:PSS heterojunction and silicon surface passivation, thereby reducing the surface recombination of charge carriers, which improves the photovoltaic performance of Si/PEDOT:PSS solar cells. Comparing the power conversion performance (PCE) and air stability of Si/PEDOT:PSS solar cells with DPM (13.24%), DPH (13.51%), ethylene glycol (EG, 13.07%), and dimethyl sulfoxide (DMSO, 12.62%), it is suggested that doping with DPM and DPH can replace DMSO and EG to enhance the performance of Si/PEDOT:PSS solar cells. The EG and DMSO solvents not only have a certain toxicity to the human body but also are not environmentally friendly. In comparison to DMSO and EG, DPM and DPH are more economical and environmentally friendly, helping to reduce the manufacturing cost of Si/PEDOT:PSS solar cells and making them more conducive to their commercial applications.
RESUMEN
Objective: MRPS24 (Mitochondrial Ribosomal Protein S24) belongs to the mitochondrial ribosomal protein family, which participates in the protein synthesis of the mitochondrion. However, the relationship of MRPS24 with lung adenocarcinoma (LUAD) remained unknown. We aimed to identify its immunological and functional mechanisms in LUAD. Methods: The analysis of MRPS24 expression, clinical features, diagnosis, prognosis, function analysis, genetic alteration, copy number variations, methylation, and tumor microenvironment was investigated by the TCGA, UCSC Xena, GEO, HPA, GEPIA, cBioPortal, MethSurv, TIMER, TIMER2.0, and TISIDB databases. Results: MRPS24 was found to be more abundant in LUAD tumor tissue than in normal tissue. High levels of MRPS24 expression were found to be an independent prognostic factor by multivariate analysis. Functional analysis revealed that MRPS24 expression was associated with the immune, cell cycle and methylation. MRPS24 methylation level was inversely linked with its expression (p < 0.001). Patients with low MRPS24 methylation had a worse prognosis than those with high methylation (p < 0.05). In addition, the result revealed that the MRPS24 expression was inversely linked to the immune cell infiltration in LUAD. Finally, the validations of the expression level, prognosis, and immune cell infiltration of MRPS24 were in accordance with our previous results. Conclusions: This study systematically explored that MRPS24 expression was significantly correlated with prognosis, tumorigenesis, genetic alteration, copy number variations, methylation, and immune cell infiltration in LUAD. MRPS24 might be a potential immune-related biomarker in the development and treatment of LUAD, thereby acting as a promising predictor of immunotherapy response in LUAD.
Asunto(s)
Proteínas de Unión al ADN , Leiomiosarcoma , Neoplasias Uterinas , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/genética , Femenino , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/diagnóstico , Proteínas de Unión al ADN/genética , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genéticaRESUMEN
HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted spring viremia of carp virus (SVCV) and cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.
Asunto(s)
Enfermedades de los Peces , Proteínas de Peces , Proteínas Serina-Treonina Quinasas , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/metabolismo , Rhabdoviridae/fisiología , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinaria , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/inmunología , Inmunidad Innata/genética , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/inmunología , Carpas/inmunología , Carpas/genética , Herpesviridae/fisiología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/inmunología , Interferón Tipo I/inmunología , Interferón Tipo I/genética , Interferón Tipo I/metabolismo , Proteínas de Pez CebraRESUMEN
The effects of adipocyterich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyterich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARMassociated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro. Specifically, the peroxisome proliferatoractivated receptor γ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARMeducated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.
Asunto(s)
Anilidas , Neoplasias Ováricas , Animales , Femenino , Humanos , Ratones , Adipocitos/metabolismo , Apoptosis , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Ratones Endogámicos C57BL , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Microambiente Tumoral , Regulación hacia ArribaRESUMEN
Food provided a material foundation for the development of human society and was an important cornerstone for ensuring national security. The Chinese government has always attached great importance to food security, which is not only related to economic development and social stability but also to national security and self-reliance. As the core region for grain production and the supply of staple food in China, the major grain-producing areas account for 78.25% of the total national grain output, truly earning the title of China's "granary". Considering the establishment of 13 major grain-producing regions across the country in 2004 as a quasi-natural experiment, the impact of policies in major grain-producing regions on ensuring national food security is examined using a difference-in-differences method based on inter-provincial panel data for 30 provinces across the country from 1997 to 2020, and the mechanisms of their effects are further analyzed. The findings show that (1) the main producing-areas policy has a significant driving effect on China's food security, with an average annual increase of 0.0351 units in the food-security index, and the impact is expanding year by year. (2) The policy of the main grain-producing provinces mainly plays a role in guaranteeing food security by expanding the scale of grain cultivation and the scale of family land management in the main grain-producing provinces, and the scale effect of grain cultivation has a more significant impact. Further adjusting and improving the policy of the main grain-producing areas and expanding the scale-driven effect of this policy are of great significance for transforming agricultural production methods and realizing a strong agricultural country.
RESUMEN
Clinically, histopathology images always offer a golden standard for disease diagnosis. With the development of artificial intelligence, digital histopathology significantly improves the efficiency of diagnosis. Nevertheless, noisy labels are inevitable in histopathology images, which lead to poor algorithm efficiency. Curriculum learning is one of the typical methods to solve such problems. However, existing curriculum learning methods either fail to measure the training priority between difficult samples and noisy ones or need an extra clean dataset to establish a valid curriculum scheme. Therefore, a new curriculum learning paradigm is designed based on a proposed ranking function, which is named The Ranking Margins (TRM). The ranking function measures the 'distances' between samples and decision boundaries, which helps distinguish difficult samples and noisy ones. The proposed method includes three stages: the warm-up stage, the main training stage and the fine-tuning stage. In the warm-up stage, the margin of each sample is obtained through the ranking function. In the main training stage, samples are progressively fed into the networks for training, starting from those with larger margins to those with smaller ones. Label correction is also performed in this stage. In the fine-tuning stage, the networks are retrained on the samples with corrected labels. In addition, we provide theoretical analysis to guarantee the feasibility of TRM. The experiments on two representative histopathologies image datasets show that the proposed method achieves substantial improvements over the latest Label Noise Learning (LNL) methods.
Asunto(s)
Algoritmos , Interpretación de Imagen Asistida por Computador , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Histocitoquímica/métodos , Técnicas Histológicas/métodosRESUMEN
We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.
Asunto(s)
Neoplasias Hepáticas , Neoplasias del Recto , Humanos , Estudios de Seguimiento , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Recto/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , PronósticoRESUMEN
The challenging international landscape and exacerbated extreme weather conditions contribute to the instability of global grain trade, complicating its impact on food security. This complexity is particularly pronounced for varieties like rice, which are heavily affected by policy-driven trade restrictions. There is insufficient research on how a country's rice trade characteristics affect food security. A network analysis approach is adopted to intricately dissect the structural characteristics of rice trade. To explore causality with food insecurity, this paper chooses structural holes and centrality as representatives of trade network characteristics and regresses them on the food insecurity indicator. With cross-national data spanning over 30 years, the network analysis provides a clear portrayal of the dynamic changes in international rice trade. The overall resilience of the trade network has increased, but specific countries' vulnerability has also risen. Unlike the changing trends in features observed in grain and food trade networks, there is a notable intensification in the imbalance of power distribution in the rice trade network compared to over 30 years ago. The panel data regression results show that constraint, indicating the scarcity of structural holes or connections to stronger trading partners, significantly and positively influences a country's level of food insecurity. Based on these findings, the policy proposal for importing countries emphasizes creating strategic trade connections. By choosing appropriate trade partners that reduce constraint, food security can be enhanced, even without improvements in other conditions.
RESUMEN
Microbial contamination poses a serious threat to human life and health. Through the intersection of material science and modern medicine, advanced bionic hydrogels have shown great potential for biomedical applications due to their unique bioactivity and ability to mimic the extracellular matrix environment. In particular, as a promising antimicrobial material, the synthesis and practical biomedical applications of peptide-based antimicrobial hydrogels have drawn increasing research interest. The synergistic effect of peptides and hydrogels facilitate the controlled release of antimicrobial agents and mitigation of their biotoxicity while achieving antimicrobial effects and protecting the active agents from degradation. This review reports on the progress and trends of researches in the last five years and provides a brief outlook, aiming to provide theoretical background on peptide-based antimicrobial hydrogels and make suggestions for future related work.
Asunto(s)
Antiinfecciosos , Hidrogeles , Humanos , Hidrogeles/farmacología , Materiales Biocompatibles/farmacología , Péptidos/farmacología , Antiinfecciosos/farmacologíaRESUMEN
As a typical type of organic flocculant, chitosan is limited by its poor water solubility and narrow pH range application. Grafting modification can improve chitosan's solubility and availability through linking macromolecular chains with other types of water-soluble groups or functional side groups. In this study, dielectric barrier discharge (DBD) was used to active the surface of chitosan, then activated chitosan was polymerized with acrylamide to synthesize a chitosan-based flocculant, chitosan-acrylamide (CS-AM). During the synthesis of CS-AM, the optimal conditions were determined as follows: discharge time of 5 min, discharge power of 60 W, total monomer mass concentration of 80 g L-1, polymerization time of 3 h, polymerization temperature of 70 °C, and m(CS) : m(AM) ratio of 1 : 3. The structure and morphological characteristics of CS-AM were investigated and analyzed by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric (TG) analysis, scanning electron microscopy (SEM), X-ray diffraction (XRD) and N2 physical adsorption, respectively. The removal efficiency of kaolin suspension and CNTs suspension can reach up to 95.9% and 90.2% after flocculation of CS-AM. Furthermore, the zeta potential of the supernatant from the CS-AM treated kaolin suspension at different pH values was examined, and the flocculation mechanism of CS-AM was analyzed. This study provides new ideas for the preparation and development of modified chitosan and broadens its application in water treatment.
RESUMEN
BACKGROUND: The plant Ainsliaea fragrans Champ. (A. fragrans) named "Xingxiang Tuerfeng", is a traditional herb with a long history of therapeutic practice in southern China in the treatment of gynecological diseases. PURPOSE: The anti-inflammatory extract of Ainsliaea fragrans Champ. (AF-ext) exhibited anti-primary dysmenorrhea (PD) activity in oxytocin-induced mice. This study aimed to unravel the underlying mechanisms of AF-ext on PD by the integrative approach of network pharmacology and experimental verification. METHODS: First, the therapeutic targets of AF-ext are predicted using network pharmacology and molecular docking methods. Second, activity screening and immunoblotting methods were used for target validation. Then, the therapeutic effect of AF-ext on PD was evaluated using oxytocin-induced mice and uterine strips model. RESULTS: AF-p1, and AF-p2, the active ingredients of AF-ext, showed inhibitory effects on COX1/2 and EGFR, and all five active components showed antagonistic activity on TRPV1. AF-ext (25, 50, 100 mg/kg) could significantly reduce the number of writhing times and prolong writhing latencies in a dose-dependent manner. AF-ext inhibited spasmolytic activity in uterine strips induced by oxytocin and Ca2+ stimulation. AF-ext inhibited NF-κB/COX-2/PG pathway and activation of the NLRP3 inflammasome in PD mice. It significantly downregulated the PD-induced overexpression of p-p65/p65, p-IκBα, and COX-2 by inhibiting the NF-κB pathway. Moreover, the overexpression of NLRP3, p20/pro-Caspase 1, and p17/pro-IL-1ß was greatly downregulated. CONCLUSIONS: AF-ext demonstrated anti-inflammatory, analgesic, and spasmolytic activity in the treatment of PD. It inhibited the NF-κB/COX-2/PG pathway and NLRP3 inflammasome activation in PD mice with a multi-target approach.
Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Femenino , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Oxitocina/farmacología , Dismenorrea/tratamiento farmacológico , Farmacología en Red , Parasimpatolíticos , Ciclooxigenasa 2 , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacologíaRESUMEN
BACKGROUND: Bone fracture is a common orthopedic disease that needs over 3 months to recover. Promoting the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is beneficial for fracture healing. Therefore, this research aimed to study the roles of long non-coding RNA (lncRNA) KCNQ10T1 in osteogenic differentiation of BMSCs. METHODS: BMSCs were treated with osteogenic medium and assessed by CCK-8 and flow cytometry assays. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), as well as concentration of osteoblast markers were measured to evaluate osteogenic differentiation of BMSCs. Western blot was employed to detect proteins; while, qRT-PCR was for mRNA levels. Additionally, targeted relationships between KCNQ10T1 and miR-19a-3p, as well as miR-19a-3p and SMAD5 were verified by dual luciferase reporter gene assay along with RNA pull-down method. RESULTS: Upregulation of KCNQ10T1 promoted the ALP staining and ARS intensity, increased the cell viability and decreased the apoptosis rate of BMSCs. Besides, KCNQ10T1 overexpression increased the ALP, OPG, OCN and OPN protein levels. KCNQ10T1 sponges miR-19a-3p, which targets Smad5. Upregulated miR-19a-3p reversed the overexpressed KCNQ10T1-induced effects, and depletion of SMAD5 reversed the miR-19a-3p inhibitor-induced effects on osteogenic medium-treated BMSCs. CONCLUSIONS: Upregulation of KCNQ10T1 promoted osteogenic differentiation of BMSCs through miR-19a-3p/SMAD5 axis in bone fracture.
Asunto(s)
Fracturas Óseas , Células Madre Mesenquimatosas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Diferenciación Celular/genética , Células Cultivadas , Fracturas Óseas/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Lysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Pronóstico , Genes Reguladores , Lisosomas/genética , Factores de Transcripción , Microambiente Tumoral/genética , Glicoproteínas de Membrana , Chaperonas Moleculares , Proteínas de la Membrana , Proteínas OncogénicasRESUMEN
The aim of this study was to investigate a more practical method for obtaining non-extractable polyphenols (NEPPs) from blue honeysuckle fruit pomace. Three methods, namely acid, alkaline, and enzymatic hydrolysis, were utilized to extract NEPPs. The findings indicated that alkaline hydrolysis was the most effective method for releasing NEPPs, which demonstrated higher levels of total flavonoid content (TFC) and total phenolic content (TPC) from blue honeysuckle fruit pomace. Additionally, higher TPC and TFC levels were related to a stronger antioxidant capacity. Qualitative and quantitative analysis using HPLC-HR-TOF-MS/MS revealed that acid hydrolysis resulted in a greater concentration of certain phenolic acids, while alkaline hydrolysis yielded a higher concentration of flavonoids, and enzymatic hydrolysis produced a wider range of phenolic compositions. Despite the fact that enzymatic hydrolysis is considered a gentler method, the researchers concluded that alkaline hydrolysis was the most appropriate method for obtaining NEPPs from blue honeysuckle fruit pomace.