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Efficient and precise recovery of phenol from coal chemical wastewater (CCW) poses a significant challenge, prompting the development of a novel aldehyde-based, ester-based hyper-cross-linked polar resin (DES-COOC-CHO) in this study. Two distinct functional group modification methods were employed to enhance the screening effect of the resin. SEM, FT-IR, NMR, XPS, and BET characterizations confirmed the successful construction of the hyper-cross-linked polar resin, incorporation aldehyde and ester groups, exhibiting a special surface area of 627.2 m2/g and a microporous specific surface area percentage of 29.94%. DES-COOC-CHO adhered to the pseudo-second-order kinetic model and Langmuir model (maximum adsorption capacity of 118.0 mg/g). Its adsorption of phenol was spontaneous chemisorption, monolayer adsorption. Notably, even after undergoing 20 adsorption-desorption cycles, the resin maintained a stable adsorption capacity, showcasing excellent recoverability. In the presence of phenols sharing similar properties, DES-COOC-CHO exhibited superior selectivity for phenol. In real CCW, it achieved a remarkable 90% selective removal rate of phenol. The primary selective mechanism relied on the hydrogen bonding effect facilitated by aldehyde and ester groups, coupled with microporous sieving of appropriate size. In comparison with other adsorbent materials, DES-COOC-CHO exhibited superior adsorption properties, coupled with a cost-effective preparation process, presenting significant potential for practical applications.
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Fenol , Poluentes Químicos da Água , Águas Residuárias , Adsorção , Carvão Mineral , Espectroscopia de Infravermelho com Transformada de Fourier , Fenóis/química , Cinética , Poluentes Químicos da Água/química , Concentração de Íons de HidrogênioRESUMO
This study systematically analyzed the distribution characteristics, sources, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in Kuye River sediments, located in an energy and chemical industry base in northern Shaanxi, China. The results that revealed the concentrations of 16 PAHs in the sediment ranged from 1090.04 to 32,175.68 ngâg-1 dw, with the four-ring PAHs accounting for the highest proportion. Positive matrix factorization analysis (PMF) revealed the main sources of PAHs as incomplete fossil fuel combustion, biomass combustion, and traffic emissions. The total toxic equivalent concentration of BaP, risk quotient, and lifetime carcinogenic risk of PAHs suggested moderate to high contamination of PAHs in the area. The higher incremental lifetime carcinogenic risk (ILCR) indicated that PAH ingestion was the primary route of impact on public health, with children potentially being more susceptible to PAH exposure. This study can provide valuable theoretical support for implementing pollution prevention measures and ecological restoration strategies for rivers in energy and chemical industry areas.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Criança , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios , Indústria Química , Poluentes Químicos da Água/análise , Sedimentos Geológicos/análise , Monitoramento Ambiental/métodos , Medição de Risco , ChinaRESUMO
n-3 Polyunsaturated fatty acids (n-3 PUFA) has been widely used in foods, and pharmaceutical products due to its beneficial effects. The content of n-3 PUFA in natural oils is usually low, which decreases its added value. Thus, there is an increasing demand on the market for n-3 PUFA concentrates. This review firstly introduces the differences in bioavailability and oxidative stability between different types of PUFA concentrate (free fatty acid, ethyl ester and acylglycerol), and then provides a comprehensive discussion of different methods for enrichment of lipids with n-3 PUFA including physical-chemical methods and enzymatic methods. Lipases used for catalyzing esterification, transesterification and hydrolysis reactions play an important role in the production of highly enriched various types of n-3 PUFA concentrates. Lipase-catalyzed alcoholysis or hydrolysis reactions are the mostly employed method to prepare high-quality n-3 PUFA of structural acylglycerols. Although many important advantages offered by lipases in enrichment of n-3 PUFA, the high cost of enzyme limits its industrial-scale production. Further research should focus on looking for biological enzymes with extraordinary catalytic ability and clear selectivity. Other novel technologies such as protein engineering and immobilization may be needed to modify lipases to improve its selectivity, catalytic ability and reuse.
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Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Lipase/metabolismo , Hidrólise , Glicerídeos/químicaRESUMO
Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 µM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 µM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.
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Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Células Endoteliais/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Anticolesterolemiantes/química , Atorvastatina/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
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Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Granulócitos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Células Supressoras Mieloides/efeitos dos fármacos , Animais , Calgranulina B/fisiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/fisiologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/uso terapêutico , Granulócitos/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/patologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/efeitos dos fármacos , Microambiente TumoralRESUMO
RATIONALE: Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited. OBJECTIVE: In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice. METHODS AND RESULTS: We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice. CONCLUSIONS: Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
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Envelhecimento/patologia , Cardiopatias/terapia , Transplante de Células-Tronco/métodos , Animais , Células Cultivadas , Coração/crescimento & desenvolvimento , Coração/fisiopatologia , Cardiopatias/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/citologia , Miocárdio/metabolismo , Homeostase do Telômero , Função VentricularRESUMO
The nitrogen oxidation reaction (NOR) to form nitric acid by applying natural air and H2O under ambient conditions is a sustainable approach to achieving efficient and selective N2 fixation for industrial applications. In this study, four kinds of Co3O4 catalysts with a controllable microstructure were prepared to catalyze the direct NOR of N2 in the air. At the same time, the reaction mechanism of the conversion of N2 to nitric acid under catalytic ozonation was explored through experimental research and density functional theory (DFT) calculation. The results showed that the prepared porous nanosheets self-assembled into microflower-structured samples. The HCOF showed extraordinary catalytic performance for direct NOR to produce a high concentration of nitric acid. The maximum rate of nitric acid formation could be as high as 6.67 mmol/(h·gcat), which was higher than those of most reported photocatalytic or electrocatalytic N2 fixation processes for direct NOR to produce NO3-. Furthermore, the 15N isotopic-labeling experiment confirmed that the produced NO3- originated from N2 in the air by the direct NOR process. In the direct NOR mechanism, inert N2 molecules were captured at the Co3+ active sites by the acceptance-donation electron conduction mode, and the oxygen vacancies boosted the chemical adsorption of N2 molecules and greatly reduced the activation energy barrier of N2 molecules. The active free radicals â¢OH and â¢O2- generated by the decomposition of O3 molecules oxidized N2 to the intermediate *NO, which was the rate-determining step, and it was then absorbed by water to form nitric acid. The air catalytic ozonation method in this study was proposed as a facile pathway for efficient nitrogen fixation. This research provides a new method for environmental protection and efficient production of nitric acid at distributed sources.
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In response to the problem of high emulsified and dissolved oils being difficult to recovery from coal chemical wastewater (CCW), this study specifically constructed a non-polar, macropore, and hydrophobic adsorption material (pSt-X) based on the main components of these two oils (aromatics and phenols) for selective recovery. The results revealed that pSt-X had an adsorption capacity of 215.52 mg/g, which had remained stable for multiple recycling sessions, with an adsorption capacity constantly above 95 %. The pSt-X has significantly larger particle size (0.7 mm-1.2 mm), which simplifies the process of adsorption regeneration and effectively prevents the loss of the adsorbent powder problem. The pSt-X adsorbent demonstrated remarkable selectivity towards dissolved and emulsified oils, exhibiting removal rates of 90.2 % and 81.7 %, respectively. Moreover, pSt-X proved remarkable selectivity in removing aromatic hydrocarbons (AHs) and phenols, with impressive removal rates of 77.8 % and 85.9 %, respectively. The selective separation mechanism of pSt-X for oil substances was further analyzed, indicating that its selective adsorption of oils was primarily driven by hydrophobic, π-π, and hydrogen bonding interactions owing to its non-polar and macropore structure and hydrophobic properties. The results of this study provide solid theoretical support for green and low-carbon recovery of oil substances in CCW and are of positive practical importance for clean production in the coal chemical industry.
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Águas Residuárias , Poluentes Químicos da Água , Carvão Mineral , Adsorção , Óleos , Fenóis , Poluentes Químicos da Água/químicaRESUMO
Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization and difficulty in formation of cardiac chamber were yet to be overcome. We established a new method for robust generation of COs, via combination of methodologies of hiPSC-derived vascular spheres and directly differentiated cardiomyocytes from hiPSCs, and investigated the potential application of human COs in cardiac injury modelling and drug evaluation. The human COs we built displayed a vascularized and chamber-like structure, and hence were named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single-cell transcriptomics identified a total of six cell types in the vcCOs, including cardiomyocytes, cardiac precursor cells, endothelial cells, fibroblasts, etc. We successfully recaptured the processes of cardiac injury and fibrosis in vivo on vcCOs, and showed that the FDA-approved medication captopril significantly attenuated cardiac injury-induced fibrosis and functional disorders. In addition, the human vcCOs exhibited an obvious drug toxicity reaction to doxorubicin in a dose-dependent manner. We developed a three-step method for robust generation of chamber-like and vascularized complex vcCOs, and our data suggested that vcCOs might become a useful model for understanding pathophysiological mechanisms of cardiovascular diseases, developing intervention strategies and screening drugs.
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Doxorrubicina , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Organoides , Humanos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Doxorrubicina/farmacologia , Cardiopatias/patologia , Cardiopatias/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Captopril/farmacologia , Animais , Células Cultivadas , Avaliação de Medicamentos/métodosRESUMO
The complex composition of coal chemical wastewater (CCW), marked by numerous highly toxic aromatic compounds, induces the destabilization of the biochemical treatment system, leading to suboptimal treatment efficacy. In this study, a biochemical treatment system was established to efficiently degrade aromatic compounds by quantitatively regulating the dosage of co-metabolized substrates (specifically, the chemical oxygen demand (COD) Glucose: COD Sodium acetate = 3:1, 1:3, and 1:1). The findings demonstrated that the system achieved optimal performance under the condition that the ratio of COD Glucose to COD Sodium acetate was 3:1. When the co-metabolized substrate was added to the system at an optimal ratio, examination of pollutant removal and cumulative effects revealed that the removal efficiencies for COD and total organic carbon (TOC) reached 94.61 % and 86.40 %, respectively. The removal rates of benzene series, nitrogen heterocyclic compounds, polycyclic aromatic hydrocarbons, and phenols were 100 %, 100 %, 63.58 %, and 94.12 %, respectively. Research on the physiological response of microbial cells showed that, under optimal ratio regulation, co-metabolic substrates led to a substantial rise in microbial extracellular polymeric substances (EPS) secretion, particularly extracellular proteins. When the system reached the end of its operation, the contents of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) for proteins in the optimal group were 7.12 mg/g-SS and 152.28 mg/g-SS, respectively. Meanwhile, the ratio of α-Helix / (ß-Sheet + Random coil) and the proportion of intermolecular interaction forces were also increased in the optimal group. At system completion, the ratio of α-Helix / (ß-Sheet + Random coil) reached 0.717 (LB-EPS) and 0.618 (TB-EPS), respectively. Additionally, the proportion of intermolecular interaction forces reached 74.83 % (LB-EPS) and 55.03 % (TB-EPS). An in-depth analysis of the metabolic regulation of microorganisms indicated that the introduction of optimal ratios of co-metabolic substrates contributed to a noteworthy upregulation in the expression of Catechol 2,3-dioxygenase (C23O) and Dehydrogenase (DHA). The expression levels of C23O and DHA were measured at 0.029 U/mg Pro·g MLSS and 75.25 mg TF·(g MLSS·h)-1 (peak value), respectively. Correspondingly, enrichment of aromatic compound-degrading bacteria, including Thauera, Saccharimonadales, and Candidatus_Competibacter, occurred, along with the upregulation of associated functional genes such as Catechol 1,2-dioxygenase, Catechol 2,3-dioxygenase, Protocatechuate 3,4-dioxygenase, and Protocatechuate 4,5-dioxygenase. Considering the intricate system of multiple coexisting aromatic compounds in real CCW, this study not only obtained an optimal ratio for carbon source addition but also enhanced the efficient utilization of carbon sources and improved the capability of the system to effectively degrade aromatic compounds. Additionally, this paper established a theoretical foundation for metabolic regulation and harmless treatment within the biochemical treatment of intricate systems, exemplified by real CCW.
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Biodegradação Ambiental , Carbono , Carvão Mineral , Águas Residuárias , Águas Residuárias/química , Carbono/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/metabolismo , Análise da Demanda Biológica de Oxigênio , Hidrocarbonetos Policíclicos Aromáticos/metabolismoRESUMO
The application of molecularly imprinted material (MIM) is widely employed as a material for removing phenolic pollutants from the water environment, owing to its exceptional capacity for selective adsorption and high sensitivity. In this paper, the preparation principle, bonding types, and preparation methods of MIM have been comprehensively introduced. Meanwhile, according to the binding type of MIM with phenolic pollutants, three categories of hydroxyl bonding, hydroxyl carboxyl bonding, and hydroxyl nitro bonding were carried out to explain its application to phenolic pollutants. Strategies for addressing the challenges of selective instability, high regeneration costs, and template leakage in MIM applications were summarized. These strategies encompassed the introduction of superior carriers, enhancements in preparation processes, and the utilization of molecular dynamics simulation-assisted technology. Finally, the prospects in the three aspects of material preparation, process coupling, and recycling. In summary, this paper has demonstrated the potential of utilizing MIM for the selective treatment of phenolic pollutants from the water environment.
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Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of â¼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.
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Digital light processing (DLP) bioprinting, known for its high resolution and speed, enables the precise spatial arrangement of biomaterials and has become integral to advancing tissue engineering and regenerative medicine. Nevertheless, inherent light scattering presents significant challenges to the fidelity of the manufactured structures. Herein, we introduce a photoinhibition strategy based on Rutin nanoparticles (Rnps), attenuating the scattering effect through concurrent photoabsorption and free radical reaction. Compared to the widely utilized biocompatible photoabsorber tartrazine (Tar), Rnps-infused bioink enhanced printing speed (1.9×), interlayer homogeneity (58% less overexposure), resolution (38.3% improvement), and print tolerance (3× high-precision range) to minimize trial-and-error. The biocompatible and antioxidative Rnps significantly improved cytocompatibility and exhibited resistance to oxidative stress-induced damage in printed constructs, as demonstrated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). The related properties of Rnps facilitate the facile fabrication of multimaterial, heterogeneous, and cell-laden biomimetic constructs with intricate structures. The developed photoinhibitor, with its profound adaptability, promises wide biomedical applications tailored to specific biological requirements.
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BACKGROUND: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. METHODS: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation-qPCR (MeRIP-qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. RESULTS: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. CONCLUSION: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.
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Biomarcadores Tumorais , Células Neoplásicas Circulantes , Neoplasias Gástricas , Vimentina , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Vimentina/metabolismoRESUMO
In this study, enzymatic two-step hydrolysis of tuna oil was performed to release saturated (SFAs) and monounsaturated fatty acids (MUFAs) from triacylglycerols (TAGs) to obtain acylglycerols rich in ω-3 polyunsaturated fatty acids (PUFAs). At the first step, AY "Amano" 400SD was chosen to mainly hydrolyze MUFAs from tuna oil under the conditions as described previously. At the second step, second hydrolysis by Candida antarctica lipase A (CAL-A) was conducted to mainly remove SFAs in acylglycerols isolated from the hydrolysate obtained at the first step. The second hydrolysis conditions were optimized. Under the optimum conditions, the content of ω-3 PUFAs in acylglycerols increased from initial 34.3% in tuna oil to 57.65% after initial hydrolysis and further to 68.94% after second hydrolysis. The most important finding in this study is that AY "Amano" 400SD and CAL-A selectively hydrolyze MUFAs and SFAs, respectively, which may have the potential application for PUFAs concentration.
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Ácidos Graxos Ômega-3 , Lipase , Animais , Catálise , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados , Glicerídeos , Hidrólise , Triglicerídeos , AtumRESUMO
Objective: To evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC). Materials and methods: This was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test. Results: From January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p<0.05). In multivariate analysis, downstaging N was an independent prognostic factor for OS. Meanwhile, downstaging T and downstaging N remained independent prognostic factors for PFS. Conclusions: Although the consistency between mrTRG and pTRG is only fair, favorable mrTRG after neo-CRT may be used as a potential prognostic factor for LARC patients.
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Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.
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Macrófagos , Músculo Esquelético , Camundongos , Animais , Camundongos Knockout , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Macrófagos/metabolismo , Modelos Animais de Doenças , Isquemia , Membro Posterior/irrigação sanguínea , Neovascularização Fisiológica , Proteínas de Transporte/metabolismoRESUMO
Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.