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1.
Water Environ Res ; 96(7): e11080, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38970489

RESUMEN

The presence of perfluoroalkyl substances (PFAS) in the environment poses a significant threat to ecological safety and environmental health. Widespread microplastics (MPs) have been recognized as vectors for emerging contaminants due to human activities. However, the adsorption behaviors of PFAS on MPs, especially on aged MPs, have not been extensively investigated. This study aimed to investigate the adsorption behaviors of perfluorooctanoic acid (PFOA) on aged MPs (polystyrene, polyethylene, and polyethylene terephthalate) treated with UV irradiation and persulfate oxidation under salinity and dissolve organic matter (DOM) condition. Carbonyl index values of MPs increased after the aged treatment, indicating the production of oxygen-containing groups. The PFOA adsorption on aged MPs was impacted by the co-existence of Na+ ions and DOM. As PFOA adsorption onto aged MPs was mainly controlled by hydrophobic interaction, the electrostatic interaction also made a contribution, but there was no significant change in PFOA adsorption behavior between the pristine and aged MPs. While these findings provide insight into PFAS adsorption on aged MPs, further research is necessary to account for the complexity of the real environment. PRACTITIONER POINTS: Adsorption behaviors of perfluorooctanoic acid (PFOA) on aged microplastics were investigated. Hydrophobic interaction mainly controlled PFOA adsorption on aged microplastics (MPs). Co-existence dissolve organic matter and salinity influenced PFOA adsorption behaviors on aged MPs.


Asunto(s)
Caprilatos , Fluorocarburos , Microplásticos , Contaminantes Químicos del Agua , Fluorocarburos/química , Caprilatos/química , Microplásticos/química , Adsorción , Contaminantes Químicos del Agua/química
3.
RSC Adv ; 14(30): 21342-21354, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38979462

RESUMEN

Presently, there are several issues associated with solid waste fly ash, such as its accumulation and storage, low comprehensive utilization rate, lack of high-value utilization technology, environmental risk and ecological impact. Thus, based on the high silica content and adsorption characteristics of fly ash, two novel adsorbents, namely mesoporous silica-based material (MSM) and sodium dodecyl sulfate-modified fly ash (SDS-FA), were prepared using an ultrasound-assisted alkali fusion-hydrothermal method and surface modification method. Furthermore, effects of adsorbent dosage, initial pH, contact time, and initial concentration of the solution on the adsorption of the organic pollutant methylene blue (MB) by fly ash, MSM, and SDS-FA were investigated to select the optimal modified high silica fly ash adsorbent. Based on the adsorption isotherms and adsorption kinetics, together with SEM, XRD, FTIR and BET analyses, the adsorption mechanism of MSM for MB was revealed. The results showed that under the conditions of an adsorbent dosage of 2 g L-1, initial pH of 9, contact time of 150 min, and initial concentration of 100 mg L-1, MSM and SDS-FA exhibited removal efficiencies of 92.69% and 84.64% for MB, respectively, which were significantly higher than that of fly ash alone. The adsorption of MB by MSM and SDS-FA followed the Langmuir model and pseudo-second-order kinetics, indicating monolayer adsorption with chemical adsorption as the dominant mechanism. The mechanism of the adsorption of MB by MSM is mainly the result of the synergistic effect among its increased specific surface area, hydrogen bonding, ion exchange, and electrostatic interactions. After five cycles of adsorption-desorption process, the removal efficiency of MSM for MB consistently remained above 80%. Therefore, MSM can serve as a valuable reference for the resource utilization of fly ash and remediation of dye-polluted wastewater.

4.
Bioresour Technol ; : 130947, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897548

RESUMEN

Intermittent hydroxylamine (NH2OH) dosing strategy was applied to enhance the stability of partial nitrification and total nitrogen (N) removal efficiency (TNRE) in a continuous-flow process. The results showed 2 mg/L of NH2OH dosing (once every 6 h) could maintain stably partial nitrification with nitrite accumulation rate (NAR) of 91.6 % and TNRE of 92.6 %. The typical cycle suggested NH2OH dosing could promote simultaneous nitrification-denitrification (SND) and endogenous denitrification (END) while inhibit exogenous denitrification (EXD). Nitrification characteristics indicated the NH2OH dosing enhanced stability of partial nitrification by suppressing specific nitrite oxidation rate (SNOR), Nitrospira and nitrite oxidoreductase enzyme (Nxr). The microbial community suggested the aerobic denitrfiers, denitrifying glycogen accumulating organisms (DGAOs) and traditional denitrfiers were the potential contributor for advanced N removal. Moreover, NH2OH dosage was positively associated with NAR, SND and END. Overall, this study offers a feasible strategy to maintain sustainably partial nitrification that has great application potential.

5.
Int J Biol Sci ; 20(7): 2640-2657, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725843

RESUMEN

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteína HMGA1a , Inhibidores mTOR , Proteína Proto-Oncogénica c-ets-1 , Proteína 1A de Unión a Tacrolimus , Animales , Humanos , Ratones , Línea Celular Tumoral , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Proteína HMGA1a/metabolismo , Proteína HMGA1a/genética , Ratones Desnudos , Inhibidores mTOR/farmacología , Inhibidores mTOR/uso terapéutico , Proteína Proto-Oncogénica c-ets-1/metabolismo , Proteína Proto-Oncogénica c-ets-1/genética , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Sirolimus/uso terapéutico , Proteína 1A de Unión a Tacrolimus/metabolismo , Proteína 1A de Unión a Tacrolimus/genética , Serina-Treonina Quinasas TOR/metabolismo
6.
Molecules ; 29(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38792045

RESUMEN

Efficient and thorough treatment of dye wastewater is essential to achieve ecological harmony. In this study, a new type of calcium-based modified coal gangue (Ca-CG) was prepared by using solid waste coal gangue as raw material and a CaCl2 modifier, which was used for the removal of malachite green, methylene blue, crystal violet, methyl violet and other dyes in water. When the dosage of Ca-CG was 1-5 g/L, the dosage of Ca-CG was the main factor affecting the dye adsorption effect. The adsorption effects of Ca-CG on four dyes were as follows: malachite green > crystal violet > methylene blue > methyl violet. Kinetics, isotherms and thermodynamic analysis showed that the adsorption of malachite green, methyl blue, crystal violet and methyl violet by Ca-CG fitted the second-order kinetic model, and adsorption with chemical reaction is the main process. The adsorption of four dyes by Ca-CG conformed to the Freundlich model, which is dominated by multi-molecular layer adsorption, and the adsorption was easy to carry out. The adsorption process of Ca-CG on the four dyes was spontaneous. The results of FTIR, XRD and SEM showed that the calcium-based materials such as lipscombite and dolomite were the key to the adsorption of malachite green by Ca-CG, and the main mechanisms for the adsorption of malachite green by Ca-CG are surface precipitation, electrostatic action, and chelation reaction. Ca-CG adsorption has great potential for the removal of dye wastewater.

7.
Cell Death Dis ; 15(5): 349, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769167

RESUMEN

Osteosarcoma is a malignant bone tumor that primarily inflicts the youth. It often metastasizes to the lungs after chemotherapy failure, which eventually shortens patients' lives. Thus, there is a dire clinical need to develop a novel therapy to tackle osteosarcoma metastasis. Methionine dependence is a special metabolic characteristic of most malignant tumor cells that may offer a target pathway for such therapy. Herein, we demonstrated that methionine deficiency restricted the growth and metastasis of cultured human osteosarcoma cells. A genetically engineered Salmonella, SGN1, capable of overexpressing an L-methioninase and hydrolyzing methionine led to significant reduction of methionine and S-adenosyl-methionine (SAM) specifically in tumor tissues, drastically restricted the growth and metastasis in subcutaneous xenograft, orthotopic, and tail vein-injected metastatic models, and prolonged the survival of the model animals. SGN1 also sharply suppressed the growth of patient-derived organoid and xenograft. Methionine restriction in the osteosarcoma cells initiated severe mitochondrial dysfunction, as evident in the dysregulated gene expression of respiratory chains, increased mitochondrial ROS generation, reduced ATP production, decreased basal and maximum respiration, and damaged mitochondrial membrane potential. Transcriptomic and molecular analysis revealed the reduction of C1orf112 expression as a primary mechanism underlies methionine deprivation-initiated suppression on the growth and metastasis as well as mitochondrial functions. Collectively, our findings unraveled a molecular linkage between methionine restriction, mitochondrial function, and osteosarcoma growth and metastasis. A pharmacological agent, such as SGN1, that can achieve tumor specific deprivation of methionine may represent a promising modality against the metastasis of osteosarcoma and potentially other types of sarcomas as well.


Asunto(s)
Neoplasias Óseas , Metionina , Mitocondrias , Osteosarcoma , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/genética , Osteosarcoma/tratamiento farmacológico , Metionina/deficiencia , Metionina/metabolismo , Humanos , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Línea Celular Tumoral , Ratones , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Metástasis de la Neoplasia , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/farmacología , Ratones Desnudos , Especies Reactivas de Oxígeno/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
8.
Sci Rep ; 14(1): 9927, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688999

RESUMEN

Aiming at the acid mine drainage (AMD) in zinc, copper and other heavy metals treatment difficulties, severe pollution of soil and water environment and other problems. Through the ultrasonic precipitation method, this study prepared fly ash-loaded nano-FeS composites (nFeS-F). The effects of nFeS-F dosage, pH, stirring rate, reaction time and initial concentration of the solution on the adsorption of Zn(II) and Cu(II) were investigated. The data were fitted by Lagergren first and second-order kinetic equations, Internal diffusion equation, Langmuir and Freundlich isotherm models, and combined with SEM, TEM, FTIR, TGA, and XPS assays to reveal the mechanism of nFeS-F adsorption of Zn(II) and Cu(II). The results demonstrated that: The removal of Zn(II) and Cu(II) by nFeS-F could reach 83.36% and 70.40%, respectively (The dosage was 8 g/L, pH was 4, time was 150 min, and concentration was 100 mg/L). The adsorption process, mainly chemical adsorption, conforms to the Lagergren second-order kinetic equation (R2 = 0.9952 and 0.9932). The adsorption isotherms have a higher fitting degree with the Langmuir model (R2 = 0.9964 and 0.9966), and the adsorption is a monolayer adsorption process. This study can provide a reference for treating heavy metals in acid mine drainage and resource utilization of fly ash.

9.
Sci Total Environ ; 927: 172159, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38575032

RESUMEN

Sediment contamination by heavy metals is a pressing environmental concern. While in situ metal stabilization techniques have shown promise, a great challenge remains in the simultaneous immobilization of multi-metals co-existing in contaminated sediments. This study aims to address this challenge by developing a practical method for stabilizing multi-metals by hydroxyapatite and calcium peroxide (HAP/CaO2) dosing strategies. Results showed that dosing 15.12 g of HAP/CaO2 at a ratio of 3:1 effectively transformed labile metals into stable fractions, reaching reaction kinetic equilibrium within one month with a pseudo-second-order kinetic (R2 > 0.98). The stable fractions of Nickel (Ni), Chromium (Cr), and lead (Pb) increased by approximately 16.9 %, 26.7 %, and 21.9 %, respectively, reducing heavy metal mobility and ensuring leachable concentrations complied with the stringent environmental Class I standard. Mechanistic analysis indicated that HAP played a crucial role in Pb stabilization, exhibiting a high rate of 0.0176 d-1, while Cr and Ni stabilization primarily occurred through the formation of hydroxide precipitates, as well as the slowly elevated pH (>8.5). Importantly, the proposed strategy poses a minimal environmental risk to benthic organisms exhibits almost negligible toxicity towards Vibrio fischeri and the Chironomus riparius, and saves about 71 % of costs compared to kaolinite. These advantages suggest the feasibility of HAP/CaO2 dosing strategies in multi-metal stabilization in contaminated sediments.


Asunto(s)
Durapatita , Peróxidos , Contaminantes Químicos del Agua , Durapatita/química , Contaminantes Químicos del Agua/análisis , Peróxidos/química , Metales Pesados , Sedimentos Geológicos/química , Restauración y Remediación Ambiental/métodos
10.
Materials (Basel) ; 17(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38591439

RESUMEN

In natural kaolinite lattices, Al3+ can potentially be substituted by cations such as Mg2+, Ca2+, and Fe3+, thereby influencing its adsorption characteristics towards rare earth elements like Sc3+. Density functional theory (DFT) has emerged as a crucial tool in the study of adsorption phenomena, particularly for understanding the complex interactions of rare earth elements with clay minerals. This study employed DFT to investigate the impact of these three dopant elements on the adsorption of hydrated Sc3+ on the kaolinite (001) Al-OH surface. We discerned that the optimal adsorption configuration for hydrated Sc3+ is Sc(H2O)83+, with a preference for adsorption at the deprotonated Ou sites. Among the dopants, Mg doping exhibited superior stability with a binding energy of -4.311 eV and the most negative adsorption energy of -1104.16 kJ/mol. Both Mg and Ca doping enhanced the covalency of the Al-O bond, leading to a subtle shift in the overall density of states towards higher energies, thereby augmenting the reactivity of the O atoms. In contrast, Fe doping caused a pronounced shift in the density of states towards lower energies. Compared to the undoped kaolinite, Mg and Ca doping further diminished the adsorption energy of hydrated Sc3+ and increased its coordination number, while Fe doping elevated the adsorption energy. This study offers profound insights into understanding the role of dopant elements in the adsorption of hydrated Sc3+ on kaolinite.

12.
Pharmacol Res ; 203: 107186, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38641176

RESUMEN

Chimeric antigen receptor (CAR)-modified T cell therapy has achieved remarkable efficacy in treating hematological malignancies, but it confronts many challenges in treating solid tumors, such as the immunosuppressive microenvironment of the solid tumors. These factors reduce the antitumor activity of CAR-T cells in clinical trials. Therefore, we used the immunocytokine interleukin-12 (IL-12) to enhance the efficacy of CAR-T cell therapy. In this study, we engineered CAR-IL12R54 T cells that targeted mesothelin (MSLN) and secreted a single-chain IL-12 fused to a scFv fragment R54 that recognized a different epitope on mesothelin. The evaluation of the anti-tumor activity of the CAR-IL12R54 T cells alone or in combination with anti-PD-1 antibody in vitro and in vivo was followed by the exploration of the functional mechanism by which the immunocytokine IL-12 enhanced the antitumor activity. CAR-IL12R54 T cells had potency to lyse mesothelin positive tumor cells in vitro. In vivo studies demonstrated that CAR-IL12R54 T cells were effective in controlling the growth of established tumors in a xenograft mouse model with fewer side effects than CAR-T cells that secreted naked IL-12. Furthermore, combination of PD-1 blockade antibody with CAR-IL12R54 T cells elicited durable anti-tumor responses. Mechanistic studies showed that IL12R54 enhanced Interferon-γ (IFN-γ) production and dampened the activity of regulatory T cells (Tregs). IL12R54 also upregulated CXCR6 expression in the T cells through the NF-κB pathway, which facilitated T cell infiltration and persistence in the tumor tissues. In summary, the studies provide a good therapeutic option for the clinical treatment of solid tumors.


Asunto(s)
Inmunoterapia Adoptiva , Interleucina-12 , Mesotelina , Receptores Quiméricos de Antígenos , Animales , Interleucina-12/inmunología , Interleucina-12/genética , Humanos , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Línea Celular Tumoral , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/antagonistas & inhibidores , Microambiente Tumoral/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/inmunología , Linfocitos T/inmunología
13.
Neuroscience ; 549: 84-91, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38460904

RESUMEN

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.


Asunto(s)
Recuperación de la Función , Traumatismos de la Médula Espinal , Médula Espinal , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/metabolismo , Animales , Recuperación de la Función/fisiología , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/fisiopatología , FN-kappa B/metabolismo , Masculino , Apoptosis/fisiología , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Sistema Linfático/fisiopatología , Sistema Linfático/patología , Edema/patología , Conducto Torácico/fisiopatología , Femenino , Micropartículas Derivadas de Células/metabolismo
14.
Int Immunopharmacol ; 130: 111674, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38387190

RESUMEN

Traumatic brain injury (TBI) can induce systemic coagulopathy and inflammation, thereby increasing the risk of mortality and disability. However, the mechanism causing systemic coagulopathy and inflammation following TBI remains unclear. In prior research, we discovered that brain-derived extracellular vesicles (BDEVs), originating from the injured brain, can activate the coagulation cascade and inflammatory cells. In this study, we primarily investigated how BDEVs affect systemic coagulopathy and inflammation in peripheral circulation. The results of cytokines and coagulation function indicated that BDEVs can lead to systemic coagulopathy and inflammation by influencing inflammatory factors and chemokines within 24 h. Furthermore, according to flow cytometry and blood cell counter results, we found that BDEVs induced changes in the blood count such as a reduced number of platelets and leukocytes and an increased percentage of neutrophils, macrophages, activated platelets, circulating platelet-EVs, and leukocyte-derived EVs. We also discovered that eliminating circulating BDEVs with lactadherin helped improve coagulopathy and inflammation, relieved blood cell dysfunction, and decreased the circulating platelet-EVs and leukocyte-derived EVs. Our research provides a novel viewpoint and potential mechanism of TBI-associated secondary damage.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Lesiones Traumáticas del Encéfalo , Vesículas Extracelulares , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Inflamación/complicaciones , Encéfalo , Trastornos de la Coagulación Sanguínea/etiología
15.
Chemosphere ; 346: 140538, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38303397

RESUMEN

To enhance the polarization distribution of electron cloud density on the catalyst surface, we have introduced a novel bimetallic-substituted dual-reaction center (DRC) catalyst (FeCo-γ-Al2O3) comprising iron (Fe) and cobalt (Co) for the decomplexation and mineralization of heavy metal complex Ni-EDTA in this study. Compared to the catalysts doped solely with Fe or Co, the bimetal-doped catalyst offered several advantages, including enhanced electron cloud polarization distribution, additional electron transfer pathway, and improved capacity of free radical generation. Through DFT calculations and EPR tests, we have elucidated the influences of the catalyst's adsorption toward Ni-EDTA and its decomplexation products on the electron transfer between the pollutant and the catalyst. The competition between the pollutants and H2O2 affects the generation of free radicals in both electron-rich Fe and Co centers as well as electron-deficient Al center. Building on these findings, we have proposed a plausible removal mechanism of Ni-EDTA using the heterogeneous Fenton-like catalyst FeCo-γ-Al2O3. This study sheds light on the potential of FeCo-γ-Al2O3 as a DRC catalyst and emphasizes the significance of pollutant characteristics in determining the catalyst's performance.


Asunto(s)
Electrones , Contaminantes Ambientales , Ácido Edético , Peróxido de Hidrógeno , Hierro , Catálisis , Cobalto
16.
Environ Toxicol ; 39(2): 562-571, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37449671

RESUMEN

BACKGROUND: Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years. METHODS: In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT-PCR. RESULTS: Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling. CONCLUSION: Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone-based therapeutic strategies.


Asunto(s)
Glioma , Transducción de Señal , Animales , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Glioma/genética , Quinasas Asociadas a rho/metabolismo , Temozolomida/farmacología , Temozolomida/uso terapéutico , Cumarinas/farmacología , Cumarinas/uso terapéutico
17.
Histol Histopathol ; 39(3): 381-390, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37366540

RESUMEN

BACKGROUND: The purpose of this study was to investigate the expression of CMTM6 in HCC tissues and its prognostic value, and to try to develop a nomogram prognostic model based on CMTM6. METHODS: In this retrospective study, immunohistochemical (IHC) staining was performed in 178 patients who underwent radical hepatectomy in the same surgical team. R software was used to construct the nomogram model. The Bootstrap sampling method was used for internal validation. RESULTS: CMTM6 is significantly expressed in HCC tissues and is closely associated with decreased overall survival (OS). PVTT (HR = 6.2, 95% CI: 3.06 12.6, P<0.001), CMTM6 (HR=2.30, 95% CI: 1.27 4.0, P=0.006) and MVI (HR=10.8, 95% CI: 4.19-27.6, P<0.001) were independent predictors of OS. The nomogram combined with CMTM6, PVTT and MVI was more predictive than the traditional TNM scoring system, and the prediction effects of 1-year and 3-year OS were accurate. CONCLUSIONS: The prognosis of a patient may be predicted using high levels of CMTM6 expression in HCC tissues, and the nomogram model including CMTM6 expression has the best predictive ability.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Nomogramas , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Pronóstico
18.
Gut Microbes ; 15(2): 2293312, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38087436

RESUMEN

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metformina , Humanos , Ratones , Animales , Intestinos , Verrucomicrobia/metabolismo
19.
Sensors (Basel) ; 23(21)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37960415

RESUMEN

This paper describes the design of a low-noise, high-speed readout-integrated circuit for use in InGaAs infrared focal plane arrays, and analyzes the working principle and noise index of the pixel circuit in detail. The design fully considers the dynamic range, noise, and power consumption of the pixel circuit in which a capacitance transimpedance amplifier structure is adopted as the input stage circuit, and chip fabrication via an XFAB 0.18 µm CMOS process is successfully realized. The ROIC adopts monolithic integration and implements various functions, such as windowing, subsampling, and different integration and readout modes. The ROIC reached an array scale of 32 × 32, a frame rate of 100 Hz, and a readout rate of 20 Mbps with an analog power consumption of less than 52 mW. The measurement results show that the input reference noise can be reduced to 143 e- via the CDS, and the fully customized scheme has certain advantages in the research of high-performance ROICs.

20.
Chemosphere ; 345: 140509, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37871873

RESUMEN

Biofilm-developed microplastics (MPs) may serve as important vectors for contaminants in aquatic environments. Elucidating the interactions between biofilm-developed MPs and coexisting contaminants is crucial for understanding the vector capacities of MPs. However, little is known about how the adverse effects of contaminants on MP surface-colonized biofilms influence their vector capacity. In this study, we aimed to investigate the interaction mechanism of biofilms colonizing the surface of MPs with coexisting contaminants using microcosm experiments and biofilm characterization techniques. The results indicated that the biofilm biomass on polystyrene increased over time, providing an additional abundance of oxygen-containing functional groups and promoting Cd accumulation by biofilm-developed polystyrene. Moreover, as a coexisting contaminant, Cd exerted adverse effects such as additional mortality of microorganisms and senescence and MP-colonized biofilm shedding. Consequently, the contaminant vector capacity of biofilm-developed MPs could be mitigated. Thus, the adverse effects of coexisting contaminants on biofilms influenced the ability of MPs to act as vectors in aquatic environments. Neglecting the negative effects of contaminants on biofilms may lead to an overestimation of the contaminant vector capacity of biofilm-developed MPs. This study provides support for more accurate assessment of the interactions between biofilm-developed MPs as vectors and contaminants in aquatic environments.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Microplásticos/toxicidad , Plásticos , Poliestirenos/toxicidad , Cadmio , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Biopelículas
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