Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
1.
Biofactors ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087587

RESUMEN

The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or enzyme-linked immunosorbent assay (ELISA), and cellular signaling as well as binding of related-signal proteins by Western blot, pull-down assay and kinase assay, and molecular modeling. The transactivation and expression of cyclooxygenase-2 (COX-2) gene as well as prostaglandin E2 (PGE2) secretion induced by LPS were inhibited by fisetin in a dose-dependent manner. Signaling transduction analysis demonstrated that fisetin selectively inhibited MKK4-JNK1/2 signaling to suppress the phosphorylation of transcription factor AP-1 without affecting the NF-κB and Jak2-Stat3 signaling as well as the phosphorylation of Src, Syk, and TAK1. Furthermore, in vitro and ex vivo pull-down assay using cell lysate or purified protein demonstrated that fisetin could bind directly to MKK4. Molecular modeling using the Molecular Operating Environment™ software indicated that fisetin docked into the ATP-binding pocket of MKK4 with a binding energy of -71.75 kcal/mol and formed a 1.70 Å hydrogen bound with Asp247 residue of MKK4. The IC50 of fisetin against MKK4 was estimated as 2.899 µM in the kinase assay, and the ATP-competitive effect was confirmed by ATP titration. Taken together, our data revealed that fisetin is a potent selective ATP-competitive MKK4 inhibitor to suppress MKK4-JNK1/2-AP-1 cascade for inhibiting LPS-induced inflammation.

2.
Phytother Res ; 38(8): 3954-3972, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837315

RESUMEN

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Neoplasias Colorrectales , Curcumina , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteína p53 Supresora de Tumor , Ferroptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Curcumina/farmacología , Animales , Ratones , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Ratones Desnudos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Peroxidación de Lípido/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Masculino , Simulación del Acoplamiento Molecular , Proliferación Celular/efectos de los fármacos
3.
Biomed Pharmacother ; 175: 116715, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38739993

RESUMEN

Ischemic stroke, a devastating disease associated with high mortality and disability worldwide, has emerged as an urgent public health issue. A-kinase anchoring proteins (AKAPs) are a group of signal-organizing molecules that compartmentalize and anchor a wide range of receptors and effector proteins and have a major role in stabilizing mitochondrial function and promoting neurodevelopmental development in the central nervous system (CNS). Growing evidence suggests that dysregulation of AKAPs expression and activity is closely associated with oxidative stress, ion disorder, mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in ischemic stroke. However, the underlying mechanisms remain inadequately understood. This review provides a comprehensive overview of the composition and structure of A-kinase anchoring protein (AKAP) family members, emphasizing their physiological functions in the CNS. We explored in depth the molecular and cellular mechanisms of AKAP complexes in the pathological progression and risk factors of ischemic stroke, including hypertension, hyperglycemia, lipid metabolism disorders, and atrial fibrillation. Herein, we highlight the potential of AKAP complexes as a pharmacological target against ischemic stroke in the hope of inspiring translational research and innovative clinical approaches.


Asunto(s)
Proteínas de Anclaje a la Quinasa A , Accidente Cerebrovascular Isquémico , Humanos , Proteínas de Anclaje a la Quinasa A/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo
4.
Molecules ; 29(10)2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38792269

RESUMEN

Quercetin, a flavonoid polyphenol found in many plants, has garnered significant attention due to its potential cancer chemoprevention. Our previous studies have shown that acetyl modification of the hydroxyl group of quercetin altered its antitumor effects in HepG2 cells. However, the antitumor effect in other cancer cells with different gene mutants remains unknown. In this study, we investigated the antitumor effect of quercetin and its methylated derivative 3,3',4',7-O-tetramethylquercetin (4Me-Q) and acetylated derivative 3,3',4',7-O-tetraacetylquercetin (4Ac-Q) on two human breast cancer cells, MCF-7 (wt-p53, caspase-3-ve) and MDA-MB-231 (mt-p53, caspase-3+ve). The results demonstrated that 4Ac-Q exhibited significant cell proliferation inhibition and apoptosis induction in both MCF-7 and MDA-MB-231 cells. Conversely, methylation of quercetin was found to lose the activity. The human apoptosis antibody array revealed that 4Ac-Q might induce apoptosis in MCF-7 cells via a p53-dependent pathway, while in MDA-MB-231 cells, it was induced via a caspase-3-dependent pathway. Furthermore, an evaluation using a superoxide inhibitor, MnTBAP, revealed 4Ac-Q-induced apoptosis in MCF-7 cells in a superoxide-independent manner. These findings provide valuable insights into the potential of acetylated quercetin as a new approach in cancer chemoprevention and offer new avenues for health product development.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Proliferación Celular , Quercetina , Humanos , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Acetilación/efectos de los fármacos , Apoptosis/efectos de los fármacos , Metilación , Femenino , Proliferación Celular/efectos de los fármacos , Células MCF-7 , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proteína p53 Supresora de Tumor/metabolismo , Caspasa 3/metabolismo
5.
Food Funct ; 15(9): 4852-4861, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38573228

RESUMEN

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.


Asunto(s)
Dieta Alta en Grasa , Mitocondrias , Resultado del Embarazo , Resveratrol , Útero , Animales , Resveratrol/farmacología , Femenino , Embarazo , Ratones , Dieta Alta en Grasa/efectos adversos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Útero/metabolismo , Útero/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratones Endogámicos C57BL , Obesidad/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo
6.
J Am Chem Soc ; 146(11): 7341-7351, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38442250

RESUMEN

The C2H2 separation from CO2 and C2H4 is of great importance yet highly challenging in the petrochemical industry, owing to their similar physical and chemical properties. Herein, the pore nanospace engineering of cage-like mixed-ligand MFOF-1 has been accomplished via contracting the size of the pyridine- and carboxylic acid-functionalized linkers and introducing a fluoride- and sulfate-bridging cobalt cluster, based on a reticular chemistry strategy. Compared with the prototypical MFOF-1, the constructed FJUT-1 with the same topology presents significantly improved C2H2 adsorption capacity, and selective C2H2 separation performance due to the reduced cage cavity size, functionalized pore surface, and appropriate pore volume. The introduction of fluoride- and sulfate-bridging cubane-type tetranuclear cobalt clusters bestows FJUT-1 with exceptional chemical stability under harsh conditions while providing multiple potential C2H2 binding sites, thus rendering the adequate ability for practical C2H2 separation application as confirmed by the dynamic breakthrough experiments under dry and humid conditions. Additionally, the distinct binding mechanism is suggested by theoretical calculations in which the multiple supramolecular interactions involving C-H···O, C-H···F, and other van der Waals forces play a critical role in the selective C2H2 separation.

7.
Cell Prolif ; 57(8): e13636, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38504474

RESUMEN

Cardiovascular disease (CVD) is a group of diseases that primarily affect the heart or blood vessels, with high disability and mortality rates, posing a serious threat to human health. The causative factors, pathogenesis, and characteristics of common CVD differ, but they all involve common pathological processes such as inflammation, oxidative stress, and fibrosis. S100A9 belongs to the S100 family of calcium-binding proteins, which are mainly secreted by myeloid cells and bind to the Toll-like receptor 4 and receptor for advanced glycation end products and is involved in regulating pathological processes such as inflammatory response, fibrosis, vascular calcification, and endothelial barrier function in CVD. The latest research has found that S100A9 is a key biomarker for diagnosing and predicting various CVD. Therefore, this article reviews the latest research progress on the diagnostic and predictive, and therapeutic value of S100A9 in inflammatory-related CVD such as atherosclerosis, myocardial infarction, and arterial aneurysm and summarizes its molecular mechanisms in the progression of CVD, aiming to explore new predictive methods and to identify potential intervention targets for CVD in clinical practice.


Asunto(s)
Calgranulina B , Enfermedades Cardiovasculares , Humanos , Calgranulina B/metabolismo , Enfermedades Cardiovasculares/metabolismo , Biomarcadores/metabolismo , Inflamación/metabolismo , Animales , Estrés Oxidativo
8.
Anim Nutr ; 15: 341-349, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38053801

RESUMEN

Rosemary extracts have been widely used as feed additives in recent years. This study aimed to investigate the effects of rosmarinic acid (RA) and ursolic acid (UA), the main active components of rosemary, on growth performance, meat quality and lipid metabolism in finishing pigs. A total of 72 finishing pigs (Landrace; initial age of 150 d) were randomly divided into 3 treatments with 8 replicates of 3 pigs each, and fed a basal diet or diet containing 500 mg/kg of RA or UA. The results showed that dietary supplementation of RA or UA had no significant effect on the growth performance and carcass traits of finishing pigs (P > 0.05). However, both RA and UA significantly increased the triglyceride (TG) level in soleus muscle (P < 0.001). Supplementation of RA increased the expression of genes related to lipogenesis and transport including fatty acid synthase (FAS) (P < 0.001), sterol regulatory element binding protein-1c (SREBP1c) (P < 0.001) and peroxisome proliferator-activated receptor γ (PPARγ) (P < 0.05), while UA increased the expression of fatty acid transport protein 1 (FATP1), a gene related to lipid uptake (P < 0.05). However, RA reduced the expression of adipogenesis-related gene acetyl-coenzyme A carboxylase α (ACCα) (P < 0.01). Characterization of cecal microbiota indicated that RA increased the microbial richness (chao 1, P < 0.001) and diversity (observed species, P < 0.01). Further analysis of the genera revealed that RA increased the relative abundance of Bacteroides and g-UCG-005 (P < 0.05), and UA enriched Prevotella (P < 0.001). Correlation analysis showed that g-UCG-005 was positively correlated with the expression of FAS, carnitine palmitoyl transferase 1B (CPT1B), SREBP1c and PPARγ (P < 0.01). In conclusion, dietary supplementation of RA or UA may increase fat deposition in muscle of finishing pigs by regulating lipid metabolism and gut microbiota.

9.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38139286

RESUMEN

Quercetin forms complexes with various metals due to its structural attributes. It predominantly exhibits chelating activity at the 3-hydroxy/4-carbonyl group. Previously, coordination in synthetically obtained quercetin-zinc (II) complexes has been limited to this group. However, the expanded coordination observed in quercetin-iron complexes has opened avenues for diverse applications. Thus, synthesizing novel quercetin-zinc complexes with different coordination positions is a significant advance. In our study, we not only synthesized and comprehensively characterized a new quercetin-zinc (II) complex, Zn-Q, but also evaluated the structure and bioactivity of chelate complexes (Q+Zn) derived from co-treatment in cell culture mediums. The structure of the new compound Zn-Q was comprehensively characterized using 1D 1H and 2D correlation spectroscopy (COSY), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometer (ESI-MS), and X-ray diffraction analysis (XRD) analysis. Subcellular localization and absorption of these zinc (II) complexes were determined using the ZnAF-2 DA zinc ion fluorescence probe. Throughout the experiments, both Zn-Q and Q+Zn exhibited significant antioxidant, cell growth inhibitory, and anticancer effects in HepG2 and HCT116 cells, with Zn-Q showing the highest potential for inducing apoptosis via the caspase pathway. Tracking intracellular zinc complex absorption using zinc fluorescent probes revealed zinc (II) localization around the cell nucleus. Interestingly, there was a proportional increase in intracellular quercetin absorption in conjunction with zinc (II) uptake. Our research highlights the advantages of quercetin complexation with zinc (II): enhanced anticancer efficacy compared to the parent compound and improved bioavailability of both quercetin and zinc (II). Notably, our findings, which include enhanced intracellular uptake of both quercetin and zinc (II) upon complex formation and its implications in apoptosis, contribute significantly to the understanding of metal-polyphenol complexes. Moving forward, comprehensive functional assessments and insights into its mechanism of action, supported by animal studies, are anticipated.


Asunto(s)
Complejos de Coordinación , Zinc , Humanos , Animales , Zinc/química , Quercetina/farmacología , Quercetina/química , Células HCT116 , Espectroscopía Infrarroja por Transformada de Fourier , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Apoptosis
10.
iScience ; 26(11): 108306, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38026209

RESUMEN

Human pluripotent stem cell (hPSC)-derived neurons have shown promise in treating spinal cord injury (SCI). We previously showed that hPSC-derived dorsal spinal γ-aminobutyric acid (GABA) neurons can alleviate spasticity and promote locomotion in rats with SCI, but their long-term safety remains elusive. Here, we characterized the long-term fate and safety of human dorsal spinal GABA neural progenitor cells (NPCs) in naive rats over one year. All grafted NPCs had undergone differentiation, yielding mainly neurons and astrocytes. Fully mature human neurons grew many axons and formed numerous synapses with rat neural circuits, together with mature human astrocytes that structurally integrated into the rat spinal cord. The sensorimotor function of rats was not impaired by intraspinal transplantation, even when human neurons were activated or inhibited by designer receptors exclusively activated by designer drugs (DREADDs). These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

11.
Gut Microbes ; 15(1): 2238959, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37505920

RESUMEN

Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , LDL-Colesterol , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Factor 1 de Crecimiento de Fibroblastos/farmacología , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Hígado/metabolismo , Dieta Alta en Grasa/efectos adversos
12.
Sheng Wu Gong Cheng Xue Bao ; 39(6): 2284-2312, 2023 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-37401595

RESUMEN

Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.


Asunto(s)
Yarrowia , Levaduras , Levaduras/genética , Yarrowia/genética , Yarrowia/metabolismo , Edición Génica , Ingeniería Metabólica
13.
ACS Appl Mater Interfaces ; 15(25): 30394-30401, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37327481

RESUMEN

The separation of CO2 from the industrial post-combustion flue gas is of great importance to reduce the increasingly serious greenhouse effect, yet highly challenging due to the extremely high stability, low cost, and high separation performance requirements for adsorbents under the practical operating conditions. Herein, we report a robust squarate-cobalt metal-organic framework (MOF), FJUT-3, featuring an ultra-small 1D square channel decorated with -OH groups, for CO2/N2 separation. Remarkably, FJUT-3 not only has excellent stability under harsh chemical conditions but also presents low-cost property for scale-up synthesis. Moreover, FJUT-3 shows excellent CO2 separation performance under various humid and temperature conditions confirmed by the transient breakthrough experiments, thus enabling FJUT-3 with adequate potentials for industrial CO2 capture and removal. The distinct CO2 adsorption mechanism is well elucidated by theoretical calculations, in which the hierarchical C···OCO2, C-O···CCO2, and O-H···OCO2 interactions play a vital synergistic role in the selective CO2 adsorption process.

14.
Inorg Chem ; 62(21): 8058-8063, 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37172273

RESUMEN

The development of metal-organic framework (MOF) adsorbents with a potential molecule sieving effect for CO2 capture and separation from flue gas is of critical importance for reducing the CO2 emissions to the atmosphere yet challenging. Herein, a cagelike MOF with a suitable cage window size falling between CO2 and N2 and the cavity has been constructed to evaluate its CO2/N2 separation performance. It is noteworthy that the introduction of coordinated dimethylamine (DMA) and N,N'-dimethylformamide (DMF) molecules not only significantly reduces the cage window size but also enhances the framework-CO2 interaction via C-H···O hydrogen bonds, as proven by molecular modeling, thus leading to an improved CO2 separation performance. Moreover, transient breakthrough experiments corroborate the efficient CO2/N2 separation, revealing that the introduction of DMA and DMF molecules plays a vital role in the separation of a CO2/N2 gas mixture.

15.
Theranostics ; 13(6): 1826-1842, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37064881

RESUMEN

Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the α7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.


Asunto(s)
Hipertensión Pulmonar , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Células Th17/metabolismo , Donepezilo/efectos adversos , Donepezilo/metabolismo , Pulmón/patología , Fibrosis , Bleomicina/toxicidad
16.
Bioengineering (Basel) ; 10(2)2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36829621

RESUMEN

With the rapid development of artificial intelligence technology, the exploration and application in the field of intelligent education has become a research hotspot of increasing concern. In the actual classroom scenarios, students' classroom behavior is an important factor that directly affects their learning performance. Specifically, students with poor self-management abilities, particularly specific developmental disorders, may face educational and academic difficulties owing to physical or psychological factors. Therefore, the intelligent perception and identification of school-aged children's classroom behaviors are extremely valuable and significant. The traditional method for identifying students' classroom behavior relies on statistical surveys conducted by teachers, which incurs problems such as being time-consuming, labor-intensive, privacy-violating, and an inaccurate manual intervention. To address the above-mentioned issues, we constructed a motion sensor-based intelligent system to realize the perception and identification of classroom behavior in the current study. For the acquired sensor signal, we proposed a Voting-Based Dynamic Time Warping algorithm (VB-DTW) in which a voting mechanism is used to compare the similarities between adjacent clips and extract valid action segments. Subsequent experiments have verified that effective signal segments can help improve the accuracy of behavior identification. Furthermore, upon combining with the classroom motion data acquisition system, through the powerful feature extraction ability of the deep learning algorithms, the effectiveness and feasibility are verified from the perspectives of the dimensional signal characteristics and time series separately so as to realize the accurate, non-invasive and intelligent children's behavior detection. To verify the feasibility of the proposed method, a self-constructed dataset (SCB-13) was collected. Thirteen participants were invited to perform 14 common class behaviors, wearing motion sensors whose data were recorded by a program. In SCB-13, the proposed method achieved 100% identification accuracy. Based on the proposed algorithms, it is possible to provide immediate feedback on students' classroom performance and help them improve their learning performance while providing an essential reference basis and data support for constructing an intelligent digital education platform.

17.
iScience ; 25(11): 105371, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36345343

RESUMEN

As an emerging new class of semiconductor nanomaterials, halide perovskite (ABX3, X = Cl, Br, or I) nanocrystals (NCs) are attracting increasing attention owing to their great potential in optoelectronics and beyond. This field has experienced rapid breakthroughs over the past few years. In this comprehensive review, halide perovskite NCs that are either freestanding or embedded in a matrix (e.g., perovskites, metal-organic frameworks, glass) will be discussed. We will summarize recent progress on the synthesis and post-synthesis methods of halide perovskite NCs. Characterizations of halide perovskite NCs by using a variety of techniques will be present. Tremendous efforts to tailor the optical and electronic properties of halide perovskite NCs in terms of manipulating their size, surface, and component will be highlighted. Physical insights gained on the unique optical and charge-carrier transport properties will be provided. Importantly, the growing potential of halide perovskite NCs for advancing optoelectronic applications and beyond including light-emitting devices (LEDs), solar cells, scintillators and X-ray imaging, lasers, thin-film transistors (TFTs), artificial synapses, and light communication will be extensively discussed, along with prospecting their development in the future.

18.
Front Bioeng Biotechnol ; 10: 1020444, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36312553

RESUMEN

The outbreak of the coronavirus (COVID-19) has heightened awareness of the importance of quick and easy testing. The convenience, speed, and timely results from point-of-care testing (POCT) in all vitro diagnostic devices has drawn the strong interest of researchers. However, there are still many challenges in the development of POCT devices, such as the pretreatment of samples, detection sensitivity, specificity, and so on. It is anticipated that the unique properties of nanomaterials, e.g., their magnetic, optical, thermal, and electrically conductive features, will address the deficiencies that currently exist in POCT devices. In this review, we mainly analyze the work processes of POCT devices, especially in nucleic acid detection, and summarize how novel nanomaterials used in various aspects of POCT products can improve performance, with the ultimate aims of offering new ideas for the application of nanomaterials and the overall development of POCT devices.

19.
Front Bioeng Biotechnol ; 10: 955713, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36061450

RESUMEN

Herpes disease is caused by Herpes simplex virus (HSV). It has become one of the global health problems. This paper reports a method for HSV type testing. First specific primers sequence for HSV-1 and HSV-2 were selected, designed, and synthesized. Then, these amplification products were proved by sequencing and analysis. Lastly, we optimized the reaction system and PCR reaction program by orthogonal design and sensitivity testing. Results showed that the lowest concentration in HSV-type testing is about 6.67 × 106 copies/ml. Moreover, the specificity of detection was very high. So, this method has very great potentials for HSV type testing in clinical practice.

20.
Saudi Pharm J ; 30(8): 1079-1087, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36164567

RESUMEN

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA