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1.
J Hazard Mater ; 479: 135682, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39236542

RESUMEN

Perfluorooctanoic acid (PFOA), an emerging pollutant, has been frequently detected in organic solid waste. It becomes a major concern for compost application, but studies on its toxic effects during composting are rare. This study evaluated the impact of PFOA presence at the environmentally relevant level on the humification process and microbiology during composting. The results showed that the PFOA presence (15.5 µg/kg dry) caused 45.5 % and 40.5 % decreases in the total organic carbon and humic acid-like substances, respectively. PFOA negatively affected microbial activity during the thermophilic period, as evidenced by the increases in reactive oxygen species and lactate dehydrogenase concentration. It altered the microbial community with an enrichment of Bacteroidota, conducive to resisting press. Unexpectedly, the PFOA presence induced hormesis at the maturity period, consistent with stimulated carbon metabolism (i.e., glycolysis and oxidative phosphorylation). The modulated microbial metabolism stimulated the catabolic metabolism of small-molecule humus precursors and reduced intracellular quinone availability. Furthermore, the secretion of auxiliary activities for crude fiber degradation was suppressed, which decreased the generation of extracellular quinone, and thereby impeded the humification process. These findings deciphered the metabolic response of composting to PFOA presence and highlighted the potential carbon loss of PFOA-containing composting.

2.
Front Pharmacol ; 15: 1415145, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161900

RESUMEN

Sepsis-induced acute lung injury (ALI) is a major cause of death among patients with sepsis in intensive care units. By analyzing a model of sepsis-induced ALI using lipopolysaccharide (LPS) and cecal ligation and puncture (CLP), treatment methods and strategies to protect against ALI were discussed, which could provide an experimental basis for the clinical treatment of sepsis-induced ALI. Recent studies have found that an imbalance in autophagy, ferroptosis, and pyroptosis is a key mechanism that triggers sepsis-induced ALI, and regulating these death mechanisms can improve lung injuries caused by LPS or CLP. This article summarized and reviewed the mechanisms and regulatory networks of autophagy, ferroptosis, and pyroptosis and their important roles in the process of LPS/CLP-induced ALI in sepsis, discusses the possible targeted drugs of the above mechanisms and their effects, describes their dilemma and prospects, and provides new perspectives for the future treatment of sepsis-induced ALI.

3.
Sensors (Basel) ; 24(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39204939

RESUMEN

We present a sensor array of microscale organic electrochemical transistors (OECTs) using poly (3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) as the channel material. The devices show high sensitivity and selectivity to detect dopamine (DA) with platinum (Pt) as a pseudo-reference gate electrode. First, we describe the wafer-scale fabrication process for manufacturing the PEDOT:PSS OECTs, and then we introduce a dilution method to adjust the thickness of the PEDOT:PSS film. Next, we investigate the effect of the film thickness on the sensitivity of DA detection. Reducing the film thickness enhances the sensitivity of DA detection within the concentration range of 1 µM to 100 µM. The OECTs show impressive sensitivitywith a limit of detection (LoD) as low as 1 nM and a high selectivity against uric acid (UA) and ascorbic acid (AA). Finally, we modify the surface of the Pt gate electrode with chitosan to improve the selectivity of OECTs at high concentrations of up to 100 µM to expand the detection range.

4.
J Sci Food Agric ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967243

RESUMEN

BACKGROUND: Mycotoxin contamination of food has been gaining increasing attention. Hidden mycotoxins that interact with biological macromolecules in food could make the detection of mycotoxins less accurate, potentially leading to the underestimation of the total exposure risk. Interactions of the mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) with high-molecular glutenin were explored in this study. RESULTS: The recovery rates of AOH and AME (1, 2, and 10 µg kg-1) in three types of grains (rice, corn, and wheat) were relatively low. Molecular dynamics (MD) simulations indicated that AOH and AME bound to glutenin spontaneously. Hydrogen bonds and π-π stacking were the primary interaction forces at the binding sites. Alternariol with one additional hydroxyl group exhibited stronger binding affinity to glutenin than AME when analyzing average local ionization energy. The average interaction energy between AOH and glutenin was -80.68 KJ mol-1, whereas that of AME was -67.11 KJ mol-1. CONCLUSION: This study revealed the mechanisms of the interactions between AOH (or AME) and high-molecular glutenin using MD and molecular docking. This could be useful in the development of effective methods to detect pollution levels. These results could also play an important role in the evaluation of the toxicological properties of bound altertoxins. © 2024 Society of Chemical Industry.

5.
BMC Genomics ; 25(1): 689, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003448

RESUMEN

BACKGROUND: The holothurians, commonly known as sea cucumbers, are marine organisms that possess significant dietary, nutritional, and medicinal value. However, the National Center for Biotechnology Information (NCBI) currently possesses only approximately 70 complete mitochondrial genome datasets of Holothurioidea, which poses limitations on conducting comprehensive research on their genetic resources and evolutionary patterns. In this study, a novel species of sea cucumber belonging to the genus Benthodytes, was discovered in the western Pacific Ocean. The genomic DNA of the novel sea cucumber was extracted, sequenced, assembled and subjected to thorough analysis. RESULTS: The mtDNA of Benthodytes sp. Gxx-2023 (GenBank No. OR992091) exhibits a circular structure spanning 17,386 bp, comprising of 13 protein-coding genes (PCGs), 24 non-coding RNAs (2 rRNA genes and 22 tRNA genes), along with two putative control regions measuring 882 bp and 1153 bp, respectively. It exhibits a high AT% content and negative AT-skew, which distinguishing it from the majority of sea cucumbers in terms of environmental adaptability evolution. The mitochondrial gene homology between Gxx-2023 and other sea cucumbers is significantly low, with less than 91% similarity to Benthodytes marianensis, which exhibits the highest level of homology. Additionally, its homology with other sea cucumbers is below 80%. The mitogenome of this species exhibits a unique pattern in terms of start and stop codons, featuring only two types of start codons (ATG and ATT) and three types of stop codons including the incomplete T. Notably, the abundance of AT in the Second position of the codons surpasses that of the First and Third position. The gene arrangement of PCGs exhibits a relatively conserved pattern, while there exists substantial variability in tRNA. Evolutionary analysis revealed that it formed a distinct cluster with B. marianensis and exhibited relatively distant phylogenetic relationships with other sea cucumbers. CONCLUSIONS: These findings contribute to the taxonomic diversity of sea cucumbers in the Elasipodida order, thereby holding significant implications for the conservation of biological genetic resources, evolutionary advancements, and the exploration of novel sea cucumber resources.


Asunto(s)
Evolución Molecular , Genoma Mitocondrial , Filogenia , Pepinos de Mar , Animales , Pepinos de Mar/genética , ARN de Transferencia/genética , Composición de Base
6.
Biosens Bioelectron ; 261: 116487, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38870829

RESUMEN

A new di-recognition nitrogen-doped carbon dot nanosurface aptamer molecularly imprinted polymer (CDNAg@MIPApt) nanocatalytic di-functional probe was prepared by microwave irradiation. The probe was utilized nitrogen-doped silver carbon dots (CDNAg) as the matrix, glyphosate (Gly) as the template molecule, α-methyl acrylate as the monomer, ethylene glycol dimethacrylate as the cross-linker, and aptamer as the biorecognition element. It could not only recognize Gly but also exhibits catalytic amplification function. It was found that CDNAg@MIPApt catalyzed the redox reaction of polyethylene glycol 400 (PEG400)-AgNO3 to generate silver nanoparticles (AgNPs). The AgNPs indicator component exhibit the effects of surface-enhanced Raman scattering (SERS), resonance Rayleigh scattering (RRS) and surface plasmon resonance absorption (Abs). In the presence of Gly, it binds to the surface imprinted site of CDNAg@MIPApt, to reduce AgNPs generation due to the catalytic activity of CDNAg@MIPApt decreasing. Thus, the SERS/RRS/Abs signal values decreased linearly. The linear ranges of SERS/RRS/Abs assay were 0.1-2.5 nM, 0.25-2.75 nM and 0.5-5 nM respectively. The detection limits were 0.034 nM, 0.071 nM and 0.18 nM Gly.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Glicina , Glifosato , Límite de Detección , Nanopartículas del Metal , Polímeros Impresos Molecularmente , Plata , Espectrometría Raman , Glicina/química , Glicina/análogos & derivados , Plata/química , Polímeros Impresos Molecularmente/química , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , Resonancia por Plasmón de Superficie/métodos , Herbicidas/análisis , Herbicidas/química , Carbono/química
7.
Fitoterapia ; 175: 105935, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38580032

RESUMEN

Buyang Huanwu Decoction (BHD) has been effective in treating ischemic stroke (IS). However, its mechanism of action remains unclear. The study intended to explore the potential mechanism of BHD against IS using systems pharmacology, proteomics, and animal experiments. The active components of BHD were identified from UPLC-Q-TOF-MS and literature mining. Systems pharmacology and proteomics were employed to investigate the underlying mechanism of BHD against IS. The AutoDock tool was used for molecular docking. A middle cerebral artery occlusion (MCAO) model rat was utilized to explore the therapeutic benefits of BHD. The rats were divided into sham, model, BHD (5, 10, 20 g/kg, ig) groups. The neurological scores, pathological section characteristics, brain infarct volumes, inflammatory cytokines, and signaling pathways were investigated in vivo experiments. The results of systems pharmacology showed that 13 active compounds and 112 common targets were screened in BHD. The docking results suggested that the active compounds in BHD had a high affinity for the key targets. In vivo experiments demonstrated that BHD exhibited neuroprotective benefits by lowering the neurological score, the volume of the cerebral infarct, the release of inflammatory cytokines, and reducing neuroinflammatory damage in MCAO rats. Furthermore, BHD decreased TNF-α and CD38 levels while increasing ATP2B2, PDE1A, CaMK4, p-PI3K, and p-AKT. Combined with systems pharmacology and proteomic studies, we confirmed that PI3K-Akt and calcium signaling pathways are the key mechanisms for BHD against IS. Furthermore, this study demonstrated the feasibility of combining proteomics with systems pharmacology to study the mechanism of herbal medicine.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Infarto de la Arteria Cerebral Media , Accidente Cerebrovascular Isquémico , Simulación del Acoplamiento Molecular , Farmacología en Red , Fármacos Neuroprotectores , Proteómica , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratas , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Citocinas/metabolismo
8.
Int J Biol Macromol ; 267(Pt 2): 131422, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614187

RESUMEN

Foam materials have been widely used in cushioning packaging to ensure the integrity of products inside by absorbing energy and preventing collision. However, the extensive use of petroleum-based plastic foams may exacerbate environmental pollution and consume large amounts of energy. Therefore, there has been an increasing focus on producing high-performance and environmentally friendly foams in recent years. In this study, we developed a simple approach for manufacturing cellulose fiber-based capillary foams featuring superior stability and three-dimensional (3D) backbone network cross-linking structure composed of polyvinyl alcohol (PVA) and cationic starch (CS). The resultant capillary foam showed low density (0.154 g/cm3), superior mechanical properties (elastic modulus ranging from 77 to 501 kPa), high energy absorbing efficiency (32.8 %), and low cushioning coefficient (3.0). Besides, the end-of-life cellulose fiber-based capillary foam can be easily recycled for use, showing an attractive closed-loop cycle process. This study presents a unique option for creating affordable, eco-friendly, and malleable foams, demonstrating the potential to substitute the currently used petroleum-based foams in the packaging, food, and transport industries.


Asunto(s)
Celulosa , Alcohol Polivinílico , Celulosa/química , Alcohol Polivinílico/química , Almidón/química , Reciclaje
9.
J Gynecol Oncol ; 35(5): e68, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38456590

RESUMEN

OBJECTIVE: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. METHODS: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry. Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively. Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model. RESULTS: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo. CONCLUSION: We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.


Asunto(s)
Proteína Quinasa CDC2 , Neoplasias Endometriales , Cinesinas , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt , Femenino , Humanos , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/genética , Proteína Quinasa CDC2/metabolismo , Proteína Quinasa CDC2/genética , Fosforilación , Línea Celular Tumoral , Animales , Cinesinas/metabolismo , Cinesinas/genética , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular , Proliferación Celular , Apoptosis , Transducción de Señal , Persona de Mediana Edad
10.
J Control Release ; 368: 208-218, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38395156

RESUMEN

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Humanos , Animales , Ratones , Nanovacunas , Neoplasias/terapia , Antígenos de Neoplasias , Ovalbúmina , Inmunoglobulina M , Ratones Endogámicos C57BL
11.
Int J Urol ; 31(5): 568-574, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38339874

RESUMEN

OBJECTIVES: This study aimed to establish a nomogram for predicting the probability of testicular salvage after testicular torsion in children. METHODS: We retrospectively collected data of children with testicular torsion who were treated at Shenzhen Children's Hospital between September 2005 and August 2022. Of the training cohort, 113 patients who underwent orchiectomy and five with testicular atrophy after orchiopexy were included in the failed testicular salvage group. Additionally, 37 patients who underwent orchiopexy without postoperative testicular atrophy were included in the successful testicular salvage group. The predictive factors affecting testicular salvage were determined using univariate and multivariate logistic regression analyses; a nomogram was constructed. The nomogram was verified using data from the validation group. RESULTS: Using multivariate logistic regression analysis, the independent risk factors of testicular salvage after testicular torsion were symptom duration (p = 0.034), intratesticular blood flow (p = 0.003), spermatic cord torsion degree (p = 0.037), and monocyte count (odds ratio: 0.012, p = 0.036). A nomogram was established based on these four risk factors. In the training cohort, the area under the receiver operating characteristic curve was 0.969. The area under the receiver operating characteristic curve of the verification cohort was 0.965, indicating good discrimination ability of the nomogram. Increased symptom duration without intratesticular blood flow increased the monocyte count and spermatic cord torsion degree and decreased the success rate of testicular salvage. CONCLUSION: This prediction model could obtain the corresponding probability of testicular salvage according to the clinical characteristics of different patients with testicular torsion, providing reference for clinicians and parents.


Asunto(s)
Nomogramas , Orquiectomía , Orquidopexia , Torsión del Cordón Espermático , Testículo , Humanos , Masculino , Torsión del Cordón Espermático/cirugía , Torsión del Cordón Espermático/diagnóstico , Niño , Estudios Retrospectivos , Factores de Riesgo , Preescolar , Testículo/cirugía , Testículo/patología , Curva ROC , Adolescente , Terapia Recuperativa/estadística & datos numéricos , Lactante , Modelos Logísticos , Atrofia , Resultado del Tratamiento
12.
Eur J Med Chem ; 266: 116082, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38232462

RESUMEN

Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R-8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R-8i are poor (T1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure-activity relationship study of thiazolidine-4-one sulfone inhibitors from R-8i, which led to the discovery of compound 68. Compound 68 had a potent cellular activity with an IC50 value of 0.217 µM, much higher half-life (T1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile (in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma.


Asunto(s)
Antineoplásicos , Neoplasias Óseas , Osteosarcoma , Humanos , Ratones , Animales , Preparaciones Farmacéuticas , Relación Estructura-Actividad , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral
13.
Pediatr Surg Int ; 40(1): 34, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38214758

RESUMEN

PURPOSE: To evaluate the feasibility of single-site laparoscopic orchiopexy for palpable undescended testes in children. METHODS: We prospectively studied patients with undescended testes between July 2021 and June 2022. In total, 223 patients were included in our study: 105 underwent single-site laparoscopic orchiopexy and 118 underwent conventional laparoscopic orchiopexy. During single-site laparoscopic orchiopexy, 3 ports were inserted within the umbilicus. RESULTS: No differences were observed between the groups in terms of age and laterality. For unilateral undescended testes, the operating time was longer in the single site group than in the conventional group at the early stages (55.31 ± 12.04 min vs. 48.14 ± 14.39 min, P = 0.007), but it was similar to the conventional group at the later stages (48.82 ± 13.49 min vs. 48.14 ± 14.39 min, P = 0.78). Testicular ascent occurred in one patient from each group. There was no significant difference in the success rate between the single-site group and the conventional group (99.0% vs. 99.2%, P = 0.93). In the single-site group, no visible abdominal scarring was observed, while in the conventional group, there were two noticeable scars on the abdomen. CONCLUSION: Single-site laparoscopic orchiopexy offers superior cosmetic results and comparable success rates compared to conventional laparoscopic orchiopexy for palpable undescended testes.


Asunto(s)
Cavidad Abdominal , Criptorquidismo , Laparoscopía , Niño , Masculino , Humanos , Lactante , Criptorquidismo/cirugía , Orquidopexia/métodos , Testículo/cirugía , Estudios Prospectivos , Laparoscopía/métodos , Resultado del Tratamiento
14.
Bioresour Technol ; 393: 130067, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37989418

RESUMEN

Electrical assistance is an effective strategy for promoting anaerobic digestion (AD) under ammonia stress. However, the underlying mechanism of electrical assistance affecting AD is insufficiently understood. Here, electrical assistance to AD under 5 g N/L ammonia stress was provided, by employing a 0.6 V voltage to the carbon electrodes. The results demonstrated remarkable enhancements in methane production (104.6 %) and the maximal methane production rate (207.7 %). The critical segment facilitated by electro-stimulation was the microbial metabolism of propionate-to-methane, rather than ammonia removal. Proteins in extracellular polymer substances were enriched, boosting microbial resilience to ammonia intrusion. Concurrently, the promoted humic/fulvic-substances amplified the microbial electron transfer capacity. Metagenomics analysis identified the upsurge of propionate oxidation at the anode (by e.g. unclassified_c__Bacteroidia), and the stimulations of acetoclastic and direct interspecies electron transfer-dependent CO2-reducing methanogenesis at the cathode (by e.g. Methanothrix). This study provides novel insights into the effect of electrical assistance on ammonia-stressed AD.


Asunto(s)
Amoníaco , Propionatos , Propionatos/metabolismo , Anaerobiosis , Electrones , Metano/metabolismo , Reactores Biológicos
15.
J Transl Med ; 21(1): 886, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057816

RESUMEN

Ovarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal , Neoplasias Ováricas , Humanos , Femenino , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/uso terapéutico , Línea Celular Tumoral , Neoplasias Ováricas/tratamiento farmacológico , Pronóstico , Apoptosis/genética
16.
Pulm Pharmacol Ther ; 83: 102262, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37879430

RESUMEN

PURPOSE: The expression of MUC5AC, a highly prevalent airway mucin, is regulated by stimulatory factors such as oxidative stress. Ganoderic acid D (GAD) activates mitochondrial deacetylase SIRT3. SIRT3 regulates mitochondrial function through deacetylation of mitochondrial proteins, thereby playing a significant role in alleviating oxidative stress-related diseases. Therefore, this study aimed to investigate the mechanisms and rationale underlying the regulation of MUC5AC expression by GAD. METHODS: Human airway epithelial cells (NCI-H292) were exposed to pyocyanin (PCN) to establish an in vitro cell model of airway mucus hypersecretion. The expression of SIRT3, MUC5AC, and NRF2 pathway proteins in cells was assessed. Cellular mitochondrial morphology and oxidative stress markers were analyzed. C57BL/6 mice were induced with Pseudomonas aeruginosa (PA) to establish an in vivo mouse model of airway mucus hypersecretion. The expression of SIRT3 and MUC5AC in the airways was examined. In addition, the differential expression of target genes in the airway epithelial tissues of patients with chronic obstructive pulmonary disease (COPD) was analyzed using publicly available databases. RESULTS: The results revealed a significant upregulation of MUC5AC expression and a significant downregulation of SIRT3 expression in relation to airway mucus hypersecretion. GAD inhibited the overexpression of MUC5AC in PCN-induced NCI-H292 cells and PA-induced mouse airways by upregulating SIRT3. GAD activated the NRF2/GPX4 pathway and inhibited PCN-induced oxidative stress and mitochondrial morphological changes in NCI-H292 cells. However, ML385 inhibited the regulatory effects of GAD on MUC5AC expression. CONCLUSION: The SIRT3 activator GAD downregulated MUC5AC expression, potentially through activation of the NRF2/GPX4 pathway. Accordingly, GAD may be a potential treatment approach for airway mucus hypersecretions.


Asunto(s)
Mucinas , Sirtuina 3 , Humanos , Ratones , Animales , Mucinas/genética , Mucinas/metabolismo , Sirtuina 3/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Endogámicos C57BL , Moco/metabolismo , Mucina 5AC/genética , Mucina 5AC/metabolismo
17.
Int J Mol Sci ; 24(20)2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37894736

RESUMEN

Although it is well recognized that mycosporine-like amino acids (MAAs) are ultraviolet (UV) protective agents that can reduce UV damage, the specific biological mechanism of its role in the skin remains unclear. In this study, we investigated the effect of MAAs extracted from Antarctic diatom Phaeodactylum tricornutum ICE-H on UVB-induced skin damage using a mice model. The MAAs components identified by liquid chromatography-tandem mass spectrometry included 4-deoxygadusol, shinorine, and porphyra-334, which were purified using a Supledean Carboxen1000 solid phase extraction column. The antioxidant activities of these MAA compounds were tested in vitro. For UVB-induced skin photodamage in mice, MAAs alleviated skin swelling and epidermal thickening in this study. We detected the content of reactive oxygen species (ROS), malondialdehyde, and collagen in skin tissue. In addition, quantitative real-time polymerase chain reaction was used to detect nuclear factor-κB (NF-κB), tumor necrosis factor α, interleukin-1ß, cyclooxygenase-2, mitogen activated protein kinase (MAPK) family (extracellular signal-regulated kinase, c-Jun amino-terminal kinase, and p38 kinase), and matrix metalloproteinases. The expression of these cytokines and enzymes is related to inflammatory responses and collagen degradation. In comparison to the model group without MAA treatment, the MAA component decreased the concentration of ROS, the degree of oxidative stress in the skin tissue, and the expression of genes involved in the NF-κB and MAPK pathways. In summary, these MAA components extracted from Phaeodactylum tricornutum ICE-H protected against UVB-induced skin damage by inhibiting ROS generation, relieving skin inflammation, and slowing down collagen degradation, suggesting that these MAA components are effective cosmetic candidate molecules for the protection and therapy of UVB damage.


Asunto(s)
Aminoácidos , Diatomeas , Animales , Ratones , Aminoácidos/química , Diatomeas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Regiones Antárticas , Piel/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Colágeno/farmacología , Rayos Ultravioleta/efectos adversos
18.
BMC Plant Biol ; 23(1): 505, 2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37864141

RESUMEN

BACKGROUND: Non-structural carbohydrates (NSC) play a significant role in plant growth and defense and are an important component of carbon cycling in desert ecosystems. However, regarding global change scenarios, it remains unclear how NSCs in desert plants respond to changing precipitation patterns. [Methods] Three precipitation levels (natural precipitation, a 30% reduction in precipitation, and a 30% increase in precipitation) and two precipitation intervals levels (5 and 15 d) were simulated to study NSC (soluble sugar and starch) responses in the dominant shrub Artemisia ordosica. RESULTS: Precipitation level and interval interact to affect the NSC (both soluble sugar and starch components) content of A. ordosica. The effect of precipitation on NSC content and its components depended on extended precipitation interval. With lower precipitation and extended interval, soluble sugar content in roots increased and starch content decreased, indicating that A. ordosica adapts to external environmental changes by hydrolyzing root starch into soluble sugars. At 5 d interval, lower precipitation increased the NSC content of stems and especially roots. CONCLUSIONS: A. ordosica follows the "preferential allocation principle" to preferentially transport NSC to growing organs, which is an adaptive strategy to maintain a healthy physiological metabolism under drought conditions. The findings help understand the adaptation and survival mechanisms of desert vegetation under the changing precipitation patterns and are important in exploring the impact of carbon cycling in desert systems under global environmental change.


Asunto(s)
Artemisia , Ecosistema , Carbohidratos , Almidón , Azúcares , Carbono
19.
Biomedicines ; 11(9)2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37760803

RESUMEN

Ovarian cancer is the leading cause of gynecological death worldwide, and its poor prognosis and high mortality seriously affect the life of ovarian cancer patients. Runt-related transcription factor 1 (RUNX1) has been widely studied in hematological diseases and plays an important role in the occurrence and development of hematological diseases. In recent years, studies have reported the roles of RUNX1 in solid tumors, including the significantly increased expression of RUNX1 in ovarian cancer. In ovarian cancer, the dysregulation of the RUNX1 signaling pathway has been implicated in tumor progression, metastasis, and response to therapy. At the same time, the decreased expression of RUNX1 in ovarian cancer can significantly improve the sensitivity of clinical chemotherapy and provide theoretical support for the subsequent diagnosis and treatment target of ovarian cancer, providing prognosis and treatment options to patients with ovarian cancer. However, the role of RUNX1 in ovarian cancer remains unclear. Therefore, this article reviews the relationship between RUNX1 and the occurrence and development of ovarian cancer, as well as the closely regulated signaling pathways, to provide some inspiration and theoretical support for future research on RUNX1 in ovarian cancer and other diseases.

20.
Front Oncol ; 13: 1228889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37671047

RESUMEN

Background: FAS-associated death structural domain (FADD) proteins are important proteins that regulate apoptosis and are also involved in many nonapoptotic pathways in tumors. However, how dysregulated FADD affects the development of lung adenocarcinoma (LUAD) remains unknown. Method: Transcriptome profiles and corresponding clinical information of LUAD patients were convened from different databases, and the results were validated by qRT-PCR and cell counting kit-8 using LUAD cell lines. Potential associations between FADD and tumor malignancy, the immune microenvironment, genomic stability, and treatment sensitivity in LUAD patients were revealed by systematic bioinformatics analysis. Results: FADD was significantly overexpressed in LUAD, and patients with higher expression levels of FADD had a worse prognosis and more advanced tumor stage. Functional analysis revealed that elevated expression of FADD was associated with cell cycle dysregulation, angiogenesis, and metabolic disturbances. In addition, overexpression of FADD was associated with a higher infiltration of suppressive immune cells. From a single-cell perspective, cells with lower FADD expression are more active in immune-related pathways. FADD was associated with more genomic mutations, especially TP53. Patients with high FADD expression are more likely to benefit from conventional chemotherapy, while those with low FADD expression are more suitable for immunotherapy. Conclusions: Upregulated FADD is associated with worse prognosis, immune exhaustion, and tumor malignancy in LUAD patients. In addition, FADD can be an efficient indicator for assessing sensitivity to chemotherapy and immunotherapy. Therefore, FADD has the potential to serve as a new target for precision medicine and targeted therapy for LUAD.

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