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1.
PLoS One ; 19(9): e0309978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39302908

RESUMEN

Fritillariae thunbergii Bulbus (FTB) is a traditional Chinese medicine that has been widely cultivated for its expectorant, antitussive, antiasthmatic, antiviral, and anticancer properties. The yield and quality of F. thunbergii are influenced by cultivation conditions, such as the use of fertilizers. However, the optimal type of fertilizers for maximum quality and yield and underlying mechanisms are not clear. We collected F. thunbergii using raw chicken manure (RC), organic fertilizer (OF), and plant ash (PA) as the base fertilizer in Pan'an County, Jinhua City, Zhejiang Province as experimental materials. The combined results of HPLC-ELSD detection and yield statistics showed that the F. thunbergii with OF application was the best, with the content of peimine and peiminine reaching 0.0603% and 0.0502%, respectively. In addition, the yield was 2.70 kg/m2. Transcriptome analysis indicated that up-regulation of the ABA signaling pathway might promote bulb yield. Furthermore, putative key genes responsible for steroidal alkaloid accumulation were identified. These results provided guiding significance for the rational fertilization conditions of F. thunbergii as well as the basis for the exploration of functional genes related to the alkaloid biosynthesis pathway.


Asunto(s)
Fertilizantes , Fritillaria , Fritillaria/genética , Fritillaria/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Cevanas/farmacología , Transcriptoma , Alcaloides , Animales
3.
Chem Biol Interact ; : 111250, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39313106

RESUMEN

BACKGROUND: The incidence of renal cell carcinoma (RCC) is already in the top ten of all types of cancers, with more than 4%. Epigallocatechin gallate (EGCG), a polyphenolic compound extracted from green tea, has been shown to be effective in the treatment of various tumors. However, limited studies have demonstrated the effect of EGCG on RCC and its underlying molecular mechanisms. METHODS: After exposure to gradient concentration ( 0,5,10,20,40,60,80,100 µM ) of EGCG, the cell viability of RCC cells was determined by MTT assay. The migration and invasion abilities of RCC cells were investigated by wound healing and transwell assays. The expression levels of proteins involved in the epithelial-mesenchymal transition (EMT) and autophagy were explored by Western blotting assays. The formation of autophagosome was detected by electron microscope and LC3 puncta assays. Nude mouse xenograft model was used as the model system in vivo. RESULTS: In the present study, EGCG significantly inhibited the migration, invasion and EMT of RCC cells in a concentrated manner. Further exploration of its mechanism indicated that autophagy is involved in EGCG-mediated metastasis inhibition and EMT inhibition of RCC cells. In addition, EGCG could significantly up-regulate the transcription factor EB (TFEB) and promotes its nuclear localization. The incorporation of TFEB into the nucleus enhanced the transcriptional levels of molecules associated with autophagy. TFEB knockdown inhibited EGCG-mediated autophagy activation, metastasis and EMT inhibition in RCC cells. CONCLUSIONS: In conclusion, these findings demonstrate for the first time that EGCG inhibits migration, invasion, and EMT of RCC by activating TFEB-mediated autophagy. Therefore, the combination of EGCG and TFFB activators or EMT inhibitors is expected to be a promising therapeutic strategy for RCC.

4.
Innovation (Camb) ; 5(5): 100691, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39285902

RESUMEN

This paper explores the evolution of geoscientific inquiry, tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence (AI) and data collection techniques. Traditional models, which are grounded in physical and numerical frameworks, provide robust explanations by explicitly reconstructing underlying physical processes. However, their limitations in comprehensively capturing Earth's complexities and uncertainties pose challenges in optimization and real-world applicability. In contrast, contemporary data-driven models, particularly those utilizing machine learning (ML) and deep learning (DL), leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge. ML techniques have shown promise in addressing Earth science-related questions. Nevertheless, challenges such as data scarcity, computational demands, data privacy concerns, and the "black-box" nature of AI models hinder their seamless integration into geoscience. The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm. These models, which incorporate domain knowledge to guide AI methodologies, demonstrate enhanced efficiency and performance with reduced training data requirements. This review provides a comprehensive overview of geoscientific research paradigms, emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience. It examines major methodologies, showcases advances in large-scale models, and discusses the challenges and prospects that will shape the future landscape of AI in geoscience. The paper outlines a dynamic field ripe with possibilities, poised to unlock new understandings of Earth's complexities and further advance geoscience exploration.

5.
Clin Res Hepatol Gastroenterol ; 48(8): 102458, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233138

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with metabolic dysfunction, ranging from hepatic steatosis with or without mild inflammation to nonalcoholic steatohepatitis, which can rapidly progress to liver fibrosis and even liver cancer. In 2023, after several rounds of Delphi surveys, a new consensus recommended renaming NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD). Ninety-nine percent of NAFLD patients meet the new MASLD criteria related to metabolic cardiovascular risk factors under the "multiple parallel hits" of lipotoxicity, insulin resistance (IR), a proinflammatory diet, and an intestinal microbiota disorder, and previous research on NAFLD remains valid. The NLRP3 inflammasome, a well-known member of the pattern recognition receptor (PRR) family, can be activated by danger signals transmitted by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), as well as cytokines involved in immune and inflammatory responses. The activation of the NLRP3 inflammasome pathway by MASLD triggers the production of the inflammatory cytokines IL-1ß and IL-18. In MASLD, while changes in the composition and metabolites of the intestinal microbiota occur, the disrupted intestinal microbiota can also generate the inflammatory cytokines IL-1ß and IL-18 by damaging the intestinal barrier, negatively regulating the liver on the gut-liver axis, and further aggravating MASLD. Therefore, modulating the gut-microbiota-liver axis through the NLRP3 inflammasome may emerge as a novel therapeutic approach for MASLD patients. In this article, we review the evidence regarding the functions of the NLRP3 inflammasome and the intestinal microbiota in MASLD, as well as their interactions in this disease.

6.
Commun Biol ; 7(1): 1106, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251752

RESUMEN

Otopetrin 1 (OTOP1) is a proton-activated channel crucial for animals' perception of sour taste. Despite its significance, the gating mechanism of OTOP1 remains poorly understood. Here, we demonstrate that carvacrol activates the mouse OTOP1 (mOTOP1) channel under neutral and acidic conditions. Functional analysis showed that carvacrol enhances pH fluorescence signals in OTOP1-expressing cells, with reduced efficacy at lower pH levels. Carvacrol selectively activates mOTOP1, while mOTOP2, mOTOP3, and Chelonia mydas OTOP1 (CmOTOP1) are insensitive to carvacrol activation under neutral pH. Through chimera and point mutation experiments, swapping S134 in transmembrane segment 3 (TM3) and T247 in the TM5-6 linker abolished carvacrol activation of mOTOP1 and conferred activation on CmOTOP1, suggesting these two residues are critical for carvacrol sensitivity. These findings highlight TM3 and TM5-6 linker as pivotal gating apparatus of OTOP1 channels and potential docking sites for drug design.


Asunto(s)
Cimenos , Cimenos/farmacología , Animales , Ratones , Activación del Canal Iónico/efectos de los fármacos , Humanos , Células HEK293 , Concentración de Iones de Hidrógeno , Canales Iónicos/metabolismo , Canales Iónicos/genética
7.
Waste Manag ; 190: 55-62, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39276505

RESUMEN

Recovering phosphorus (P) and sulfur (S) from biowaste is a key strategy to address the current P resources shortage and soil S deficiency. Food waste digestate (FWD) contains high contents of P and S, while its direct application is severely limited by available nutrient leaching loss and pollutant exposure. Hydrothermal treatment (HT) is an effective technique for biowaste disposal, enabling detoxification and resource recovery. The study systematically investigated the speciation transformation of P and S in FWD during HT, using chemical extraction and in-situ X-ray absorption near-edge structure (XANES) spectroscopy. The results revealed that up to 98% of P in FWD was enriched in the solid product (hydrochar) after HT, with organic P and labile P being converted into stable Ca-bound forms, predominantly hydroxyapatite. This transformation reduced the risk of P leakage loss compared to untreated FWD. Interestingly, the S speciation evolution exhibited more complexity. The highest S proportion in hydrochar of 73.6% was observed at 140 °C under HT. As the temperature increased from 140 °C to 180 °C, S in the hydrochar gradually dissolved into the liquid phase, attributed to unstable aliphatic compounds (mercaptan) and the sulfides oxidizing to sulfates. Above 180 °C, intermediate oxidation states and sulfates were reduced and formed metal sulfides. These findings have important implications for understanding the viability of HT for FWD disposal and the value-added utilization of FWD.

8.
J Appl Toxicol ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39340181

RESUMEN

Cumulative evidence suggested that nanoplastics (NPs) cause male toxicity, but the mechanisms of which are still misty. Steroidogenesis is a key biological event that responsible for maintaining reproductive health. However, whether dysregulated steroidogenesis is involved in NPs-induced impaired male reproductive function and the underlying mechanism remains unclear. In our study, Balb/c mice were continuously exposed to pristine-NPs or NH2-NPs for 12 weeks, spanning the puberty and adult stage. Upon the long-term NPs treatment, the hypothalamus and testis were subjected to transcriptome and metabolome analysis. And the results demonstrated that both primitive-NPs and NH2-NPs resulted in impaired spermatogenesis and steroidogenesis, as evidenced by a significant reduction in sperm quality, testosterone, FSH, and LH. The expression of genes involved in hypothalamic-pituitary-testis (HPT) axis, such as Kiss-1 and Cyp17a1 that encoded the key steroid hormone synthetase, was also diminished. Furthermore, the phosphatidylcholine and pantothenic acid that mainly enriched in glycerophospholipid metabolism were significantly reduced in the testis. Comprehensive analysis of the transcriptome and metabolome indicated that down-regulated Cyp17a1 was associated with decreased metabolites phosphatidylcholine and pantothenic acid. Overall, we speculate that the disturbed HPT axis induced by long-term NPs contributes to disordered glycerophospholipid metabolism and subsequently impaired steroidogenesis. Our findings deepen the understanding of the action of the mechanism responsible for NPs-induced male reproductive toxicology.

10.
Research (Wash D C) ; 7: 0452, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171118

RESUMEN

Real-time thermal sensing through flexible temperature sensors in extreme environments is critically essential for precisely monitoring chemical reactions, propellant combustions, and metallurgy processes. However, despite their low response speed, most existing thermal sensors and related sensing materials will degrade or even lose their sensing performances at either high or low temperatures. Achieving a microsecond response time over an ultrawide temperature range remains challenging. Here, we design a flexible temperature sensor that employs ultrathin and consecutive Mo1-x W x S2 alloy films constructed via inkjet printing and a thermal annealing strategy. The sensing elements exhibit a broad work range (20 to 823 K on polyimide and 1,073 K on flexible mica) and a record-low response time (about 30 µs). These properties enable the sensors to detect instantaneous temperature variations induced by contact with liquid nitrogen, water droplets, and flames. Furthermore, a thermal sensing array offers the spatial mapping of arbitrary shapes, heat conduction, and cold traces even under bending deformation. This approach paves the way for designing unique sensitive materials and flexible sensors for transient sensing under harsh conditions.

11.
Shanghai Kou Qiang Yi Xue ; 33(3): 269-272, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39104342

RESUMEN

PURPOSE: To investigate the feasibility and effect of free latissimus dorsi myocutaneous flap in the reconstruction of giant head and neck defects. METHODS: Free latissimus dorsi myocutaneous flap on the cadaver was simulated dissected, and measured by Image-Pro Plus 6.0 to assess the feasibility of repairing giant head and neck defects. Between May 2011 and September 2022, seven patients with giant head and neck defects of different causes repaired with the latissimus dorsi myocutaneous flap were retrospectively analyzed. RESULTS: The diameter of the initiating thoracodorsal artery was (4.03±0.56) mm, and the mean lengths of the arteriolar and venous pedicles of the latissimus dorsi myocutaneous flaps obtained from human specimens were (85.5±10.5) mm and (104±4.2) mm, respectively. Among 7 patients, 5 cases had scalp defects, the remaining 2 cases had neck defects. There were no substantial postoperative problems in the donor site, and all seven latissimus dorsi myocutaneous flaps were successfully transplanted. CONCLUSIONS: For the treatment of considerable head and neck deformities, the latissimus dorsi myocutaneous flap is an optimal muscle flap due to its abundance of tissue, enough length of vascular pedicles, and sufficient venous drainage.


Asunto(s)
Colgajo Miocutáneo , Procedimientos de Cirugía Plástica , Músculos Superficiales de la Espalda , Humanos , Músculos Superficiales de la Espalda/trasplante , Colgajo Miocutáneo/trasplante , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Cuello/cirugía , Cuello/anatomía & histología , Cabeza/cirugía , Cabeza/anatomía & histología , Neoplasias de Cabeza y Cuello/cirugía , Cadáver , Cuero Cabelludo/cirugía , Masculino
12.
JMIR Public Health Surveill ; 10: e58821, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39104051

RESUMEN

Background: In the past 10 years, the number of hand, foot, and mouth disease (HFMD) cases reported in Guangzhou, China, has averaged about 60,000 per year. It is necessary to conduct an in-depth analysis to understand the epidemiological pattern and related influencing factors of HFMD in this region. Objective: This study aims to describe the epidemiological characteristics and spatiotemporal distribution of HFMD cases in Guangzhou from 2013 to 2022 and explore the relationship between sociodemographic factors and HFMD incidence. Methods: The data of HFMD cases in Guangzhou come from the Infectious Disease Information Management System of the Guangzhou Center for Disease Control and Prevention. Spatial analysis and space-time scan statistics were used to visualize the spatiotemporal distribution of HFMD cases. Multifactor ordinary minimum regression model, geographically weighted regression, and geographically and temporally weighted regression were used to analyze the influencing factors, including population, economy, education, and medical care. Results: From 2013 to 2022, a total of 599,353 HFMD cases were reported in Guangzhou, with an average annual incidence rate of 403.62/100,000. Children aged 5 years and younger accounted for 93.64% (561,218/599,353) of all cases. HFMD cases showed obvious bimodal distribution characteristics, with the peak period from May to July and the secondary peak period from August to October. HFMDs in Guangzhou exhibited a spatial aggregation trend, with the central urban area showing a pattern of low-low aggregation and the peripheral urban area demonstrating high-high aggregation. High-risk areas showed a dynamic trend of shifting from the west to the east of peripheral urban areas, with coverage first increasing and then decreasing. The geographically and temporally weighted regression model results indicated that population density (ß=-0.016) and average annual income of employees (ß=-0.007) were protective factors for HFMD incidence, while the average number of students in each primary school (ß=1.416) and kindergarten (ß=0.412) was a risk factor. Conclusions: HFMD cases in Guangzhou were mainly infants and young children, and there were obvious differences in time and space. HFMD is highly prevalent in summer and autumn, and peripheral urban areas were identified as high-risk areas. Improving the economic level of peripheral urban areas and reducing the number of students in preschool education institutions are key strategies to controlling HFMD.


Asunto(s)
Enfermedad de Boca, Mano y Pie , Análisis Espacio-Temporal , Enfermedad de Boca, Mano y Pie/epidemiología , China/epidemiología , Humanos , Preescolar , Masculino , Estudios Retrospectivos , Femenino , Lactante , Niño , Incidencia , Adolescente , Factores de Riesgo , Recién Nacido
13.
Materials (Basel) ; 17(16)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39203282

RESUMEN

A high Fe content easily produces Fe-rich phases with a harmful morphology, resulting in a huge detrimental effect on the properties and recycling ability of Al-Si alloys. Therefore, finding ways to effectively transform Fe-rich phases to form a beneficial phase or shape is of great significance. Accordingly, Al-Si-based alloys with Fe contents ranging from 0.1 wt.% to 2.0 wt.% were modified by different Mn additions. Moreover, experiments combined with simulations were utilized to comprehensively analyze the mechanism of Mn on the morphology and microstructural evolution of Fe-rich phases from different perspectives. The current findings determine that adding different Fe contents changes the phase-transition reactions in alloys. Without Mn, and by increasing the Fe content from 0.1 wt.% to 2.0 wt.%, the Fe-rich phases gradually convert from a skeleton-shaped α-Al8Fe2Si (<0.25 wt.%) to ß-Al9Fe2Si2 with a fibrous (0.5 wt.%), needle-like (1.0 wt.%) and plate-like shape without curvatures (2.0 wt.%). The maximum length and mean aspect ratio increase from 12.01 µm to 655.66 µm and from 1.96 to 84.05, while the mean curvature decreases from 8.66 × 10-2 µm-1 to 8.25 × 10-4 µm-1. The addition of 0.35 wt.% Mn promotes a new Chinese-character and petal-shaped α-Al15(FeMn)3Si2, with an atomic ratio of Fe and Mn of 1:1 when the Fe content is lower than 0.5 wt.%, while it transforms to ß-Al15(FeMn)3Si2 with an atomic ratio of 5:1, presenting as a refined plate-like shape with a certain curvature, as the Fe content increases to 2.0 wt.%. Mn alters the phase reactions and increases the threshold of the Fe content required for ß-Al15(FeMn)3Si2, limiting the formation and growth of them simultaneously in time and space. The enrichment of Mn atoms and solute diffusion at the growth front of ß-Al15(FeMn)3Si2, as well as the strong atomic-binding ability, can deflect the growth direction of ß-Al15(FeMn)3Si2 for it to have a certain curvature. Additionally, the enriched Mn atoms easily form α-Al15(FeMn)3Si2 and cause the long ß-Al15(FeMn)3Si2 to be broken and refined to further reduce the damages caused to the alloy's performance. Ultimately, the maximum length and mean aspect ratio can be effectively reduced to 46.2% and 42.0%, respectively, while the mean curvature can be noticeably increased by 3.27 times with the addition of Mn.

14.
Environ Sci Technol ; 58(36): 16186-16195, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39189695

RESUMEN

Metal(loid)s in sewage sludge (SS) are effectively immobilized after pyrolysis. However, the bioavailability and fate of the immobilized metal(loid)s in SS-derived biochar (SSB) following land application remain largely unknown. Here, the speciation and bioavailability evolution of SSB-borne Cr and Zn in soil were systematically investigated by combining pot and field trials and X-ray absorption spectroscopy. Results showed that approximately 58% of Cr existing as Cr(III)-humic complex in SS were transformed into Fe (hydr)oxide-bound Cr(III), while nano-ZnS in SS was transformed into stable ZnS and ferrihydrite-bound species (accounting for over 90% of Zn in SSB) during pyrolysis. All immobilized metal(loid)s, including Cr and Zn, in SSB tended to be slowly remobilized during aging in soil. This study highlighted that SSB acted as a dual role of source and sink of metal(loid)s in soil and posed potential risks by serving a greater role of a metal(loid) source than a sink when applied to uncontaminated soils. Nevertheless, SSB could impede the translocation of metal(loid)s from soil to crop compared to SS, where coexisting elements, including Fe, P, and Zn, played critical roles. These findings provide new insights for understanding the fate of SSB-borne metal(loid)s in soil and assessing the viability of pyrolyzing SS for land application.


Asunto(s)
Cromo , Pirólisis , Aguas del Alcantarillado , Zinc , Aguas del Alcantarillado/química , Zinc/química , Cromo/química , Contaminantes del Suelo/química , Suelo/química , Carbón Orgánico/química
15.
J Control Release ; 373: 399-409, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39033984

RESUMEN

C. neoformans, a life-threatening invasive fungal pathogen, can hijack the pulmonary macrophages as 'Trojan horse', leading to cryptococcal meningitis and recurrence. Combatting these elusive fungi has posed a long-standing challenge. Here, we report an inhaled cascade-targeting drug delivery platform that can sequentially target host cells and intracellular fungi. The delivery system involves encapsulating amphotericin B (AMB) into polymeric particles decorated with AMB, creating a unique surface pattern, denoted as APP@AMB. The surface topology of APP@AMB guides the efficient macrophages internalization and intracellular drugs accumulation. Following endocytosis, the surface-functionalized AMB specifically targets intracellular fungi by binding to ergosterol in the fungal membrane, as demonstrated through co-localization studies using confocal microscopy. Through on-site AMB delivery, APP@AMB displays superior efficacy in eliminating C. neoformans in the lungs and brain compared to free AMB following inhalation in infected mice. Additionally, APP@AMB significantly alleviates the nephrotoxicity associated with free AMB inhalation therapy. Thus, this biocompatible delivery system enabling host cells and intracellular fungi targeting in a cascade manner, provides a new avenue for the therapy of fungal infection.


Asunto(s)
Anfotericina B , Antifúngicos , Criptococosis , Cryptococcus neoformans , Sistemas de Liberación de Medicamentos , Cryptococcus neoformans/efectos de los fármacos , Animales , Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Criptococosis/tratamiento farmacológico , Ratones , Polímeros/química , Polímeros/administración & dosificación , Pulmón/metabolismo , Pulmón/microbiología , Células RAW 264.7 , Ratones Endogámicos BALB C , Administración por Inhalación , Femenino , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos
16.
ACS Nano ; 18(32): 21411-21432, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39079092

RESUMEN

Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.


Asunto(s)
Antioxidantes , Animales , Conejos , Antioxidantes/farmacología , Antioxidantes/química , Adherencias Tisulares/prevención & control , Espacio Epidural/patología , Espacio Epidural/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Cisteína/química , Cisteína/farmacología , Humanos , Ratones , Adhesivos/química , Adhesivos/farmacología , Masculino
17.
Chem Biol Interact ; 400: 111158, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39033796

RESUMEN

Multi-walled carbon nanotube (MWCNT) induced respiratory toxicity has become a growing concern, with ferroptosis emerging as a novel mechanism implicated in various respiratory diseases. However, whether ferroptosis is involved in MWCNT-elicited lung injury and the underlying molecular mechanisms warrant further exploration. In this study, we found that MWCNT-induced ferroptosis is autophagy-dependent, contributing to its cellular toxicity. Inhibiting of autophagy by pharmacological inhibitors 3-MA or ATG5 gene knockdown significantly attenuated MWCNT-induced ferroptosis, concomitant with rescued mitochondrial biogenesis. Rapamycin, the autophagy agonist, exacerbated the mitochondrial damage and MWCNT-induced ferroptosis. Moreover, lentivirus-mediated overexpression of PGC-1α inhibited ferroptosis, while inhibition of PGC-1α aggravated ferroptosis. In summary, our study unveils ferroptosis as a novel mechanism underlying MWCNT-induced respiratory toxicity, with autophagy promoting MWCNT-induced ferroptosis by hindering PGC-1α-dependent mitochondrial biogenesis.


Asunto(s)
Autofagia , Ferroptosis , Pulmón , Nanotubos de Carbono , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Nanotubos de Carbono/toxicidad , Ferroptosis/efectos de los fármacos , Autofagia/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 , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Pulmón/citología , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Biogénesis de Organelos , Proteína 5 Relacionada con la Autofagia/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Animales , Sirolimus/farmacología , Ratones , Línea Celular
19.
Zhen Ci Yan Jiu ; 49(7): 700-706, 2024 Jul 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39020488

RESUMEN

OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 grades:no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.


Asunto(s)
Moxibustión , Náusea , Neoplasias , Vómitos , Zingiber officinale , Humanos , Masculino , Persona de Mediana Edad , Femenino , Zingiber officinale/química , Adulto , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Anciano , Náusea/terapia , Náusea/etiología , Náusea/prevención & control , Vómitos/terapia , Puntos de Acupuntura , Adulto Joven , Terapia por Acupuntura , Antineoplásicos/efectos adversos , Tracto Gastrointestinal/fisiopatología
20.
Artículo en Inglés | MEDLINE | ID: mdl-39012736

RESUMEN

Remote noncontact respiratory rate estimation by facial visual information has great research significance, providing valuable priors for health monitoring, clinical diagnosis, and anti-fraud. However, existing studies suffer from disturbances in epidermal specular reflections induced by head movements and facial expressions. Furthermore, diffuse reflections of light in the skin-colored subcutaneous tissue caused by multiple time-varying physiological signals independent of breathing are entangled with the intention of the respiratory process, leading to confusion in current research. To address these issues, this article proposes a novel network for natural light video-based remote respiration estimation. Specifically, our model consists of a two-stage architecture that progressively implements vital measurements. The first stage adopts an encoder-decoder structure to recharacterize the facial motion frame differences of the input video based on the gradient binary state of the respiratory signal during inspiration and expiration. Then, the obtained generative mapping, which is disentangled from various time-varying interferences and is only linearly related to the respiratory state, is combined with the facial appearance in the second stage. To further improve the robustness of our algorithm, we design a targeted long-term temporal attention module and embed it between the two stages to enhance the network's ability to model the breathing cycle that occupies ultra many frames and to mine hidden timing change clues. We train and validate the proposed network on a series of publicly available respiration estimation datasets, and the experimental results demonstrate its competitiveness against the state-of-the-art breathing and physiological prediction frameworks.

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