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1.
Gene ; 932: 148908, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39218414

RESUMEN

BACKGROUND: Although progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. METHODS: We were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. RESULTS: A total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. CONCLUSION: We proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Simulación por Computador , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Perfilación de la Expresión Génica/métodos , Línea Celular Tumoral , Persona de Mediana Edad
2.
Biomaterials ; 313: 122776, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39236629

RESUMEN

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.


Asunto(s)
Células Dendríticas , Hidrogeles , Melanoma , Cicatrización de Heridas , Hidrogeles/química , Animales , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Melanoma/terapia , Melanoma/patología , Cicatrización de Heridas/efectos de los fármacos , Humanos , Recurrencia Local de Neoplasia/prevención & control , Ratones Endogámicos C57BL , Antiinfecciosos/uso terapéutico , Antiinfecciosos/farmacología , Ratones , Línea Celular Tumoral , Femenino
3.
J Environ Sci (China) ; 149: 465-475, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39181659

RESUMEN

VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources. Results indicated that the TVOCs (total VOCs) concentration was (96.7 ± 63.4 µg/m3), with alkanes exhibiting the highest concentration of (36.1 ± 26.4 µg/m3), followed by OVOCs (16.4 ± 14.4 µg/m3). The key active components were alkenes and aromatics, among which xylene, propylene, toluene, propionaldehyde, acetaldehyde, ethylene, and styrene played crucial roles as reactive species. The sources derived from PMF analysis encompassed vehicle emissions, solvent and coating sources, combustion sources, industrial emissions sources, as well as plant sources, the contribution of which were 37.80%, 27.93%, 16.57%, 15.24%, and 2.46%, respectively. Hence, reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.


Asunto(s)
Contaminantes Atmosféricos , Monitoreo del Ambiente , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Contaminantes Atmosféricos/análisis , China , Emisiones de Vehículos/análisis , Ciudades , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis
4.
J Ethnopharmacol ; 336: 118751, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39214192

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.


Asunto(s)
Cardiotoxicidad , Metabolómica , Transcriptoma , Animales , Metabolómica/métodos , Masculino , Transcriptoma/efectos de los fármacos , Ratas , Bufanólidos/toxicidad , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Farmacología en Red , Cápsulas , Transducción de Señal/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Anuros
5.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4118-4127, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307744

RESUMEN

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis(AS) and decipher the underlying mechanism. The mouse model of AS was established by feeding with a high-fat diet for 12 weeks. The 50 successfully modeled mice with the apolipoprotein E knockout(ApoE~(-/-)) were assigned by the random number table method into 5 groups(n=10): model, low-, medium-, and high-dose(130.54, 261.08, 522.16 mg·kg~(-1), respectively) Zhuyu Pills, and atorvastatin calcium(10.40 mg·kg~(-1)). Ten C57BL/6J mice were selected as the blank group. The blank group and model group were administrated with an equal volume of normal saline, and other groups were administrated with corresponding drugs once a day for 12 weeks. At the end of drug intervention, hematoxylin-eosin(HE) staining was employed to observe the pathological changes of fat in the aorta, liver, and epididymis of mice, and the proportion of aortic plaque area, fat area in epididymis, and nonalcoholic fatty liver disease activity score(NAS) were calculated. Lipid and collagen deposition in the aorta was observed by oil red O staining and Masson staining, respectively, and the proportions of lipid and collagen deposition areas were calculated. The serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), and iron ion were measured by colorimetry. The expression of cyclooxygenase 2(COX2), ferritin heavy chain 1(FTH1), cystine/glutamate reverse transporter solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4) in the aorta was detected by the immunofluorescence assay. The level of tumor protein 53(p53) in the aorta was detected by immunohistochemistry. The protein levels of p53 and SLC7A11 in the aorta were determined by Western blot. The mRNA levels of p53, SLC7A11, GPX4, FTH1, prostaglandin G/H synthase 2(PTGS2), and reduced nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1) in mouse aorta were determined by real-time PCR. The results showed that compared with the blank group, the model group showcased enlarged aortic plaque area, increased collagen fiber deposition, liver lipid deposition, and lipid droplets, and enlarged epididymal adipocytes. In addition, the modeling elevated the levels of iron ion and MDA and lowered the levels of SOD and GSH-Px in the serum, promoted the expression of p53 and COX2, down-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and up-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium reduced the aortic plaque area, collagen deposition, liver lipid deposition, lipid droplets, and epididymal adipocyte volume, lowered the levels of iron ion and MDA and elevated the levels of SOD and GSH-Px in the serum, inhibited the expression of p53 and COX2, up-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and down-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. In conclusion, Zhuyu Pills exert definite therapeutic effect on aortic plaque in AS mice by regulating the p53/SLC7A11 signaling pathway to alleviate oxidative damage and inhibit ferroptosis.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Aterosclerosis , Medicamentos Herbarios Chinos , Ferroptosis , Estrés Oxidativo , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Humanos , Masculino , Ratones , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Aterosclerosis/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Ferroptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética
6.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4488-4498, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307785

RESUMEN

This study aims to explore the potential mechanism of action of Trichosanthis Pericarpium(TP) in improving coronary heart disease(CHD) based on a CHD rat model and metabolomics. The rat model of CHD was built by subcutaneous injection of high-fat diet combined with isoprenaline hydrochloride(ISO). To compare the expression level of lactate dehydrogenase, cardiac troponin Ⅰ(cTnⅠ), creatine kinase-MB(CK-MB), creatine kinase(CK), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß),interleukin-6(IL-16), hypersensitive C-reactive protein(hs-CRP) in serum and cardiac pathological changes of model animals after administration of TP, LTQ-Orbitrap-MS analysis was combined with principal component analysis. The effect of TP on endogenous metabolites in the feces of CHD rats was studied. In addition, biomarkers were identified using the HMDB database and metabolic pathway enrichment analysis was performed using the MetaboAnalyst online pathway enrichment tool. The content of bile acid was further determined in the feces and serum of different groups of rats. Compared with blank group, the myocardial injury markers(CK,LDH, cTnⅠ, CK-MB) and inflammatory factors(TNF-α, IL-1ß, IL-6, hs-CRP) in serum of CHD rats were significantly increased.Myocardial injury and inflammatory infiltration in CHD rats were significantly improved by TP extract. The primary bile acid biosynthetic metabolism pathway was enriched by non-targeted metabolome analysis. The levels of total bile acid, primary bile acid,secondary bile acid, and unconjugated bile acids in the feces of CHD rats were significantly lower than those of control rats. Fecal excretion of total bile acid, primary bile acid, and unconjugated bile acid was significantly improved by TP extract. The levels of total bile acid, primary bile acid, secondary bile acid, and unconjugated bile acids in the serum of CHD rats were significantly higher than those of control rats. Circulating blood levels of total bile acids, primary bile acids, secondary bile acids, and unconjugated bile acids were significantly reduced by TP extract. Increasing fecal excretion of bile acid and decreasing the level of bile acid in blood circulation can improve CHD, and maintaining proper bile acid metabolism is one of the mechanisms of TP to improve CHD.


Asunto(s)
Ácidos y Sales Biliares , Enfermedad Coronaria , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Animales , Ratas , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/metabolismo , Ácidos y Sales Biliares/metabolismo , Masculino , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Interleucina-6/metabolismo , Interleucina-6/genética
7.
Int J Ophthalmol ; 17(9): 1675-1680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296571

RESUMEN

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P<0.01). No serious complications occurred in all cases. CONCLUSION: The new surgery technique (covering CSL) has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study. And it can effectively improve the visual function of patients. This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

8.
Chem Sci ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39296994

RESUMEN

An unusual cascade C-H activation, vinylation and 6π-electrocyclization of 2-pyridyl aldimines with vinyl bromides/triflates was achieved using catalysis with a unique CCC pincer NHC-Ru(iii) complex (Cat B). This reaction was found to enable a rapid and diverse synthesis of polycyclic 4H-pyrido[1,2-a]pyrimidine derivatives in mostly good to high yields, and with a broad substrate scope. A mechanistic study suggested the formation of a semi-opened Ru(iii) intermediate chelating/activating the aldimine, and the occurrence of single-electron transfer (SET) to generate a vinyl radical, followed by vinylation and then an intramolecular 6π-electrocyclization of 1N,3N-hexatrene to form the product. This protocol provides a convenient approach for preparing and seeking new drug candidates.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39298300

RESUMEN

In recent years, many single hyperspectral image super-resolution methods have emerged to enhance the spatial resolution of hyperspectral images without hardware modification. However, existing methods typically face two significant challenges. First, they struggle to handle the high-dimensional nature of hyperspectral data, which often results in high computational complexity and inefficient information utilization. Second, they have not fully leveraged the abundant spectral information in hyperspectral images. To address these challenges, we propose a novel hyperspectral super-resolution network named SNLSR, which transfers the super-resolution problem into the abundance domain. Our SNLSR leverages a spatial preserve decomposition network to estimate the abundance representations of the input hyperspectral image. Notably, the network acknowledges and utilizes the commonly overlooked spatial correlations of hyperspectral images, leading to better reconstruction performance. Then, the estimated low-resolution abundance is super-resolved through a spatial spectral attention network, where the informative features from both spatial and spectral domains are fully exploited. Considering that the hyperspectral image is highly spectrally correlated, we customize a spectral-wise non-local attention module to mine similar pixels along spectral dimension for high-frequency detail recovery. Extensive experiments demonstrate the superiority of our method over other state-of-the-art methods both visually and metrically.

10.
ACS Nano ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301666

RESUMEN

Lithiation, a process of inserting lithium ions into a host material, is revolutionizing nanomaterials synthesis and structural engineering as well as enhancing their performance across emerging applications, particularly valuable for large-scale synthesis of high-quality low-dimensional nanomaterials. Through a systematic investigation of the synthetic strategies and structural changes induced by lithiation, this review aims to offer a comprehensive understanding of the development, potential, and challenges associated with this promising approach. First, the basic principles of lithiation/delithiation processes will be introduced. Then, the recent advancements in the lithiation-induced structure changes of nanomaterials, such as morphology tuning, phase transition, defect generation, etc., will be stressed, emphasizing the importance of lithiation in structural modulation of nanomaterials. With the tunable structures induced by the lithiation, the properties and performance in electrochemical, photochemical, electronic devices, bioapplications, etc. will be discussed, followed by outlining the current challenges and perspectives in this research area.

11.
Can J Gastroenterol Hepatol ; 2024: 5667986, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39314528

RESUMEN

Background: This study aimed to examine whether repeated measurements on noninvasive fibrosis scores during follow-up improve long-term nonalcoholic fatty liver disease (NAFLD) outcome prediction. Methods: A cohort study of 2,280 NAFLD patients diagnosed at the Seoul National University Hospital from 2001 to 2015 was conducted. Multivariable Cox regression models with baseline and designated time-point measurements of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were used to assess the association between these scores and overall mortality, liver-related outcomes, and cardiovascular events. Results: Higher baseline NFS (high versus low probability for advanced fibrosis groups) was associated with higher risk of mortality (adjusted hazard ratio (aHR), (95% confidence interval (CI)), 2.80, [1.39-5.63]) and liver-related outcomes (3.70, [1.27-10.78]). Similar findings were observed for the association of baseline FIB-4 with mortality (2.49, [1.46-4.24]) and liver-related outcomes (11.50, [6.17-21.44]). In models considering designated time-point measurements of the scores, stronger associations were noted. For NFS, a higher time-point measurement was associated with a significantly higher risk of mortality (3.01, [1.65-5.49]) and liver-related outcomes (6.69, [2.62-17.06]). For FIB-4, higher time-point measurements were associated with significantly higher mortality (3.01, [1.88-4.82]) and liver-related outcomes (13.26, [6.89-25.53]). An annual increase in FIB-4 (2.70, [1.79-4.05]) or NFS (4.68, [1.52-14.44]) was associated with an increased risk of liver-related outcomes. No association between NFS/FIB-4 and risk of cardiovascular events was observed in both models. Conclusions: Higher aHRs describing the associations of FIB-4/NFS with overall mortality and liver-related outcomes were observed in the models that included designated time-point measurements of the scores. In addition to the baseline measurement, a routine monitoring on these scores may be important in predicting prognosis of NAFLD patients.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Valor Predictivo de las Pruebas , Humanos , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Masculino , Femenino , República de Corea/epidemiología , Persona de Mediana Edad , Pronóstico , Adulto , Cirrosis Hepática/mortalidad , Índice de Severidad de la Enfermedad , Modelos de Riesgos Proporcionales , Factores de Tiempo , Estudios de Cohortes , Enfermedades Cardiovasculares/mortalidad , Estudios de Seguimiento
12.
Mar Environ Res ; 202: 106754, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39317087

RESUMEN

This study investigated the impacts of sulfamethazine (SMZ) and oxytetracycline (OTC) antibiotics on the marine microalgae Nitzschia closterium and its release of volatile halocarbons (VHCs), which contribute to ozone depletion and climate change. High concentrations of SMZ and OTC suppressed cell density, reduced chlorophyll a content, and hindered Fv/Fm elevation in N. closterium, indicating its growth was inhibited. The exposure of N. closterium to antibiotics led to increased reactive oxygen species (ROS), reduced soluble protein content, and heightened catalase (CAT) activity, indicative of increased oxidative stress. This stress increased the release of three VHCs (CHBrCl2, CHBr2Cl, and CHBr3). Ship-borne experiments showed that high phytoplankton biomass was linked to high VHC release. Notably, the production and release of VHCs were significantly higher in the high-concentration antibiotic group (100 µg/L) than the low-concentration group (0.1 µg/L). These findings suggested that antibiotics induce excess ROS in algal cells, stimulating VHC production and release.

13.
J Exp Bot ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303008

RESUMEN

Anthocyanins, a group of flavonoids, play diverse roles in plant growth and environmental adaptation. The biosynthesis and accumulation of anthocyanin are regulated by environmental cues, such as high light. However, the precise mechanism underlying anthocyanin biosynthesis under high light conditions remains largely unclear. Here, we report that the R3-MYB repressor MYB-LIKE 2 (MYBL2) negatively regulates high light-induced anthocyanin biosynthesis by repressing two R2R3-MYB activators, PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) and PAP2, which are core components of the MYB-bHLH-WD40 (MBW) complex. We found that MYBL2 interacts with PAP1/2 and reduces their transcriptional activation activities, thus disrupting the expression of key genes involved in anthocyanin biosynthesis, such as DIHYDROFLAVONOL 4-REDUCTASE (DFR) and TRANSPARENT TESTA 19 (TT19). Additionally, MYBL2 attenuates the transcriptional activation of PAP1 on its own expression, but not PAP2. Conversely, PAP1 collaborates with TT8, a bHLH member of the MBW complex, to activate MYBL2 transcription when excessive anthocyanins are accumulated. Taken together, our findings reveal a negative feedback regulatory module composed of MYBL2 and PAP1 that fine-tunes high light-induced anthocyanin biosynthesis through modulating MBW complex assembly.

14.
Adv Sci (Weinh) ; : e2404753, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303219

RESUMEN

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH2, are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondrial SIRT3 is reduced in cisplatin-treated mouse kidneys and HK-2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin-caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction-evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin-induced AKI.

15.
J Biol Chem ; : 107783, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303913

RESUMEN

N6-Methyladenosine (m6A) is the most prevalent mRNA modification. Its biological function primarily relies on its "Reader" protein, such as YTHDC2. Previous studies have shown that YTHDC2 downregulation is a pro-carcinogenic phenomenon in lung adenocarcinoma (LUAD). However, further investigation is needed to understand the molecular mechanisms of downstream genes and the associated biological phenomena following YTHDC2 downregulation. Here, we found that YTHDC2 knockout upregulated exosome content in LUAD. Following YTHDC2 knockout, the mRNA levels of OAS family members (OASs) and IFIT family members (IFITs) also decreased; and inhibition of OASs and IFITs could promote exosome content. Several m6A modification sites on the NT domain of OASs and the TPR12 domain of IFITs were found to increase the stability of OASs and IFITs in a YTHDC2-dependent manner. OASs and IFITs affected exosome content through target genes including RAB5A, RAB7 and RAB11A, and three arginine (R) amino acids on IFITs were critical for combination IFITs with targeted RAB mRNAs and subsequent degradation. Simultaneously, OASs degraded targeted RABs through RNAseL. Additionally, mutual bindings between OASs and IFITs were critical for their target gene degradation. Collectively, the above findings might provide a theoretical basis for the treatment of LUAD patients with low YTHDC2 expression.

16.
J Control Release ; 375: 627-642, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39284525

RESUMEN

Methicillin-Resistant Staphylococcus aureus forming into biofilms can trigger chronic inflammation and disrupt skin wound healing processes. Prolonged and excessive use of antibiotics can expedite the development of resistance, primarily because of their limited ability to penetrate microbial membranes and biofilms, especially antibiotics with intracellular drug targets. Herein, we devise a strategy in which virus-inspired nanoparticles control the release of antibiotics through rapid penetration into both bacterial cells and biofilms, thereby combating antimicrobial-resistant infections and promoting skin wound healing. Lipid-based nanoparticles based on stearamine and cholesterol were designed to mimic viral highly ordered nanostructures. To mimic the arginine-rich fragments in viral protein transduction domains, the primary amines on the surface of the lipid-based nanoparticles were exchanged by guanidine segments. Levofloxacin, an antibiotic that inhibits DNA replication, was chosen as the model drug to be incorporated into nanoparticles. Hyaluronic acid was coated on the surface of nanoparticles acting as a capping agent to achieve bacterial-specific degradation and guanidine explosion in the bacterial microenvironment. Our virus-inspired nanoparticles displayed long-acting antibacterial effects and powerful biofilm elimination to overcome antimicrobial-resistant infections and promote skin wound healing. This work demonstrates the ability of virus-inspired nanoparticles to achieve a dual penetration of microbial cell membranes and biofilm structures to address antimicrobial-resistant infections and trigger skin wound healing.

17.
Antonie Van Leeuwenhoek ; 118(1): 8, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305338

RESUMEN

A novel bacterial strain, designated DW002T, was isolated from the sea ice of Cape Evans, McMurdo Sound, Antarctica. Cells of the strain were Gram-negative, obligate anaerobic, motile, non-flagellated, and short rod-shaped. The strain DW002T grew at 4-32 â„ƒ (optimum at 22-28 â„ƒ) and thrived best at pH 7.0, NaCl concentration of 2.5% (w/v). The predominant isoprenoid quinone of strain DW002T was menaquinone-7 (MK-7). The major fatty acids (> 10%) of DW002T were iso-C15:0, anteiso-C15:0 and iso-C17:1ω9c. The predominant polar lipids of strain DW002T contained two phosphatidylethanolamines, one unidentified glycolipid, one unidentified aminolipid and four unidentified lipids. The DNA G + C content of the strain DW002T was 34.8%. Strain DW002T encoded 237 carbohydrate-active enzymes. The strain DW002T had genes associated with dissimilatory nitrate reduction and assimilatory sulfate reduction metabolic pathways. Based on distinct physiological, chemotaxonomic, genome analysis and phylogenetic differences compared to other members of the phylogenetically related genera in the family Marinifilaceae, strain DW002T is proposed to represent a novel genus within the family. Therefore, the name Paralabilibaculum antarcticum gen. nov., sp. nov. is proposed. The type strain is DW002T (=KCTC 25274T=MCCC 1K06067T).


Asunto(s)
Composición de Base , ADN Bacteriano , Ácidos Grasos , Cubierta de Hielo , Filogenia , ARN Ribosómico 16S , Regiones Antárticas , ARN Ribosómico 16S/genética , Ácidos Grasos/metabolismo , Cubierta de Hielo/microbiología , ADN Bacteriano/genética , Anaerobiosis , Técnicas de Tipificación Bacteriana , Fosfolípidos/análisis
18.
West J Emerg Med ; 25(5): 725-734, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39319803

RESUMEN

Introduction: Eye emergencies make up nearly 3% of US emergency department (ED) visits. While emergency physicians (EP) should diagnose and treat these ophthalmologic emergencies, many trainees report limited ocular exposure and insufficient training throughout their residency to confidently conduct a thorough slit-lamp exam. Methods: We created an interdisciplinary, simulation-based mastery learning (SBML) curriculum to teach emergency attending physicians how to operate the slit lamp with multimodal learning methodology at a tertiary academic center. The EPs first demonstrate their initial slit-lamp competency with a 20-item checklist, and they then review the necessary curricular content to pass their independent readiness test before completing their in-person teaching and demonstration session with an ophthalmology attending to demonstrate procedural mastery (minimal passing score >90%). Results: Fifteen EPs were enrolled; all completed the final exam of the curriculum. The pre- and post-curriculum checklist scores increased by an average of seven points (P = .002); 86.7% of EPs felt confident in completing a slit-lamp exam after the curriculum, compared to 20% at the beginning. Five of 15 reported teaching learners within the two-month post-curricular period, ranging from 5-30 students. The hands-on teaching was the most positively reviewed element of the curriculum. Conclusion: The SBML program successfully trained EPs on performing a comprehensive slit-lamp exam with promising results of downstream education to junior learners. We encourage other institutions to leverage SBML as a teaching modality for procedural-based training and advocate cross-discipline education initiatives.


Asunto(s)
Competencia Clínica , Curriculum , Medicina de Emergencia , Servicio de Urgencia en Hospital , Humanos , Medicina de Emergencia/educación , Oftalmología/educación , Evaluación Educacional , Internado y Residencia , Microscopía con Lámpara de Hendidura , Entrenamiento Simulado/métodos , Lámpara de Hendidura
19.
Nanomicro Lett ; 17(1): 6, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39304540

RESUMEN

Catalyst-support interaction plays a crucial role in improving the catalytic activity of oxygen evolution reaction (OER). Here we modulate the catalyst-support interaction in polyaniline-supported Ni3Fe oxide (Ni3Fe oxide/PANI) with a robust hetero-interface, which significantly improves oxygen evolution activities with an overpotential of 270 mV at 10 mA cm-2 and specific activity of 2.08 mA cmECSA-2 at overpotential of 300 mV, 3.84-fold that of Ni3Fe oxide. It is revealed that the catalyst-support interaction between Ni3Fe oxide and PANI support enhances the Ni-O covalency via the interfacial Ni-N bond, thus promoting the charge and mass transfer on Ni3Fe oxide. Considering the excellent activity and stability, rechargeable Zn-air batteries with optimum Ni3Fe oxide/PANI are assembled, delivering a low charge voltage of 1.95 V to cycle for 400 h at 10 mA cm-2. The regulation of the effect of catalyst-support interaction on catalytic activity provides new possibilities for the future design of highly efficient OER catalysts.

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