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1.
World Neurosurg ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39094940

RESUMEN

BACKGROUND: There is currently no established criterion for determining when interventional treatment is necessary and what strategy is appropriate for basilar artery (BA) aneurysms. Through this study, we aimed to propose an algorithm that can effectively determine the optimal endovascular treatment (EVT) option for BA aneurysms. METHODS: We enrolled patients with BA aneurysms from June 2016 to December 2022 and performed procedures based on the algorithm. The analysis included demographic, clinical, and aneurysmal characteristics, procedural details, complications, angiographic outcomes, and clinical outcomes. RESULTS: This study included 124 patients (mean age 55.0 years) with a BA aneurysm who underwent EVT. Of these, 21 aneurysms were treated in the setting of subarachnoid hemorrhage (SAH). The majority of aneurysms were located at the basilar apex (74), followed by the basilar trunk (30) and vertebrobasilar junction (20). Coiling was used in 18.5% of cases, while stent-assisted coiling embolization was chosen for 58.9%. Overlapping stents were used in 12.9%, flow diverter (FD) implantation in 3.2%, Y/T stent techniques in 4.8%, and stent adjunctive coiling with unilateral vertebral artery (VA) occlusion in only 1.6%. Procedure-related complications occurred in 15 patients (12.1%). Patients had a modified Rankin Scale(mRS) score of 0.74±1.62; 98 (86.7%) had good prognosis with mRS scores ranging from 0 to 2 at the last follow-up. DSA was performed on 105 (84.7%) patients revealing that 101 (81.5%) achieved complete or near-complete occlusion. CONCLUSIONS: The endovascular treatment criteria for BA aneurysms depended on the multi-characteristics was safe and effective. However, further evidence is needed from large cohort studies.

2.
Biomed Pharmacother ; 177: 117087, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964178

RESUMEN

Thirteen previously undescribed lindenane sesquiterpenoid dimers (LSDs), named chlorahololides G-S (1-13), were isolated from the whole plants of Chloranthus holostegius var. shimianensis, along with ten known analogues (14-23). The structures and absolute configurations of compounds 1-13 were elucidated through comprehensive spectroscopic analysis, NMR and electronic circular dichroism (ECD) calculations, and X-ray single-crystal diffraction. Chlorahololide G (1) represents the first instance of LSDs formed via a C-15-C-9' carbon-carbon single bond, whose plausible biosynthetic pathway was also proposed. Chlorahololides I and J (3 and 4) were deduced to be rare 8,9-seco and 9-deoxy LSDs with C-11-C-7' carbon-carbon bond, respectively. The inhibitory activity against NLRP3 inflammasome activation was evaluated for all isolates, with six compounds (5, 7, 8, 17, 22, and 23) exhibiting significant effects, and IC50 values ranging from 2.99 to 8.73 µM. Additionally, a preliminary structure-activity relationship analysis regarding their inhibition of NLRP3 inflammasome activation was summarized. Compound 17 exhibited dose-dependent inhibition of nigericin-induced pyroptosis in J774A.1 cells. Molecular docking studies suggested a strong interaction between compound 17 and NLRP3.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Sesquiterpenos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/química , Animales , Ratones , Simulación del Acoplamiento Molecular , Dimerización , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación
3.
J Med Chem ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082833

RESUMEN

Endometrial cancer (EC) is the most common cancer of the female reproductive tract, and there is an urgent need to develop new candidate drugs with good efficacy and safety to improve the survival rate and life quality of EC patients. Herein, a series of new azaphenothiazine derivatives were designed and synthesized and their anti-EC activities were evaluated. Among them, compound 33 showed excellent antiproliferative activities against both progesterone-sensitive ISK cells and progesterone-resistant KLE cells. Moreover, 33 could significantly inhibit colony formation and migration of EC cells and induce cell apoptosis. Remarkably, 33 significantly suppressed KLE xenograft tumor growth without influencing body weights or key organs. In addition, 33 exhibited good pharmacokinetic properties and low extrapyramidal side effects. Mechanism research indicated that 33 reduced Ca2+ levels in mitochondria by targeting GRP75 and disrupting its interaction with IP3R. Overall, 33 showed promising potential as an anti-EC candidate agent.

4.
Cell Commun Signal ; 22(1): 357, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987851

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.


Asunto(s)
Senescencia Celular , Células Epiteliales , Exosomas , Túbulos Renales , Macrófagos , MicroARNs , Telómero , MicroARNs/genética , MicroARNs/metabolismo , Senescencia Celular/genética , Exosomas/metabolismo , Exosomas/genética , Animales , Células Epiteliales/metabolismo , Células Epiteliales/patología , Macrófagos/metabolismo , Túbulos Renales/patología , Túbulos Renales/metabolismo , Ratones , Telómero/genética , Telómero/metabolismo , Humanos , Ratones Endogámicos C57BL , Masculino , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Fibrosis/genética , Angiotensina II
5.
Talanta ; 278: 126496, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38996563

RESUMEN

Dopamine is an important neurotransmitter in the body and closely related to many neurodegenerative diseases. Therefore, the detection of dopamine is of great significance for the diagnosis and treatment of diseases, screening of drugs and unraveling of relevant pathogenic mechanisms. However, the low concentration of dopamine in the body and the complexity of the matrix make the accurate detection of dopamine challenging. Herein, an electrochemical sensor is constructed based on ternary nanocomposites consisting of one-dimensional Pt nanowires, two-dimensional MXene nanosheets, and three-dimensional porous carbon. The Pt nanowires exhibit excellent catalytic activity due to the abundant grain boundaries and highly undercoordinated atoms; MXene nanosheets not only facilitate the growth of Pt nanowires, but also enhance the electrical conductivity and hydrophilicity; and the porous carbon helps induce significant adsorption of dopamine on the electrode surface. In electrochemical tests, the ternary nanocomposite-based sensor achieves an ultra-sensitive detection of dopamine (S/N = 3) with a low limit of detection (LOD) of 28 nM, satisfactory selectivity and excellent stability. Furthermore, the sensor can be used for the detection of dopamine in serum and in situ monitoring of dopamine release from PC12 cells. Such a highly sensitive nanocomposite sensor can be exploited for in situ monitoring of important neurotransmitters at the cellular level, which is of great significance for related drug screening and mechanistic studies.


Asunto(s)
Carbono , Dopamina , Técnicas Electroquímicas , Nanocompuestos , Nanocables , Platino (Metal) , Dopamina/análisis , Dopamina/sangre , Dopamina/química , Platino (Metal)/química , Células PC12 , Nanocables/química , Nanocompuestos/química , Animales , Carbono/química , Ratas , Porosidad , Técnicas Electroquímicas/métodos , Neuronas/metabolismo , Límite de Detección , Electrodos
6.
Int Immunopharmacol ; 139: 112745, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39059099

RESUMEN

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment.


Asunto(s)
Lesión Renal Aguda , Ratones Endogámicos C57BL , Ratones Noqueados , Necroptosis , Receptores de Bombesina , Animales , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Humanos , Necroptosis/efectos de los fármacos , Ratones , Masculino , Línea Celular , Receptores de Bombesina/metabolismo , Receptores de Bombesina/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
7.
Gene ; 927: 148758, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38977109

RESUMEN

The gut microbiota is a treasure trove of carbohydrate-active enzymes (CAZymes). To explore novel and efficient CAZymes, we analyzed the 4,142 metagenome-assembled genomes (MAGs) of the horse gut microbiota and found the MAG117.bin13 genome (Bacteroides fragilis) contains the highest number of polysaccharide utilisation loci sites (PULs), indicating its high capability for carbohydrate degradation. Bioinformatics analysis indicate that the PULs region of the MAG117.bin13 genome encodes many hypothetical proteins, which are important sources for exploring novel CAZymes. Interestingly, we discovered a hypothetical protein (595 amino acids). This protein exhibits potential CAZymes activity and has a lower similarity to CAZymes, we named it BfLac2275. We purified the protein using prokaryotic expression technology and studied its enzymatic function. The hydrolysis experiment of the polysaccharide substrate showed that the BfLac2275 protein has the ability to degrade α-lactose (156.94 U/mg), maltose (92.59 U/mg), raffinose (86.81 U/mg), and hyaluronic acid (5.71 U/mg). The enzyme activity is optimal at pH 5.0 and 30 ℃, indicating that the hypothetical protein BfLac2275 is a novel and multifunctional CAZymes in the glycoside hydrolases (GHs). These properties indicate that BfLac2275 has broad application prospects in many fields such as plant polysaccharide decomposition, food industry, animal feed additives and enzyme preparations. This study not only serves as a reference for exploring novel CAZymes encoded by gut microbiota but also provides an example for further studying the functional annotation of hypothetical genes in metagenomic assembly genomes.


Asunto(s)
Microbioma Gastrointestinal , Glicósido Hidrolasas , Metagenoma , Animales , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/química , Microbioma Gastrointestinal/genética , Caballos , Genoma Bacteriano , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Especificidad por Sustrato , Filogenia
8.
Anal Chem ; 96(31): 12776-12783, 2024 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-39047235

RESUMEN

The healthcare burden imposed by bacterial infections demands robust and accessible diagnostic methods that can be performed outside hospitals and centralized laboratories. Here, we report Pathogen Assay with Ratiometric Luminescence (PEARL), a sensitive and easy-to-operate platform for detecting pathogenic bacteria. The PEARL leveraged a color-changeable CRISPR-Cas12a sensor and recombinase polymerase amplification to elicit ratiometric bioluminescence responses to target inputs. This platform enabled robust and visualized identification of attomolar bacteria genome deoxyribonucleic acid according to the color changes of the reactions. In addition, the components of the color-changeable Cas12a sensor could be lyophilized for 3 month storage at ambient temperature and then be fully activated with the amplicons derived from crude bacterial lysates, reducing the requirements for cold-chain storage and tedious handling steps. We demonstrated that the PEARL assay is applicable for identifying the infections caused by Pseudomonas aeruginosa in different clinical specimens, including sputa, urines, and swabs derived from wounds. These results revealed the potential of PEARL to be used by untrained personnel, which will facilitate decentralized pathogen diagnosis in community- and resource-limited regions.


Asunto(s)
Sistemas CRISPR-Cas , Mediciones Luminiscentes , Pseudomonas aeruginosa , Sistemas CRISPR-Cas/genética , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/genética , Humanos , Liofilización , Color , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Técnicas Biosensibles , Proteínas Asociadas a CRISPR/metabolismo , Luminiscencia
9.
Sensors (Basel) ; 24(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38894057

RESUMEN

In this article, a novel cross-domain knowledge transfer method is implemented to optimize the tradeoff between energy consumption and information freshness for all pieces of equipment powered by heterogeneous energy sources within smart factory. Three distinct groups of use cases are considered, each utilizing a different energy source: grid power, green energy source, and mixed energy sources. Differing from mainstream algorithms that require consistency among groups, the proposed method enables knowledge transfer even across varying state and/or action spaces. With the advantage of multiple layers of knowledge extraction, a lightweight knowledge transfer is achieved without the need for neural networks. This facilitates broader applications in self-sustainable wireless networks. Simulation results reveal a notable improvement in the 'warm start' policy for each equipment, manifesting as a 51.32% increase in initial reward compared to a random policy approach.

10.
BMC Cancer ; 24(1): 762, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918690

RESUMEN

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.


Asunto(s)
Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Pronóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Adulto , Plaquetas/patología , Anciano , Albúmina Sérica/análisis , Estadificación de Neoplasias , Adulto Joven , Modelos de Riesgos Proporcionales , Recuento de Plaquetas , Biomarcadores de Tumor/sangre
11.
Nanomaterials (Basel) ; 14(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38921866

RESUMEN

Intensive increases in electrical energy storage are being driven by electric vehicles (EVs), smart grids, intermittent renewable energy, and decarbonization of the energy economy. Advanced lithium-sulfur batteries (LSBs) are among the most promising candidates, especially for EVs and grid-scale energy storage applications. In this topical review, the recent progress and perspectives of practical LSBs are reviewed and discussed; the challenges and solutions for these LSBs are analyzed and proposed for future practical and large-scale energy storage applications. Major challenges for the shuttle effect, reaction kinetics, and anodes are specifically addressed, and solutions are provided on the basis of recent progress in electrodes, electrolytes, binders, interlayers, conductivity, electrocatalysis, artificial SEI layers, etc. The characterization strategies (including in situ ones) and practical parameters (e.g., cost-effectiveness, battery management/modeling, environmental adaptability) are assessed for crucial automotive/stationary large-scale energy storage applications (i.e., EVs and grid energy storage). This topical review will give insights into the future development of promising Li-S batteries toward practical applications, including EVs and grid storage.

12.
MedComm (2020) ; 5(6): e585, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38832213

RESUMEN

How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno-occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity-based and pathological distortion-independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single-subject level. Thirty-three machine-learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature-based model for long-term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate "fingerprints" of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

14.
Br J Pharmacol ; 181(17): 3098-3117, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38698737

RESUMEN

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.


Asunto(s)
Angiotensina II , Fibrosis , Hipertensión , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Endogámicos C57BL , Vimentina , Animales , Angiotensina II/toxicidad , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Fibrosis/inducido químicamente , Ratones , Humanos , Vimentina/metabolismo , Masculino , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Ratones Noqueados , Proteínas con Dominio LIM/metabolismo , Proteínas con Dominio LIM/genética
15.
Adv Healthc Mater ; 13(20): e2400003, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38711313

RESUMEN

Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self-healing hydrogel of oxidized konjac glucomannan/arginine-modified chitosan (OKGM/CS-Arg, OC) integrated with protocatechualdehyde-@Fe (PF) nanoparticles capable of effectively absorbing near-infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin-resistant Staphylococcus aureus-infected full-thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti-inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug-resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.


Asunto(s)
Antibacterianos , Antiinflamatorios , Quitosano , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Quitosano/química , Quitosano/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Terapia Fototérmica/métodos , Polisacáridos/química , Polisacáridos/farmacología , Células RAW 264.7 , Mananos/química , Mananos/farmacología , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/terapia
16.
Cell Death Differ ; 31(7): 868-880, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38816579

RESUMEN

Bromodomain containing protein 9 (BRD9), a member of the non-canonical BRG1/BRM-associated factor (ncBAF) chromatin remodeling complex, has been implicated as a synthetic lethal target in AML but its function in normal human hematopoiesis is unknown. In hematopoietic stem and progenitor cells (HSPC) genomic or chemical inhibition of BRD9 led to a proliferative disadvantage and loss of stem cells in vitro. Human HSPCs with reduced BRD9 protein levels produced lower numbers of immature mixed multipotent GEMM colonies in semi-solid media. In lineage-promoting culture conditions, cells with reduced BRD9 levels failed to differentiate into the megakaryocytic lineage and showed delayed differentiation into erythroid cells but enhanced terminal myeloid differentiation. HSPCs with BRD9 knock down (KD) had reduced long-term multilineage engraftment in a xenotransplantation assay. An increased number of downregulated genes in RNAseq analysis after BRD9 KD coupled with a gain in chromatin accessibility at the promoters of several repressive transcription factors (TF) suggest that BRD9 functions in the maintenance of active transcription during HSC differentiation. In particular, the hematopoietic master regulator GATA1 was identified as one of the core TFs regulating the gene networks modulated by BRD9 loss in HSPCs. BRD9 inhibition reduced a GATA1-luciferase reporter signal, further suggesting a role for BRD9 in regulating GATA1 activity. BRD9 is therefore an additional example of epigenetic regulation of human hematopoiesis.


Asunto(s)
Diferenciación Celular , Linaje de la Célula , Células Madre Hematopoyéticas , Factores de Transcripción , Humanos , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/citología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Animales , Factor de Transcripción GATA1/metabolismo , Factor de Transcripción GATA1/genética , Ratones , Hematopoyesis , Proteínas que Contienen Bromodominio
17.
Cereb Cortex ; 34(13): 104-111, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696603

RESUMEN

Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.


Asunto(s)
Trastorno Autístico , Comunicación , Espectroscopía Infrarroja Corta , Humanos , Masculino , Femenino , Adulto Joven , Trastorno Autístico/psicología , Trastorno Autístico/fisiopatología , Relaciones Interpersonales , Conducta Social , Interacción Social , Encéfalo/fisiopatología , Encéfalo/fisiología , Adulto , Sincronización Cortical/fisiología , Adolescente
18.
Adv Healthc Mater ; : e2400671, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695384

RESUMEN

Skin anti-aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water-responsive self-contraction capabilities, leading to the development of innovative self-contracting silk-based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self-contraction, near-infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self-contraction properties, drug-loading and sustained-release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near-infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti-aging.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38700966

RESUMEN

This article puts forth a new training data-untethered model poisoning (MP) attack on federated learning (FL). The new MP attack extends an adversarial variational graph autoencoder (VGAE) to create malicious local models based solely on the benign local models overheard without any access to the training data of FL. Such an advancement leads to the VGAE-MP attack that is not only efficacious but also remains elusive to detection. VGAE-MP attack extracts graph structural correlations among the benign local models and the training data features, adversarially regenerates the graph structure, and generates malicious local models using the adversarial graph structure and benign models' features. Moreover, a new attacking algorithm is presented to train the malicious local models using VGAE and sub-gradient descent, while enabling an optimal selection of the benign local models for training the VGAE. Experiments demonstrate a gradual drop in FL accuracy under the proposed VGAE-MP attack and the ineffectiveness of existing defense mechanisms in detecting the attack, posing a severe threat to FL.

20.
Amino Acids ; 56(1): 31, 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38616233

RESUMEN

Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.


Asunto(s)
Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Animales , Ratones , Hemorragia Subaracnoidea/tratamiento farmacológico , Taurina/farmacología , Astrocitos , Apoptosis , Aminoácidos
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