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1.
Artículo en Inglés | MEDLINE | ID: mdl-38934914

RESUMEN

Attentional bias modification (ABM) has been proposed to treat tobacco use disorder by reducing attentional bias (AB) to smoking-related cues. We sought to determine the extent to which AB to smoking cues, as measured by eye-tracking technology, was sensitive to multisession ABM among treatment-seeking adult smokers. The participants (N = 203; 74 women) completed 13 days of daily ABM or sham training using a smartphone, followed by 8 weeks of nicotine replacement therapy and cessation counseling. ABM and sham training were administered using the modified dot-probe task (i.e., neutral cues probed 100% of the time) and the unmodified dot-probe task (i.e., cue types probed equally), respectively. Eye gaze dwell time proportions to paired presentations of smoking and neutral cues were measured at baseline, 1 day post-ABM training, and 8 weeks post-ABM training. At baseline, younger, more dependent smokers and those with higher smoking satisfaction scores looked longer at smoking cues than neutral ones. ABM training resulted in greater gaze preference for the smoking cues than sham training at 1 day posttraining. Gaze preference for smoking cues was positively associated with AB to smoking cues as measured by reaction time during the laboratory dot-probe assessment. At 8 weeks posttraining, gaze preference was not associated with any of the smoking outcome measures. These findings suggest that multisession ABM training resulted in changes in AB by increasing time spent looking at neutral compared with smoking cues in the short term. However, this effect was not sustained and was not associated with smoking behavior outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Elife ; 122024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829202

RESUMEN

Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown in zebrafish or genetic knockout in mice, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one with Styxl2 being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role in de novo sarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions in de novo sarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotes de novo sarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.


Asunto(s)
Ratones Noqueados , Sarcómeros , Pez Cebra , Animales , Ratones , Proteolisis , Sarcómeros/metabolismo , Pez Cebra/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo
3.
Angew Chem Int Ed Engl ; : e202403473, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829678

RESUMEN

Covalent polymerization of organic molecules into crystalline one-dimensional (1D) polymers is effective for achieving desired thermal, optical, and electrical properties, yet it remains a persistent synthetic challenge for their inherent tendency to adopt amorphous or semicrystalline phases. Here we report a strategy to synthesize crystaline 1D covalent organic frameworks (COFs) composing quasi-conjugated chains with benzoxazine linkages via the one-pot Mannich reaction. Through [4+2] and [2+2] type Mannich condensation reactions, we fabricated stoichiometric and sub-stoichiometric 1D covalent polymeric chains, respectively, using doubly and singly-linked benzoxazine ring. The validity of their crystal structures has been directly visualized through the state-of-the-art cryogenic low-dose electron microscopy techniques. Post-synthetic functionalizations of them with a chiral MacMillan catalyst produce crystaline organic photocatalysts that demonstrated excellent catalytic and recyclable performance in light-driven asymmetric alkylation of aldehydes, affording up to 94% enantiomeric excess.

4.
Zhongguo Fei Ai Za Zhi ; 27(5): 383-390, 2024 May 20.
Artículo en Chino | MEDLINE | ID: mdl-38880926

RESUMEN

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches.
.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/uso terapéutico
6.
Hum Vaccin Immunother ; 20(1): 2358570, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38853516

RESUMEN

Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc - a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively - and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.


Asunto(s)
Anticuerpos Neutralizantes , Toxinas Botulínicas Tipo A , Botulismo , ARN Mensajero , Anticuerpos Neutralizantes/inmunología , Animales , Botulismo/prevención & control , Botulismo/inmunología , Toxinas Botulínicas Tipo A/inmunología , ARN Mensajero/genética , ARN Mensajero/inmunología , Ratones , Humanos , Femenino , Nanopartículas , Ratones Endogámicos BALB C , Anticuerpos Antibacterianos/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Liposomas
7.
J Craniofac Surg ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861329

RESUMEN

Reconstructive surgery plays a crucial role in addressing congenital defects, posttraumatic deformities, and related conditions, providing transformative solutions for patients. Its primary goal is to restore or enhance damaged tissue structures, improving both functionality and appearance, and empowering individuals to lead fulfilling lives. Take, for example, a female patient who experienced a nasal infection after a cat bite. Despite initial treatment, she developed severe scar contractures and excessive scar tissue within her nostrils, significantly impacting her quality of life. Seeking assistance, she consulted the authors' plastic and reconstructive surgery team. By utilizing various flap techniques, the authors embarked on the intricate journey of reconstructing her nasal framework, ultimately restoring both form and function.

8.
Indian J Dermatol ; 69(2): 178-180, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841217

RESUMEN

In recent years, with the increased usage of tumour necrosis factor (TNF) inhibitors, more side effects have been revealed. Paradoxical psoriasis, including psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations, is a common adverse effect. However, erythrodermic psoriasis associated with alopecia due to anti-TNF-α is rarely reported in the literature. We report a 44-year-old woman who developed erythrodermic psoriasis associated with diffuse alopecia during her treatment with adalimumab for palmoplantar pustulosis.

9.
Poult Sci ; 103(8): 103893, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38870615

RESUMEN

Most of follicles undergo a degenerative process called follicular atresia. This process directly affects the egg production of laying hens and is regulated by external and internal factors. External factors primarily include nutrition and environmental factors. In follicular atresia, internal factors are predominantly regulated at 3 levels; organic, cellular and molecular levels. At the organic level, the hypothalamic-pituitary-ovary (HPO) axis plays an essential role in controlling follicular development. At the cellular level, gonadotropins and cytokines, as well as estrogens, bind to their receptors and activate different signaling pathways, thereby suppressing follicular atresia. By contrast, oxidative stress induces follicular atresia by increasing ROS levels. At the molecular level, granulosa cell (GC) apoptosis is not the only factor triggering follicular atresia. Autophagy is also known to give rise to atresia. Epigenetics also plays a pivotal role in regulating gene expression in processes that seem to be related to follicular atresia, such as apoptosis, autophagy, proliferation, and steroidogenesis. Among these processes, the miRNA regulation mechanism is well-studied. The current review focuses on factors that regulate follicular atresia at organic, cellular and molecular levels and evaluates the interaction network among these levels. Additionally, this review summarizes atretic follicle characteristics, in vitro modeling methods, and factors preventing follicular atresia in laying hens.

10.
Front Immunol ; 15: 1339680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881906

RESUMEN

Background: SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear. Methods: We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes. Results: Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response. Conclusion: Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.


Asunto(s)
Proliferación Celular , Ácido Fólico , Lupus Eritematoso Sistémico , Monocitos , Receptor Toll-Like 4 , Transcobalaminas , Humanos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/inmunología , Monocitos/metabolismo , Monocitos/inmunología , Transcobalaminas/metabolismo , Transcobalaminas/genética , Femenino , Ácido Fólico/metabolismo , Masculino , Adulto , Inflamación/metabolismo , Inflamación/inmunología , Persona de Mediana Edad , Células THP-1 , Carbono/metabolismo , Vitamina B 12/metabolismo , Estudios de Casos y Controles
11.
JAMA ; 331(20): 1722-1731, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38696203

RESUMEN

Importance: Most people who smoke do not quit on their initial attempt. Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT). Design, Setting, and Participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic. Interventions: The initial treatment was 2 mg/d of varenicline or the combined replacement therapy of a 21-mg patch plus 2-mg lozenge. The rerandomized participants either continued with their initial therapies, switched between varenicline and CNRT, or increased dosages either to 3-mg or more of varenicline or to a 42-mg patch and lozenges. All received weekly brief counseling. Main Outcomes and Measures: Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks. Results: The 490 randomized participants (210 female [43%], 287 non-Hispanic White [58%], mean age, 48.1 years) smoked an average of 20 cigarettes per day. After the first phase, 54 participants in the CNRT group were abstinent and continued their therapy; of the 191 who were not abstinent, 151 were rerandomized, and the 40 who did not return for rerandomization were assigned to continue their initial CNRT condition in phase 2. The end-of-treatment abstinence rate for the 191 phase 1 nonabstainers was 8% (95% credible interval [CrI], 6% to 10%) for the 90 (47%) who continued at the dosage condition, 14% (CrI, 10% to 18%) for the 50 (33%) who increased their dosage, and 14% (95% CrI, 10% to 18%) for the 51 (34%) who switched to varenicline (absolute risk difference [RD], 6%; 95% CrI, 6% to 11%) with more than 99% posterior probability that either strategy conferred benefit over continuing the initial dosage. After the first phase, 88 participants in the varenicline group were abstinent and continued their therapy; of the 157 who were not abstinent, 122 were rerandomized and 35 who did not return for rerandomization were assigned to continue with the varenicline condition. The end-of-treatment abstinence rate for the 157 phase 1 nonabstainers was 20% (95% CrI, 16% to 26%) for the 39 (32%) who increased their varenicline dosage, 0 (95% CrI, 0 to 0) for the 41 (34%) who switched CNRT, and 3% (95% CrI, 1% to 4%) for the 77 (49%) who were assigned to the continued varenicline condition (absolute RD, -3%; 95% CrI, -4% to -1%) with more than 99% posterior probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage. Furthermore, increasing the varenicline dosage had an absolute RD of 18% (95% CrI, 13% to 24%) and a more than 99% posterior probability of conferring benefit. The secondary outcome of continuous abstinence at 6 months indicated that only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages. Conclusions and Relevance: For individuals who smoked but did not achieve abstinence after treatment with varenicline, increasing the dosage enhanced abstinence vs continuing, whereas for nonabstainers initially treated with CNRT, a dosage increase or switch to varenicline enhanced abstinence and may be viable rescue strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT02271919.


Asunto(s)
Nicotina , Agonistas Nicotínicos , Agentes para el Cese del Hábito de Fumar , Cese del Hábito de Fumar , Vareniclina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Doble Ciego , Nicotina/administración & dosificación , Nicotina/efectos adversos , Nicotina/uso terapéutico , Agonistas Nicotínicos/administración & dosificación , Agonistas Nicotínicos/uso terapéutico , Cese del Hábito de Fumar/métodos , Agentes para el Cese del Hábito de Fumar/uso terapéutico , Agentes para el Cese del Hábito de Fumar/efectos adversos , Agentes para el Cese del Hábito de Fumar/administración & dosificación , Insuficiencia del Tratamiento , Vareniclina/uso terapéutico , Vareniclina/administración & dosificación , Vareniclina/efectos adversos , Blanco
12.
Artículo en Inglés | MEDLINE | ID: mdl-38754749

RESUMEN

OBJECTIVE: The mechanism of left ventricular outflow tract obstruction (LVOTO) is complex in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the impact of mitral valve geometry on LVOTO by echocardiography. MATERIALS AND METHODS: The study population comprised 177 consecutive patients with HCM. Morphological findings of left ventricular hypertrophy and LVOTO-related abnormalities were assessed by comprehensive transthoracic echocardiography. Aortomitral angle, mitral leaflet length, and coaptation height were measured and analyzed at rest. Multivariable stepwise forward logistic regression analysis was performed to identify geometric predictors of LVOTO. RESULTS: One hundred thirty-seven patients had an LVOT gradient ≥30 mm Hg. Multivariable logistic regression showed that aortomitral angle (odds ratio [OR], 0.89; 95% CI, 0.83-0.95, P < .001), coaptation height (OR, 1.96; 95% CI, 1.41-2.72, P < .001), and accessory mitral valve chordae tendineae (OR, 13.1; 95% CI, 4.32-39.95; P < .001) were independently associated with LVOTO. Receiver operating characteristic analysis showed that the area under the curve of mitral coaptation height was higher (area under the curve = 0.815) than the other 2 indicators (P < .05). CONCLUSION: Mitral coaptation height, aortomitral angle, and accessory mitral valve chordae tendineae were important predictors of SAM and LVOTO in HCM independent of septal hypertrophy.

13.
BMC Musculoskelet Disord ; 25(1): 359, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711079

RESUMEN

BACKGROUND: With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited. OBJECTIVE: We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs. METHODS: We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed. RESULTS: miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH. CONCLUSION: miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.


Asunto(s)
Adenosina/análogos & derivados , Diferenciación Celular , Células Madre Mesenquimatosas , MicroARNs , Osteogénesis , Proteínas de Unión al ARN , MicroARNs/genética , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Osteogénesis/genética , Humanos , Necrosis de la Cabeza Femoral/genética , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/inducido químicamente , Células Cultivadas , Apoptosis , Adenosina/metabolismo , Animales , Masculino , Metilación , Proliferación Celular , Lipogénesis/genética
14.
Angew Chem Int Ed Engl ; : e202406956, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713527

RESUMEN

Supramolecular assembly frameworks (SAFs) represent a new category of porous materials, utilizing non-covalent interactions, setting them apart from metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). This category includes but is not restricted to hydrogen-bonded organic frameworks and supramolecular organic frameworks. SAFs stand out for their outstanding porosity, crystallinity, and stability, alongside unique dissolution-recrystallization dynamics that enable significant structural and functional modifications. Crucially, their non-covalent assembly strategies allow for a balanced manipulation of porosity, symmetry, crystallinity, and dimensions, facilitating the creation of advanced crystalline porous materials unattainable through conventional covalent or coordination bond synthesis. Despite their considerable promise in overcoming several limitations inherent to MOFs and COFs, particularly in terms of solution-processability, SAFs have received relatively little attention in recent literature. This Minireview aims to shed light on standout SAFs, exploring their design principles, synthesis strategies, and characterization methods. It emphasizes their distinctive features and the broad spectrum of potential applications across various domains, aiming to catalyze further development and practical application within the scientific community.

15.
Front Immunol ; 15: 1369972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690285

RESUMEN

Background: Temozolomide (TMZ) is a key component in the treatment of gliomas. Hypermutation induced by TMZ can be encountered in routine clinical practice, and its significance is progressively gaining recognition. However, the relationship between TMZ-induced hypermutation and the immunologic response remains controversial. Case presentation: We present the case of a 38-year-old male patient who underwent five surgeries for glioma. Initially diagnosed with IDH-mutant astrocytoma (WHO grade 2) during the first two surgeries, the disease progressed to grade 4 in subsequent interventions. Prior to the fourth surgery, the patient received 3 cycles of standard TMZ chemotherapy and 9 cycles of dose-dense TMZ regimens. Genomic and immunologic analyses of the tumor tissue obtained during the fourth surgery revealed a relatively favorable immune microenvironment, as indicated by an immunophenoscore of 5, suggesting potential benefits from immunotherapy. Consequently, the patient underwent low-dose irradiation combined with immunoadjuvant treatment. After completing 4 cycles of immunotherapy, the tumor significantly shrank, resulting in a partial response. However, after a 6-month duration of response, the patient experienced disease progression. Subsequent analysis of the tumor tissue obtained during the fifth surgery revealed the occurrence of hypermutation, with mutation signature analysis attributing TMZ treatment as the primary cause. Unfortunately, the patient succumbed shortly thereafter, with a survival period of 126 months. Conclusion: Patients subjected to a prolonged regimen of TMZ treatment may exhibit heightened vulnerability to hypermutation. This hypermutation induced by TMZ holds the potential to function as an indicator associated with unfavorable response to immunotherapy in gliomas.


Asunto(s)
Antineoplásicos Alquilantes , Neoplasias Encefálicas , Glioma , Mutación , Temozolomida , Humanos , Temozolomida/uso terapéutico , Masculino , Adulto , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Glioma/genética , Glioma/terapia , Glioma/tratamiento farmacológico , Antineoplásicos Alquilantes/uso terapéutico , Inmunoterapia/métodos , Resultado Fatal , Microambiente Tumoral/inmunología
16.
Int J Biol Macromol ; 268(Pt 1): 131833, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38663703

RESUMEN

The emergence and widespread of multidrug-resistant Gram-negative bacteria have posed a severe threat to human health and environmental safety, escalating into a global medical crisis. Utilization of antibiotic adjuvants is a rapid approach to combat bacterial resistance effectively since the development of new antimicrobial agents is a formidable challenge. NhaA, driven by proton motive force, is a crucial secondary transporter on the cytoplasmic membrane of Escherichia coli. We found that 2-Aminoperimidine (2-AP), which is a specific inhibitor of NhaA, could enhance the activity of colistin against sensitive E. coli and reverse the resistance in mcr-1 positive E. coli. Mechanistic studies indicated that 2-AP induced dysfunction in cytoplasmic membrane through the suppression of NhaA, leading to metabolic inhibition and ultimately enhancing the sensitivity of E. coli to colistin. Moreover, 2-AP restored the efficacy of colistin against resistant E. coli in two animal infection models. Our findings reveal the potential of NhaA as a novel target for colistin adjuvants, providing new possibilities for the clinical application of colistin.


Asunto(s)
Colistina , Proteínas de Escherichia coli , Escherichia coli , Colistina/farmacología , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/metabolismo , Animales , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/efectos de los fármacos , Ratones , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología
17.
BMC Genomics ; 25(1): 374, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627644

RESUMEN

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.


Asunto(s)
Anomalías Múltiples , Anomalías Craneofaciales , Dieta con Restricción de Proteínas , Hígado Graso , Trastornos del Crecimiento , Defectos del Tabique Interventricular , Animales , Femenino , Histonas/metabolismo , Pollos/genética , Pollos/metabolismo , Epigénesis Genética , Hígado Graso/genética , Hígado Graso/veterinaria , Hemorragia/genética , Transcriptoma
18.
Front Oncol ; 14: 1376502, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628672

RESUMEN

Purpose: Dysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study. Patients and methods: A total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database. Results: miR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121). Conclusion: Upregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

19.
Adv Mater ; : e2402575, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38631046

RESUMEN

Organic photovoltaic (OPV) technology holds tremendous promise as a sustainable power source for underwater off-grid systems. However, research on underwater OPV cells is relatively scarce. Here, this gap is addressed by focusing on the exploration and development of OPV cells specifically designed for underwater applications. An acceptor, named ITO-4Cl, with excellent water resistance, is rationally designed and synthesized. Benefiting from its low energetic disorder and an absorption spectrum well-suited to the underwater environment, the ITO-4Cl-based OPV cell achieves an unprecedented power conversion efficiency (PCE) of over 25.6% at a water depth of 1 m. Additionally, under 660 nm laser irradiation, the cell demonstrates a notable PCE of 31.6%, indicating its potential for underwater wireless energy transfer. Due to the mitigation of thermal effects from solar irradiation, the lifetime of the ITO-4Cl-based OPV cell exceeds 7000 h. Additionally, a flexible OPV cell is fabricated that maintains its initial PCE even under exposure to high pressures of 5 MPa. A 32.5 cm2 flexible module achieves an excellent PCE of 17%. This work fosters a deeper understanding of underwater OPV cells and highlights the promising prospects of OPV cells for underwater applications.

20.
Medicine (Baltimore) ; 103(17): e37985, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669368

RESUMEN

RATIONALE: Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging. PATIENT CONCERNS: A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment. DIAGNOSIS: After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma. INTERVENTIONS: After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful. OUTCOMES: On the tenth day after surgery, the patient vital signs were stable, and he was discharged. LESSONS: Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival.


Asunto(s)
Mesotelioma Maligno , Neoplasias Retroperitoneales , Humanos , Adulto , Femenino , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/terapia , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/patología , Mesotelioma Maligno/terapia , Mesotelioma/diagnóstico , Mesotelioma/patología , Mesotelioma/terapia , Mesotelioma/cirugía , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Laparoscopía/métodos
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