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1.
Methods Mol Biol ; 2854: 1-7, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39192112

RESUMEN

Antiviral innate immunity is a complicated system initiated by the induction of type I interferon (IFN-I) and downstream interferon-stimulated genes (ISGs) and is finely regulated by numerous positive and negative factors at different signaling adaptors. During this process, posttranslational modifications, especially ubiquitination, are the most common regulatory strategy used by the host to switch the antiviral innate signaling pathway and are mainly controlled by E3 ubiquitin ligases from different protein families. A comprehensive understanding of the regulatory mechanisms and a novel discovery of regulatory factors involved in the IFN-I signaling pathway are important for researchers to identify novel therapeutic targets against viral infectious diseases based on innate immunotherapy. In this section, we use the E3 ubiquitin ligase as an example to guide the identification of a protein belonging to the RING Finger (RNF) family that regulates the RIG-I-mediated IFN-I pathway through ubiquitination.


Asunto(s)
Inmunidad Innata , Interferón Tipo I , Transducción de Señal , Ubiquitina-Proteína Ligasas , Ubiquitinación , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Interferón Tipo I/metabolismo , Virosis/inmunología , Virosis/genética , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genética , Proteína 58 DEAD Box/metabolismo , Proteína 58 DEAD Box/genética
2.
Neural Regen Res ; 20(1): 277-290, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767492

RESUMEN

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

3.
J Cancer ; 15(16): 5244-5257, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247590

RESUMEN

ENG/CD105 encodes a vascular endothelial glycoprotein and plays a crucial role in modulating angiogenesis. However, the significance of ENG expression, DNA methylation, immuno-response, and cordycepin (CD) regulation as diagnostic, prognostic, and therapeutic markers for breast invasive carcinoma (BRCA) remains unclear. As a result, ENG is decreased in BRCA tissues compared with corresponding healthy tissues. Five isoforms were found, and the utilization for ENG isoform (ENG-002) was the highest, suggesting its potential involvement in important roles in BRCA. ENG DNA was frequently altered in most types of cancer, and overall survival (OS) for mutant ENG was significantly longer than for wild-type cases. High expressions of ENG remarkably correlate with long relapse-free survival (RFS) for breast cancer (BC). Additionally, the ENG methylation level was higher in BRCA tissues compared with matched healthy tissues. The ENG expression and DNA methylation showed a significantly reverse correlation, demonstrating that ENG methylation may be a regulatory mechanism. By constructing diagnostic and prognostic models of ENG methylation for BRCA, we found four CpGs (CpG sites) that ranked with high importance. High methylation for cg14185922 of ENG in BRCA tissues showed shorter OS (high risk), indicating that ENG CpGs' methylation has potential as a diagnostic and prognostic biomarker for BRCA. Moreover, ENG might be a novel target for tumor immune response and immunotherapy in pancancer, including BC. CD, an adenosine analog and anti-cancer agent, increased ENG levels in a dose-dependent manner in animal models. This suggests that CD repressed BC growth and metastasis, at least partially through increasing the expression of the tumor suppressor gene ENG. Thus, our study successfully evaluated ENG/CD105 expression, DNA methylation, immune response, and CD regulation, which act as a novel diagnostic, prognostic, and therapeutic biomarker for BRCA. This research also fills critical knowledge gaps in this ENG/cancer field and highlights ENG's potential importance for the diagnosis, prognosis, and treatment of BRCA.

4.
J Med Internet Res ; 26: e49362, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250213

RESUMEN

BACKGROUND: Male factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China. OBJECTIVE: The primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China. METHODS: A nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users' behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2. RESULTS: At T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96). CONCLUSIONS: The enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611.


Asunto(s)
Infecciones por VIH , Heterosexualidad , Humanos , Masculino , Adulto , Infecciones por VIH/prevención & control , Heterosexualidad/estadística & datos numéricos , China , Femenino , Trabajadores Sexuales/estadística & datos numéricos , Conducta Sexual , Parejas Sexuales , Adulto Joven
5.
Am J Ophthalmol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39237050

RESUMEN

PURPOSE: This study aimed to investigate longitudinal changes in choroidal thickness (CT) and ganglion cell-inner plexiform layer thickness (GC-IPLT) across distinct phenotypes of type 2 diabetes mellitus (T2DM) patients. DESIGN: Prospective observational cohort study. METHODS: T2DM patients were categorized into five groups (SAID, SIDD, SIRD, MOD, and MARD) using K-means clustering based on ß-cell function and insulin resistance. Swept-source optical coherence tomography measured baseline and 4-year follow-up CT and GC-IPLT. Linear mixed-effects models assessed absolute and relative changes in CT and GC-IPLT across subtypes. RESULTS: Over a median 4.11-year follow-up, CT and GC-IPLT decreased significantly across all groups. Choroidal thinning rates were most pronounced in SIDD (-6.5±0.53 µm/year and -3.5±0.24%/year) and SAID (-6.27±0.8 µm/year and -3.19±0.37%/year), while MARD showed the slowest thinning (-3.63±0.34 µm/year and -1.98±0.25%/year). SIRD exhibited the greatest GC-IPLT loss (-0.66±0.05 µm/year and -0.91±0.07%/year), with the least in SIDD (-0.36±0.05 µm/year and -0.49±0.07%/year), all statistically significant (Ps < 0.001). Adjusted for variables, SIDD and SAID groups showed faster CT thinning than MARD [-2.57 µm/year (95% CI: -4.16 to -0.97; P=0.002) and -2.89 µm/year (95% CI: -4.12 to -1.66; P<0.001), respectively]. GC-IPLT thinning was notably accelerated in SIRD versus MARD, but slowed in SIDD relative to MARD [differences of -0.16 µm/year (95% CI: -0.3 to -0.03; P=0.015) and 0.15 µm/year (95% CI: 0.03 to 0.27; P=0.015), respectively]. Stratified analysis revealed significant differences among non-DR groups. CONCLUSIONS: Microvascular damage in the choroid is associated with SIDD patients, whereas early signs of retinal neurodegeneration are evident in SIRD patients. All these changes may precede the onset of DR.

6.
Chem Commun (Camb) ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39239693

RESUMEN

We propose a simple strategy to fabricate a composite material consisting of amino-functionalized carbon nanotubes (NCNTs) grafted with a covalently bonded Ni(II)-based covalent organic framework (COF) for electrocatalytic water splitting. The resulting electrocatalyst demonstrates remarkable catalytic efficiency in both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) under alkaline conditions.

7.
Acta Parasitol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225736

RESUMEN

BACKGROUND: Colonic schistosomiasis is a significant health issue in endemic areas, presenting diagnostic challenges due to its nonspecific clinical symptoms and radiographic features. This case report highlights a patient with concomitant colorectal cancer and chronic Schistosoma japonicum infection, emphasizing the need for a comprehensive diagnostic approach. CASE PRESENTATION: A 67-year-old male from an endemic region presented with a six-month history of intermittent hematochezia. Initial colonoscopy revealed multiple mucosal elevations in the sigmoid colon and rectum. Subsequent investigations, including CT scans and endoscopic ultrasonography, indicated high echogenic changes and multiple lesions. The patient underwent endoscopic submucosal dissection (ESD), revealing adenocarcinoma of the rectal mucosa and tubular adenoma in the sigmoid colon, both with extensive deposition of Schistosoma japonicum eggs. Postoperative pathology confirmed the diagnosis of moderately differentiated adenocarcinoma with chronic schistosomiasis. CONCLUSION: This case underscores the diagnostic complexity of colonic schistosomiasis, particularly when coexisting with malignancy. The integration of colonoscopy, histopathology, and auxiliary tests is crucial for accurate diagnosis. Clinicians should maintain a high index of suspicion for schistosomiasis in patients from endemic areas presenting with gastrointestinal symptoms. Regular screening and detailed medical histories are essential for early detection and treatment, improving patient outcomes and reducing the risk of misdiagnosis.

8.
Am J Transl Res ; 16(8): 3922-3937, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262709

RESUMEN

OBJECTIVE: To elucidate the underlying mechanism of iron deficiency augmented Angiotensin II-induced aortic medial degeneration. METHODS: ApoE-/- mice were randomly divided into four groups: normal control group (NC group), Angiotensin II (Ang II) subcutaneous pumped alone Group (Ang II group), iron deficiency (ID) group (ID group) and ID+Ang II group. The survival time, systolic blood pressure (SBP), and aortic medial degeneration (AMD) formation were monitored. Iron deposition in the aortas was assessed using Prussian blue iron staining. The expression of iron metabolism indicators, aortopathies and the cytoskeleton of vascular smooth muscle cells (VSMCs) were analyzed. In an in vitro setting, deferoxamine (DFO) was employed to mimic ID to examine the effects of Ang II on the cytoskeletal and contractile function of VSMCs during ID. Ras-related C3 botulinum toxin substrate 1 (Rac-1) expression was inhibited with EHT1864 to verify the role of Cdc42/Rac1 pathway in this pathological process. Blood samples were collected from 150 patients with aortic dissection (AD) and 60 patients with hypertension who were admitted to the Department of Cardiovascular Surgery at Renmin Hospital of Wuhan University between June 2018 and September 2019. The aortic tissues were obtained during the surgical treatment of Stanford type A AD patients and the heart donor. The iron metabolism status in plasma and aortic tissue was analyzed. RESULTS: In vivo experiments revealed that, in comparison to the NC and ID groups, mice in the Ang II and ID+Ang II groups exhibited increased SBP, significantly reduced survival time, and an expanded range of aortic dissection (P < 0.05). ID feeding augmented the Ang II-induced aortopathies. Both in vitro and in vivo results indicated that ID led to diminished expression of phosphorylated myosin light chain (p-MLC) and recombinant Cell Division Cycle Protein 42 (Cdc42) in VSMCs, while Rac-1 expression increased. The clinical sample testing data further confirmed the discovery that individuals diagnosed with AD display ID in both the plasma and the diseased aortas. CONCLUSIONS: The Cdc42/Rac1 pathway plays a crucial role in disrupting the cytoskeleton of vascular smooth muscle cells during iron deficiency, which leads to aortic medial degeneration both in vivo and in vitro.

9.
Minerva Anestesiol ; 90(9): 785-796, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39279483

RESUMEN

Postoperative delirium (POD) is a prevalent perioperative complication among elderly individuals and is a cause of significant detrimental consequences for both individuals and society. Pharmacological and nonpharmacological prevention methods/therapies have been proposed to mitigate the risk of POD. Nevertheless, the efficacy of pharmacological interventions is controversial, and some of them cause side effects. Therefore, numerous studies have explored the effectiveness of nonpharmacological interventions in mitigating POD and have recommended the use of nonpharmacological multicomponent interventions by an interdisciplinary team as primary interventions. However, dedicated units aimed at promoting comanagement are rare and are only present in academic hospitals. Therefore, there is increasing interest in nonpharmacological mono-component interventions for preventing POD, which offer advantages such as easy application, cost-effectiveness, patient acceptability and noninvasiveness. These interventions are divided into cognitive training and noncognitive interventions. The former is aimed at increasing cognitive reserve, thus decreasing the incidence rate of POD. Noncognitive interventions, including sensory stimuli (music therapy, odor enrichment), improving sleep disturbances, physical activity, acupuncture and transcranial magnetic/direct current stimulation, are aimed at decreasing the risk factors for POD. This review provides a comprehensive overview of recently reported nonpharmacological mono-component interventions for preventing POD and briefly describes their clinical value.


Asunto(s)
Delirio , Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/terapia , Delirio/prevención & control , Delirio/etiología , Delirio/terapia
10.
World J Clin Cases ; 12(26): 5946-5951, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39286381

RESUMEN

BACKGROUND: Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages. CASE SUMMARY: We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura, which was not taken seriously enough. As the disease progressed, pleural effusion gradually appeared, and after systematic diagnosis and treatment, she was diagnosed with "primary light chain amyloidosis". She achieved rapid hematological remission after treatment with a daratumumab + bortezomib + cyclophosphamide + dexamethasone regimen. CONCLUSION: Periorbital purpura can be the only initial symptom of primary light chain amyloidosis; we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.

11.
Quant Imaging Med Surg ; 14(9): 6413-6424, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39281170

RESUMEN

Background: Viral pneumonia (VP) often leads to the development of deep vein thrombosis (DVT) in hospitalized patients. The aim of the study was to investigate the incidence of DVT in discharged patients with VP, and whether new and old DVT differ in transverse relaxation time. Methods: In this prospective cohort study in Wuhan, China, 338 consecutive discharged VP patients from February 2021 to March 2023 who underwent T2 weighted Sampling Perfection with Application Optimized Contrast Evolution (SPACE) were recruited to detect DVT. T2 mapping and T2* mapping were performed for the patients with DVT detected by magnetic resonance imaging (MRI). The minimum, maximum, mean of T2 time and T2* time of DVT were recorded as T2min, T2max, T2mean, T2*min, T2*max, and T2*mean, respectively. Clinical data and laboratory findings were compared between new and old DVT cases, which were defined based on the examination results before and after discharge. A Mann-Whitney test was used to compare transverse relaxation time parameters between new and old DVT. Results: Twelve percent of VP patients (40/338) developed new DVT after discharge. Thirty-three out of 104 DVTs did not resolve after discharge. Compared with patients with new DVT, patients with old DVT were older (67 vs. 59 years, P=0.003); and had a higher proportion of bedridden time >72 hours (72.7% vs. 37.0%, P<0.001). Patients with old DVT had a lower lymphocyte count (0.67×109/L vs. 0.97×109/L, P=0.01), higher C-reactive protein (59 vs. 35 mg/L, P=0.019), and higher levels of D-dimer (6.7 vs. 0.9 µg/mL, P<0.001) than patients with new DVT. Patients with old DVT received more invasive mechanical ventilation (30.3% vs. 7.4%, P<0.001) and had a higher proportion of acute respiratory distress syndrome (75.8% vs. 51.9%, P<0.001), and a higher proportion of cardiac injury (39.4% vs. 14.8%, P=0.033) than patients with new DVT. T2min, T2max, T2mean, and T2*max of new DVT were significantly greater than old DVT (17.6±10.4 vs. 13.2±5.9 ms, 94.9±44.9 vs. 42.3±23.6 ms, 46.8±24.0 vs. 25.0±12.6 ms, 22.5±12.4 vs. 10.7±3.5 ms, P<0.05 for all). There was no significant difference in T2*min or T2*mean between new and old DVT (3.2±0.4 vs. 3.1±0.4 ms, 8.2±4.9 vs. 5.5±1.5 ms, P>0.05 for both). Conclusions: T2 weighted SPACE magnetic resonance (MR) is valuable in the follow-up of thrombosis of discharged VP patients. T2 mapping distinguishes between new and old DVT.

12.
Aging Med (Milton) ; 7(4): 528-534, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39234199

RESUMEN

Dementia is characterized by a progressive decline in cognition, behavioral and psychological symptoms (BPSD), and quality of life (QoL). The lack of curative therapies has led to a psychosocial discourse prioritizing QoL of people thriving with dementia (PTD). Group reminiscence therapy (RT) is a relatively inexpensive intervention, with music prompts being a preferred choice, owing to robust musical memory in the early disease stage. However, a synthesis of current evidence is needed to inform research and clinical use of group music RT in dementia care. Therefore, we conducted a systematic review on PubMed, Scopus, CINAHL, APA PsycInfo, and APA PsycArticles to critically appraise published randomized controlled trials examining group music RT to improve cognition, BPSD, and QoL in PTD. Of 14,725 articles, two RCTs involving 102 PTD were included. All studies used prerecorded music for group music RT. All studies were deemed of good quality, adhering to intention-to-treat analysis and assessor blinding. Based on the American Academy of Neurology guidelines, we assigned a Level C recommendation for group music RT for cognition and Level B recommendations for BPSD and QoL (ineffective). In conclusion, group music RT may be useful for symptomatic management in PTD. However, heterogeneous study designs, disease severity, dementia subtype, and outcome measures are likely barriers to meaningful clinical translation. Therefore, the rating of recommendations only serves as a point of reference. Future avenues include live performances as prompts for group music RT.

13.
Front Immunol ; 15: 1442673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234249

RESUMEN

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Células Asesinas Naturales , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Células Asesinas Naturales/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Inmunoterapia/métodos , Animales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/inmunología , Escape del Tumor/efectos de los fármacos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Transducción de Señal , Cetuximab/uso terapéutico , Cetuximab/farmacología
14.
Nat Commun ; 15(1): 7608, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218986

RESUMEN

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.


Asunto(s)
Oryza , Enfermedades de las Plantas , Proteínas de Plantas , Activación Transcripcional , Ubiquitina-Proteína Ligasas , Ubiquitinación , Enfermedades de las Plantas/microbiología , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fosforilación , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Inmunidad de la Planta/genética , Ascomicetos
15.
Phytochemistry ; 229: 114287, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276823

RESUMEN

Chemical investigation of the acid hydrolysate of Cynanchum bungei roots led to the isolation of eleven undescribed steroids, namely cynbungenins A-K (1-11), and seven previously described analogues (12-18). The complete structures of these compounds were elucidated using the comprehensive spectroscopic analyses and reference data. Structurally, compounds 1 and 2 represent the first example of androstane-type steroids found in the Cynanchum plants, and compounds 3-6 and 12 are characterized as pregnane-type steroids with a rare 8,14-seco-steroid core. In the cytotoxic activity assay, compound 16 displayed the strongest cytotoxic effect against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, with IC50 values of 9.98-16.42 µM, and further research indicated that it induced both apoptosis and cell cycle arrest in the G0/G1 phase in a dose-dependent manner toward HepG2 cells.

16.
Pharmacol Res ; : 107406, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278298

RESUMEN

Affinity-oriented online ligand screening with LC coupled to different detectors is widely popular to capture active compounds from herbal medicines (HMs). However, false-positive extensively occurs because insufficient information is recorded for the existence and stability of ligand-protein complex. Here, efforts were made to advance the hit confidences via configuring post-column infusion-LC-energy-resolved-affinity MS (PCI-LC-ER-AMS) to achieve "four-in-one" monitoring of: 1) response decrement of potential ligands; 2) response decrement of protein; 3) ions from ligand-protein complexes; and 4) ligand-protein binding strength. Ligand fishing for Cyt C from HMs was conducted as a proof-of-concept. For utility justification, a mimic sample containing twelve well-defined ligands and two negative controls underwent LC separation and met Cyt C prior to Qtof-MS measurements. Compared to Cyt C- or ligand-free assay, twelve ligands instead of negative controls showed response decrements that were consistent with twelve negative peaks observed at retention times corresponding to the ligands in Cyt C ion current chromatogram. Serial ions correlating to each ligand-Cyt C complex were observed. After recording breakdown graphs, optimal collision energy (OCE) corresponding to the non-covalent bond dissociation was positively correlated with binding strength. Two HMs including Scutellariae Radix (SR) and Aconiti Lateralis Radix Preparata were investigated. Consequently, 24 compounds were merely fished from SR, and particularly, flavonoid glycosides exhibited greater OCEs and also binding strengths over aglycones. Affinity assays and cellular evaluations consolidated the significant interaction between each captured compound and Cyt C. Overall, PCI-LC-ER-AMS is eligible for confidence-enhanced online ligand screening for Cyt C from HMs through "four-in-one" measurement.

17.
Cancer Lett ; : 217254, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270768

RESUMEN

As the most abundant post-transcriptional modification in eukaryotes, N6-methyladenosine (m6A) plays a crucial role in cancer cell proliferation, invasion and chemoresistance. However, its specific effects on chemosensitivity to oxaliplatin-based regimens and the impact of these drugs on m6A methylation levels in colorectal cancer (CRC) remain largely unexplored. In this study, we demonstrated that the m6A methyltransferase Wilms tumor 1-associating protein (WTAP) weakens oxaliplatin chemosensitivity in HCT116 and DLD1 cells. Mechanistically, oxaliplatin treatment upregulated WTAP expression, preventing multiple forms of cell death simultaneously, a process known as PANoptosis, by decreasing intracellular oxidative stress through maintaining the expression of nuclear factor erythroid-2-related factor 2 (NRF2), a major antioxidant response element, in an m6A-dependent manner. In addition, high WTAP expression in CRC patients is associated with a poor prognosis and reduced benefit from standard chemotherapy by clinical data analysis of the TCGA database and patient cohort study. These findings suggest that targeting WTAP-NRF2-PANoptosis axis could enhance the antitumor efficacy of oxaliplatin-based chemotherapy in CRC treatment.

18.
Chem Commun (Camb) ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258723

RESUMEN

A palladium-catalyzed coupling reaction has been developed for the generation of tertiary alkylation products by reacting olefins with diversely functionalized 1,3-dicarbonyls. The reaction involves the tertiary C-H alkylation of 1,3-dicarbonyls with olefins to produce a tertiary alcohol, followed by C-C bond cleavage.

19.
Vet J ; 308: 106228, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39243806

RESUMEN

Bovine herpesvirus 1 (BoHV-1), a significant pathogen in the alpha-herpesvirus subfamily, primarily infects cattle and causes the upper respiratory disease known as infectious bovine rhinotracheitis (IBR). In silico studies evaluated the BoHV-1 D protein to be non-allergenic, non-toxic, and highly antigenic, highlighting its potential as an antigen for vaccine development. Therefore, this study aimed to evaluate the efficacy of a subunit vaccine using the ectodomain of glycoprotein D (gD34-380) as an antigen. The truncated gD was successfully cloned and expressed in both Escherichia coli (E. coli, termed EgD) and baculovirus (termed BgD) systems, with expected molecular weights of 65 kDa and 50 kDa, respectively. For the vaccine formulation, the gD proteins were used either alone or in combination with in-house inactivated BoHV-1. Vaccination of mice and bovines showed that baculovirus-expressed gD34-380 accelerated the antibody response. Moreover, the BgD-vaccinated group also showed significantly higher neutralizing antibody levels against BoHV-1 than the control group (p<0.0001). In conclusion, our study found that BgD from BoHV-1 can increase the immune response and enhance vaccine efficacy.

20.
Int J Biol Macromol ; 279(Pt 4): 135206, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39244124

RESUMEN

Highland barley non-starch polysaccharides (HBNP), particularly ß-glucans, are known for their health-promoting effects, including modulation of glycemic response and enhancement of gut health. This study investigated the impact of different HBNP fractions on the properties and digestibility of high-glycemic index rice starch. HBNP was segmented into five fractions (HBNP-15, HBNP-30, HBNP-45, HBNP-60, and HBNP-75) using gradient ethanol precipitation, and these fractions exhibited varying molecular weights, monosaccharide compositions, and ß-glucan contents. All fractions reduced rice starch's pasting viscosity, with 1 % HBNP-75 leading to a 99.1 % decrease in final viscosity. Morphological and size distribution analyses showed that HBNP fractions limited granule swelling and disrupted starch's continuous phase structure. HBNPs also reduced starch digestibility and increased the formation of resistant starch from 10 % to 28 %. These results suggest potential uses for HBNP fractions in developing low-glycemic starch-based foods.

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