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1.
Front Pharmacol ; 15: 1396975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725666

RESUMEN

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

2.
Cancer Lett ; : 216953, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729557

RESUMEN

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

3.
Cancer Cell ; 42(5): 727-731, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38701791

RESUMEN

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Inmunoterapia/métodos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Biomarcadores de Tumor/genética , Terapia Neoadyuvante/métodos , Ensayos Clínicos como Asunto
4.
J Colloid Interface Sci ; 669: 275-282, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38718581

RESUMEN

The triboelectric nanogenerator (TENG) of natural biomaterials is a new type of energy harvesting device and can be used as a self-powered sensor, which has received extensive research and attention. In this paper, based on the biocompatibility of chitosan and chondroitin sulfate, ZnO-modified chitosan/chondroitin sulfate/ZnO TENG was prepared for research on wearable devices and sustainable power supply devices. This study employs molecular dynamics to compute the interaction energy between chitosan and ZnO molecules. Theoretical calculations have unequivocally substantiated the occurrence of a binding interaction between these two molecular entities. The effect of ZnO on chitosan/chondroitin sulfate morphology was investigated by atomic force microscopy. The chitosan/chondroitin sulfate/ZnO TENG has high flexibility and electrical output performance. It can reach 105 V and 3.3 µA of open-circuit voltage and short-circuit current. Chitosan/chondroitin Sulfate/ZnO TENG successfully converts the mechanical energy of human motion into electrical energy. Strong electrical signals are exhibited when making fists and waving fingers and wrists. The TENG is a self-powered source and lights up 70 blue light-emitting diodes (LEDs). The chitosan/chondroitin sulfate/ZnO TENG has demonstrated its capabilities in energy harvesting and wearable self-powered sensors.

5.
Int J Ophthalmol ; 17(3): 528-536, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721515

RESUMEN

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

6.
Heart Lung ; 67: 53-61, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38701700

RESUMEN

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

7.
Toxics ; 12(4)2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38668486

RESUMEN

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

8.
Sensors (Basel) ; 24(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38676098

RESUMEN

This paper designed and developed an online digital imaging excitation sensor for wind power gearbox wear condition monitoring based on an adaptive deep learning method. A digital imaging excitation sensing image information collection architecture for magnetic particles in lubricating oil was established to characterize the wear condition of mechanical equipment, achieving the real-time online collection of wear particles in lubricating oil. On this basis, a mechanical equipment wear condition diagnosis method based on online wear particle images is proposed, obtaining data from an engineering test platform based on a wind power gearbox. Firstly, a foreground segmentation preprocessing method based on the U-Net network can effectively eliminate the interference of bubbles and dark fields in online wear particle images, providing high-quality segmentation results for subsequent image processing, A total of 1960 wear particle images were collected in the experiment, the average intersection union ratio of the validation set is 0.9299, and the accuracy of the validation set is 0.9799. Secondly, based on the foreground segmentation preprocessing of wear particle images, by using the watered algorithm to obtain the number of particles in each size segment, we obtained the number of magnetic particle grades in three different ranges: 4-38 µm, 39-70 µm, and >70 µm. Thirdly, we proposed a method named multidimensional transformer (MTF) network. Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE) are used to obtain the error, and the maintenance strategy is formulated according to the predicted trend. The experimental results show that the predictive performance of our proposed model is better than that of LSTM and TCN. Finally, the online real-time monitoring system triggered three alarms, and at the same time, our offline sampling data analysis was conducted, the accuracy of online real-time monitoring alarms was verified, and the gearbox of the wind turbine was shut down for maintenance and repair.

9.
Int J Biol Macromol ; 268(Pt 2): 131721, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38649079

RESUMEN

Interferon (IFN) alpha/beta receptor 1 (IFNAR1) is indispensable for antiviral responses and the immune regulation. Dysregulation of the IFNAR1-mediaetd signaling pathways leads to deleterious autoimmune diseases such as systemic lupus erythematosus (SLE). QX006N, a humanized therapeutic monoclonal antibody, specifically targets human IFNAR1 and is in the clinical trial phase for treating SLE, but the molecular mechanism underlying the QX006N-mediated recognition of IFNAR1 remains unclear. Here, we report the high neutralization activities of QX006N against IFNAR1-mediated signal transduction. Meanwhile, we determine the structures of the fragment antigen-binding domain (Fab) of QX006N (QX006N-Fab) and QX006N-Fab in complex with the subdomains 1-3 of IFNAR1 (IFNAR1-SD123) at 2.87 Å and 2.68 Å resolutions, respectively. In the structure of the QX006N-Fab/IFNAR1-SD123 complex, QX006N-Fab only recognizes the SD3 subdomain of IFNAR1 by the hydrophobic, hydrogen-bonding and electrostatic interactions. Compared with the structure of the IFN/IFNAR1/IFNAR2 complex, the binding of QX006N-Fab to IFNAR1-SD3 blocks its association with IFN due to steric hindrance, which inhibits the IFN/IFNAR1/IFNAR2 complex formation for signal transduction. The results of this study provide the structural evidence for the specific targeting of IFNAR1 by the therapeutic antibody QX006N and pave the way for the rational design of antibody drugs to combat IFNAR1-related autoimmune diseases.

10.
Int Immunopharmacol ; 132: 111970, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38608472

RESUMEN

OBJECTIVES: As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear. METHODS: Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury. RESULTS: Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex. CONCLUSION: NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.


Asunto(s)
Apoptosis , ADN Mitocondrial , Células Asesinas Naturales , Moxifloxacino , Moxifloxacino/farmacología , Humanos , Apoptosis/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Adulto , Células Cultivadas , Citocinas/metabolismo , Antibacterianos/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Masculino
11.
Phytochemistry ; 222: 114098, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38648960

RESUMEN

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.


Asunto(s)
Péptidos beta-Amiloides , Apoptosis , Microglía , Simulación del Acoplamiento Molecular , Fragmentos de Péptidos , Microglía/efectos de los fármacos , Microglía/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Fragmentos de Péptidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Ratones , Estructura Molecular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Lentinula/química , Línea Celular
12.
Tissue Cell ; 88: 102390, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38663113

RESUMEN

Despite advancements in medical care, the management of bone injuries remains one of the most significant challenges in the fields of medicine and sports medicine globally. Bone tissue damage is often associated with aging, reduced quality of life, and various conditions such as trauma, cancer, and infection. While bone tissue possesses the natural capacity for self-repair and regeneration, severe damage may render conventional treatments ineffective, and bone grafting may be limited due to secondary surgical procedures and potential disease transmission. In such cases, bone tissue engineering has emerged as a viable approach, utilizing cells, scaffolds, and growth factors to repair damaged bone tissue. This research shows a comprehensive review of the current literature on the most important and effective methods and materials for improving the treatment of these injuries. Commonly employed cell types include osteogenic cells, embryonic stem cells, and mesenchymal cells, while scaffolds play a crucial role in bone tissue regeneration. To create an effective bone scaffold, a thorough understanding of bone structure, material selection, and examination of scaffold fabrication techniques from inception to the present day is necessary. By gaining insights into these three key components, the ability to design and construct appropriate bone scaffolds can be achieved. Bone tissue engineering scaffolds are evaluated based on factors such as strength, porosity, cell adhesion, biocompatibility, and biodegradability. This article examines the diverse categories of bone scaffolds, the materials and techniques used in their fabrication, as well as the associated merits and drawbacks of these approaches. Furthermore, the review explores the utilization of various scaffold types in bone tissue engineering applications.

14.
Fitoterapia ; 175: 105960, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621426

RESUMEN

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

15.
Front Vet Sci ; 11: 1364740, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601912

RESUMEN

Background: Mosquito-borne diseases pose serious public health threats in Zhejiang Province, China, and vector control is believed to be the primary method for reducing transmission. Due to severe resistance problems, effective and sustainable methods without chemical insecticides are urgently required to control mosquito vectors. Attractive toxic sugar baits (ATSB) are newly developed methods to control mosquitoes in recent decades with the core element sugar bait, which was invented according to the sugar-feeding behavior of mosquitoes. In this study, we developed a Novel Sugar Bait Device (NSBD) trap by combining sugar bait and physical adhesive capture technology. The study aimed to evaluate the effect of the NSBD trap on controlling mosquitoes in residential environments and to identify the optimal sugar solution concentration in the sugar bait of the NSBD for real use. Methods: Four residential villages in Ningbo City with similar geographic environments and mosquito densities were selected for field trials in 2022. One village (site 1) was designated as the control group, and three villages (sites 2-4) served as the test groups to assess the effectiveness of NSBD traps with different sugar solution concentrations (6, 8, and 10%) in the sugar bait. Larval and adult mosquito densities were monitored monthly before and semi-monthly after the trials using the CDC light trap and larval pipette method. Results: Before the trials, we monitored mosquito density for 3 months to confirm the baseline mosquito density among the four sites, and no statistical differences in adult and larval mosquitoes were found (adult, F = 3.047, p > 0.05; larvae, F = 0.436, p > 0.05). After the trials, all NCBD traps effectively controlled larval and adult mosquito densities, with the highest standard decrease rates of larval and adult mosquito densities at 57.80 and 86.31%, respectively, observed in site 4. The most suitable sugar solution concentration in the sugar bait was 10%. Conclusion: NSBD traps effectively controlled mosquitoes in residential environments during field trials. Without the use of insecticides, this may be a promising choice for mosquito vector control to prevent mosquito-borne diseases.

16.
ACS Appl Mater Interfaces ; 16(15): 19167-19174, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38569197

RESUMEN

Ultraviolet photodetectors (UV PDs) have attracted significant attention due to their wide range of applications, such as underwater communication, biological analysis, and early fire warning systems. Indium oxide (In2O3) is a candidate for developing high-performance photoelectrochemical (PEC)-type UV PDs owing to its high UV absorption and good stability. However, the self-powered photoresponse of the previously reported In2O3-based PEC UV PDs is unsatisfactory. In this work, high-performance self-powered PEC UV PDs were constructed by using an In2O3 nanocube film (NCF) as a photoanode. In2O3 NCF photoanodes were synthesized on FTO by using hydrothermal methods with a calcining process. The influence of the electrolyte concentration, bias potential, and irradiation light on the photoresponse properties was systematically studied. In2O3 NCF PEC UV PDs exhibit outstanding self-powered photoresponses to 365 nm UV light with a high responsivity of 44.43 mA/W and fast response speed (20/30 ms) under zero bias potential, these results are superior to those of previously reported In2O3-based PEC UV PDs. The improved self-powered photoresponse is attributed to the higher photogenerated carrier separation efficiency and faster charge transport of the in-situ grown In2O3 NCF. In addition, these PDs exhibit excellent multicycle stability, maintaining the photocurrent at 98.69% of the initial value after 700 optical switching cycles. Therefore, our results prove the great promise of In2O3 in self-powered PEC UV PDs.

17.
Pediatr Surg Int ; 40(1): 106, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613719

RESUMEN

PURPOSE: To explore the influence of postoperative Hirschsprung-associated enterocolitis (post-HAEC) on long-term outcomes and to identify risk factors of post-HAEC. METHODS: The medical records of 304 eligible patients diagnosed with Hirschsprung's disease (HSCR) were reviewed. We analyzed the clinical characteristics of post-HAEC and its influence on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were identified separately. RESULTS: The overall incidence of post-HAEC was 29.9% (91/304). We categorized early HAEC as occurring within postoperative 3 months (n = 39) and recurrent HAEC as occurring ≥ 3 episodes within postoperative 6 months (n = 25). Patients with early HAEC were more likely to experience worse nutritional status, defecation function, and quality of life compared to those with late or no episodes (P < 0.05). Similarly, the adverse influences of recurrent HAEC on these outcomes were also significant (P < 0.05). The risk factors for early HAEC included preoperative undernutrition, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. For recurrent HAEC, risk factors were preoperative malnutrition, non-parental caregivers, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. CONCLUSION: Classification of post-HAEC based on the first episode time and frequency was necessary. The earlier or more frequent episodes of post-HAEC have detrimental influences on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were different.


Asunto(s)
Enterocolitis , Enfermedad de Hirschsprung , Desnutrición , Niño , Humanos , Estudios Retrospectivos , Calidad de Vida , Enterocolitis/epidemiología , Enterocolitis/etiología , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/cirugía , Complicaciones Posoperatorias/epidemiología , Centros de Atención Terciaria
18.
Int J Surg ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38626442

RESUMEN

BACKGROUND: The ongoing debate regarding off-pump CABG and on-pump CABG has endured for over three decades. Although numerous randomized controlled trials (RCTs) and meta-analyses have been reported, new evidence has emerged. Therefore, an updated and comprehensive meta-analysis to guide clinical practice is essential. MATERIALS AND METHODS: A comprehensive search for eligible articles published after 2000, reporting RCTs involving at least 100 patients and comparing off-pump CABG with on-pump CABG, was performed throughout the databases including Embase, Ovid Medline and Web of Science. The primary interested outcomes included the short-term incidence of stroke and long-term mortality. The primary analysis utilized Fixed-effect model with the inverse variance method. The Grade of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. RESULTS: After thorough screening, 39 articles were included, consisting of 28 RCTs and involving a total of 16090 patients. Off-pump CABG significantly reduced the incidence of short-term stroke (1.27% vs. 1.78%, OR: 0.74, P=0.03, high certainty). However, it was observed to be associated with increased mid-term coronary reintervention (2.77% vs. 1.85%, RR: 1.49, P<0.01, high certainty) and long-term mortality (21.8% vs. 21.0%, RR: 1.09, P=0.02, moderate certainty). CONCLUSIONS: Off-pump CABG significantly reduces the short-term incidence of stroke, but it also increases the incidence of mid-term coronary reintervention. Moreover, it may increase long-term mortality.

19.
Signal Transduct Target Ther ; 9(1): 80, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565536

RESUMEN

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.


Asunto(s)
Neoplasias Colorrectales , ARN Circular , Humanos , Autofagia/genética , Neoplasias Colorrectales/metabolismo , Familia , Fosfoproteínas/metabolismo , Proteínas/metabolismo , ARN/genética , ARN Circular/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
20.
Front Cardiovasc Med ; 11: 1360648, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685980

RESUMEN

Background: The angiography-derived index of microvascular resistance (A-IMR) is a novel tool for diagnosing coronary microvascular dysfunction (CMD) addressing limitation of unavailability. However, the clinical value of A-IMR remains controversial. Methods: A systematic review and meta-analysis was conducted. PubMed, EMBASE, Cochrane Library and Web of Science were searched for relevant studies. Studies that reported estimates of A-IMR's diagnostic accuracy (with thermodilution-based IMR as the reference test) and/or predictions of adverse cardiovascular events were selected. Pooled sensitivity, specificity, area under the summary receiver operating characteristic curve (sROC) were calculated to measure diagnostic performance; pooled hazard/risk ratio (HR/RR) and 95% confidence interval (95% CI) of major adverse cardiovascular events (MACE) or other independent adverse events were calculated to measure prognostic effect. This study was registered with PROSPERO (CRD42023451884). Results: A total of 12 diagnostic studies pooling 1,642 vessels and 12 prognostic studies pooling 2,790 individuals were included. A-IMR yielded an area under sROC of 0.93 (95% CI: 0.91, 0.95), a pooled sensitivity of 0.85 (95% CI: 0.79, 0.89) and a pooled specificity of 0.89 (95% CI: 0.83, 0.93) for the diagnosis of CMD. CMD diagnosed using A-IMR was associated with higher risks of MACE (HR, 2.73, 95% CI: 2.16, 3.45), CV death (RR, 2.39, 95% CI: 1.49, 3.82) and heart failure hospitalization (HR, 2.30, 95% CI: 1.53, 3.45). Conclusion: A-IMR demonstrated high diagnostic accuracy for CMD and showed a strong prognostic capability in predicting the risk of adverse CV outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451884, PROSPERO (CRD42023451884).

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