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2.
Asian Spine J ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764226

RESUMEN

Study Design: A retrospective analysis. Purpose: To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP). Overview of Literature: RBP is a vexing complication that affects 6.3%-17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients' psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication. Methods: Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Results: Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05). Conclusions: Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.

3.
Nat Commun ; 15(1): 4347, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773146

RESUMEN

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.


Asunto(s)
Desmetilasa de ARN, Homólogo 5 de AlkB , Astrocitos , Trastorno Depresivo Mayor , Ratones Noqueados , Animales , Astrocitos/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Ratones , Humanos , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/patología , Masculino , Femenino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Neuronas/metabolismo , Estrés Psicológico/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Conducta Animal , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Depresión/metabolismo , Depresión/genética , Adulto , Transmisión Sináptica , Persona de Mediana Edad
4.
Front Pharmacol ; 15: 1345380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751789

RESUMEN

Periprosthetic osteolysis (PPO) is the most common cause of joint arthroplasty failure. Its progression involves both biological and mechanical factors. Osteoclastogenesis induced by wear from debris-cell interactions, ultimately leading to excessive bone erosion, is considered the primary cause of PPO; therefore, targeting osteoclasts is a promising treatment approach. Currently available drugs have various side effects and limitations. Artemisinic acid (ArA) is a sesquiterpene isolated from the traditional herb Artemisia annua L. that has various pharmacological effects, such as antimalarial, anti-inflammatory, and antioxidant activities. Therefore, this study was aimed at investigating the effect of ArA on osteoclast formation and bone resorption function in vitro, as well as wear particle-induced osteolysis in vivo, and to explore its molecular mechanism of action. Here, we report that ArA inhibits RANKL-stimulated osteoclast formation and function. Mechanistically, ArA suppresses intracellular reactive oxygen species levels by activating the antioxidant response via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway upregulation. It also inhibits the mitogen-activated kinases (MAPK) and nuclear factor-κB (NF-κB) pathways, as well as the transcription and expression of NFATc1 and c-Fos. In vivo experiments demonstrated that ArA reduces osteoclast formation and alleviates titanium particle-induced calvarial osteolysis. Collectively, our study highlights that ArA, with its osteoprotective and antioxidant effects, is a promising therapeutic agent for preventing and treating PPO and other osteoclast-mediated osteolytic diseases.

5.
Adv Healthc Mater ; : e2401103, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691848

RESUMEN

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, low back pain imposes a significant global economic burden. However, the effectiveness of treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective IVDD treatments by focusing on oxidative stress as a starting point. In this study, an injectable reactive oxygen species-responsive hydrogel (PVA-tsPBA@SLC7A11 modRNA) is developed, designed to achieve rapid loading and selective release of chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA is specifically used to upregulate the expression of the ferroptosis marker SLC7A11. The local injection of PVA-tsPBA@SLC7A11 modRNA into the degenerated intervertebral disc (IVD) results in the cleavage of PVA-tsPBA, leading to the release of enclosed SLC7A11 modRNA. The extent of SLC7A11 modRNA release is directly proportional to the severity of IVDD, ultimately ameliorating IVDD by inhibiting ferroptosis in nucleus pulposus cells (NPCs). This study proposes an innovative system of PVA-tsPBA hydrogel-encapsulated modRNA, representing a potential novel treatment strategy for patients with early-stage IVDD.

6.
Bioact Mater ; 37: 459-476, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38698920

RESUMEN

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38568073

RESUMEN

A novel bacterial strain, designated WL0086T, was isolated from a marine sediment sample collected in Lianyungang city, Jiangsu province, PR China. This strain showed the highest 16S rRNA gene sequence similarity to Geminisphaera colitermitum TAV2T (92.7 %) of the family Opitutaceae, and all the unclassified cultured and uncultured isolates with similarities >95 % were from marine environments. Cells were Gram-stain-negative, aerobic, non-motile cocci with a size of 0.6-0.8 µm in diameter. Strain WL0086T was positive for both oxidase and catalase, and grew at 20-37 °C (optimum, 28 °C), with 1.5-11.0 % NaCl (w/v; optimum, 2.5-4.0 %) and at pH 5.0-9.0 (optimum, pH 7.0). The major polar lipid profile of strain WL0086T consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylcholine. The major isoprenoid quinone was menaquinone-7 and the predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0 and C16 : 1 ω9c. The complete genome consisted of a chromosome with 6 109 182 bp. The G+C content of genomic DNA was 64.0%. Results of phylogenomic analysis based on the 16S rRNA gene sequence and the whole genome suggested that strain WL0086T formed a distinct clade closely neighbouring the members of the family Opitutaceae. On the basis of phylogenetic, phenotypic, and chemotaxonomic evidences, strain WL0086T should represent a novel genus of the family Opitutaceae, for which the name Actomonas aquatica gen. nov., sp. nov. is proposed. The type strain is WL0086T (=MCCC 1K05844T=JCM 34677T=GDMCC 1.2411T).


Asunto(s)
Carbono , Fijación del Nitrógeno , Composición de Base , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana
8.
Methods Mol Biol ; 2794: 341-351, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38630243

RESUMEN

Single-cell RNA sequencing (scRNA-seq) has been widely applied in neuroscience research, enabling the investigation of cellular heterogeneity at the transcriptional level, the characterization of rare cell types, and the detailed analysis of the stochastic nature of gene expression. Isolation of single nerve cells in good health, especially from the adult rodent brain, is the most difficult and critical process for scRNA-seq. Here, we describe methods to optimize protease digestion of brain slices, which enable yield of millions of cells in good health from the adult brain.


Asunto(s)
Astrocitos , Neuronas , Animales , Ratones , RNA-Seq , Encéfalo , Endopeptidasas , Suspensiones
9.
Ying Yong Sheng Tai Xue Bao ; 35(3): 577-586, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38646744

RESUMEN

The analytical equation based on Monin-Obukhov (M-O) similarity theory (i.e., wind profile equation) has been adopted since 1970s for using in the prediction of wind vertical profile over flat terrains, which is mature and accurate. However, its applicability over complex terrains remains unknown. This applicability signifies the accuracy of the estimations of aerodynamic parameters for the boundary layer of non-flat terrain, such as zero-displacement height (d) and aerodynamic roughness length (z0), which will determine the accuracy of frequency correction and source area analysis in calculating carbon, water, and trace gas fluxes based on vorticity covariance method. Therefore, the validation of wind profile model in non-flat terrain is the first step to test whether the flux model needs improvement. We measured three-dimensional wind speed data by using the Ker Towers (three towers in a watershed) at Qingyuan Forest CERN in the Mountainous Region of east Liaoning Province, and compared them with data from Panjin Agricultural Station in the Liaohe Plain, to evaluate the applicability of a generalized wind profile model based on the Monin-Obukhov similarity theory on non-flat terrain. The results showed that the generalized wind profile model could not predict wind speeds accurately of three flux towers separately located in different sites, indicating that wind profile model was not suitable for predicting wind speeds in complex terrains. In the leaf-off and leaf-on periods, the coefficient of determination (R2) between observed and predicted wind speeds ranged from 0.12 to 0.30. Compared to measured values, the standard error of the predicted wind speeds was high up to 2 m·s-1. The predicted wind speeds were high as twice as field-measured wind speed, indicating substantial overestimation. Nevertheless, this model correctly predicted wind speeds in flat agricultural landscape in Panjin Agricultural Station. The R2 between observed wind speeds and predicted wind speed ranged from 0.90 to 0.93. The standard error between observed and predicted values was only 0.5 m·s-1. Results of the F-test showed that the root-mean-square error of the observed and predicted wind speeds in each secondary forest complex terrain was much greater than that in flat agricultural landscape. Terrain was the primary factor affecting the applicability of wind profile model, followed by seasonality (leaf or leafless canopy). The wind profile model was not applicable to the boundary-layer flows over forest canopies in complex terrains, because the d was underestimated or both the d and z0 were underestimated, resulting in inaccurate estimation of aerodynamic height.


Asunto(s)
Bosques , Modelos Teóricos , Viento , China , Árboles/crecimiento & desarrollo , Monitoreo del Ambiente/métodos , Ecosistema , Altitud
10.
Food Chem X ; 22: 101377, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38633741

RESUMEN

In this study, the effects on the structures and emulsion gels of carrageenan (CA) and gum arabic (GA) with soybean protein isolate (SPI) were investigated. The results showed that CA and GA exposed hydrophobic groups to SPI, and formed complexes through non-covalent interactions to improve the stability of the complexes. Furthermore, the emulsion gels based on the emulsions exhibited that CA formed emulsion-filled gels with higher elasticity, stronger gel strength, and thermal reversibility, whereas GA formed emulsion-aggregated gels with higher viscosity, and a weak-gel network. The results of digestion showed that, CA was more helpful to slow down the release of free fatty acids and protect vitamin E during digestion. Compared with SPI-GA emulsion gel, SPI-CA emulsion gel had better physicochemical properties and stronger network structure. The results of this study may be useful in the development of anionic polysaccharides that interact with SPI, and they may provide new insights on the preparation of emulsion gels that slowly release fat-soluble nutrients.

11.
Front Neurosci ; 18: 1364409, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680447

RESUMEN

Deformable registration plays a fundamental and crucial role in scenarios such as surgical navigation and image-assisted analysis. While deformable registration methods based on unsupervised learning have shown remarkable success in predicting displacement fields with high accuracy, many existing registration networks are limited by the lack of multi-scale analysis, restricting comprehensive utilization of global and local features in the images. To address this limitation, we propose a novel registration network called multi-scale feature extraction-integration network (MF-Net). First, we propose a multiscale analysis strategy that enables the model to capture global and local semantic information in the image, thus facilitating accurate texture and detail registration. Additionally, we introduce grouped gated inception block (GI-Block) as the basic unit of the feature extractor, enabling the feature extractor to selectively extract quantitative features from images at various resolutions. Comparative experiments demonstrate the superior accuracy of our approach over existing methods.

12.
Biol Psychiatry ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679359

RESUMEN

Neuronal activity is the basis of information encoding and processing in the brain. During neuronal activation, intracellular ATP is generated to meet the high-energy demands. Meantime, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell‒cell communication to prevent aberrant hyperexcitability of the nervous system. In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological aspects, such as sleep and wakefulness, learning and memory, and feeding. Dysregulation of extracellular ATP leads to a "destabilizing" effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder. This review summarizes advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks. In particular, we also focus on neural activity issues resulting from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases. Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

13.
Cell Rep Med ; : 101513, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38608697

RESUMEN

Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.

14.
ACS Appl Mater Interfaces ; 16(17): 21383-21399, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626424

RESUMEN

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1ß-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.


Asunto(s)
Factores de Transcripción Activadores , Condrocitos , Exosomas , Mitocondrias , Osteoartritis , ARN Mensajero , Respuesta de Proteína Desplegada , Osteoartritis/patología , Osteoartritis/metabolismo , Osteoartritis/terapia , Exosomas/metabolismo , Exosomas/química , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Factores de Transcripción Activadores/metabolismo , Factores de Transcripción Activadores/química , Factores de Transcripción Activadores/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Humanos , Células Madre Mesenquimatosas/metabolismo , Hidrogeles/química , Masculino , Cartílago Articular/metabolismo , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos
15.
Food Chem ; 451: 139221, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38688094

RESUMEN

This study aimed to explore the changes in the structural and functional properties of cornstarch modified by oxidation, esterification, and cross-linking under ultrasonic pretreatment. FT-IR and XRD characteristic peaks revealed successful access to chemical functional groups. Both ultrasonic and the three chemical treatments eroded the surface of starch granules, reducing their particle size and increasing their RC. Meanwhile, the destruction of the granules was further enhanced by the dual modification treatments. The ultrasonic pretreatment synergized and improved the swelling power, solubility, and translucency of all three chemical treatments. Further, it improved the poorer freeze-thaw stability of cross-linked starch, resulting in a lower water precipitation rate. In addition, both ultrasonic and chemical treatments significantly decreased RDS and SDS, and increased RS content. The ultrasonic-chemical dual modification had a synergistic effect on in vitro digestibility, resulting in a further increase in RS. In conclusion, this study provided ideas for developing new starch modification technology and deep processing of cornstarch, expanding its application areas and thus meeting the different needs of starch-based products.

16.
Sci Rep ; 14(1): 5147, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429352

RESUMEN

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat.


Asunto(s)
Óxido de Aluminio , Silicatos de Aluminio , Cucumis sativus , Cucurbitaceae , Oryza , Dióxido de Silicio , Carbohidratos de la Dieta , Suelo
17.
Front Oncol ; 14: 1336375, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500660

RESUMEN

Background: Bladder cancer stands as the predominant malignant tumor in the urological system, presenting a significant challenge to public health and garnering extensive attention. Recently, with the deepening research into tumor molecular mechanisms, non-coding RNAs (ncRNAs) have emerged as potential biomarkers offering guidance for the diagnosis and prognosis of bladder cancer. However, the definitive role of ncRNAs in bladder cancer remains unclear. Hence, this study aims to elucidate the relevance and significance of ncRNAs through a Meta-analysis. Methods: A systematic meta-analysis was executed, including studies evaluating the diagnostic performance of ncRNAs and their associations with overall survival (OS) and disease-free survival (DFS). Key metrics such as hazard ratios, sensitivity, specificity, and diagnostic odds ratios were extracted and pooled from these studies. Potential publication bias was assessed using Deeks' funnel plot, and the robustness of the results was ascertained through a sensitivity analysis. Results: Elevated ncRNA expression showed a positive correlation with improved OS, evidenced by a hazard ratio (HR) of 0.82 (95% CI: 0.66-0.96, P<0.001). Similarly, a significant association was observed between heightened ncRNA expression and DFS, with an HR of 0.86 (95% CI: 0.73-0.99, P<0.001). Diagnostic performance analysis across 17 articles yielded a pooled sensitivity of 0.76 and a specificity of 0.83. The diagnostic odds ratio was recorded at 2.71, with the area under the ROC curve (AUC) standing at 0.85. Conclusion: Exosome ncRNAs appear to possess potential significance in the diagnostic and prognostic discussions of bladder cancer. Their relationship with survival outcomes and diagnostic measures suggests a possible clinical utility. Comprehensive investigations are needed to fully determine their role in the ever-evolving landscape of bladder cancer management, especially within the framework of personalized medicine.

18.
Am J Cancer Res ; 14(2): 809-831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455406

RESUMEN

Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo. By using Chromatin immunoprecipitation (ChIP) assay, it was demonstrated that the transcription factor Yin Yang 1 (YY1) is capable of binding to the LINC00511 promoter and enhancing its expression in cis. Further mechanistic investigation showed that LINC00511 was mainly enriched in the cytoplasm of melanoma cells and interacted directly with microRNA-150-5p (miR-150-5p). Consistently, the knockdown of miR-150-5p could recover the effects of LINC00511 knockdown on melanoma cells. Furthermore, ADAM metallopeptidase domain expression 19 (ADAM19) was identified as a downstream target of miR-150-5p, and overexpression of ADAM19 could promote melanoma cell proliferation. Rescue assays indicated that LINC00511 acted as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and increase the expression of ADAM19, thereby activating the PI3K/AKT pathway. In summary, we identified LINC00511 as an oncogenic lncRNA in melanoma and defined the LINC00511/miR-150-5p/ADAM19 axis, which might be considered a potential therapeutic target and novel molecular mechanism the treatment of patients with melanoma.

19.
Front Neurosci ; 18: 1364338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486967

RESUMEN

In clinical practice and research, the classification and diagnosis of neurological diseases such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA) have long posed a significant challenge. Currently, deep learning, as a cutting-edge technology, has demonstrated immense potential in computer-aided diagnosis of PD and MSA. However, existing methods rely heavily on manually selecting key feature slices and segmenting regions of interest. This not only increases subjectivity and complexity in the classification process but also limits the model's comprehensive analysis of global data features. To address this issue, this paper proposes a novel 3D context-aware modeling framework, named 3D-CAM. It considers 3D contextual information based on an attention mechanism. The framework, utilizing a 2D slicing-based strategy, innovatively integrates a Contextual Information Module and a Location Filtering Module. The Contextual Information Module can be applied to feature maps at any layer, effectively combining features from adjacent slices and utilizing an attention mechanism to focus on crucial features. The Location Filtering Module, on the other hand, is employed in the post-processing phase to filter significant slice segments of classification features. By employing this method in the fully automated classification of PD and MSA, an accuracy of 85.71%, a recall rate of 86.36%, and a precision of 90.48% were achieved. These results not only demonstrates potential for clinical applications, but also provides a novel perspective for medical image diagnosis, thereby offering robust support for accurate diagnosis of neurological diseases.

20.
RSC Adv ; 14(8): 5627-5637, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38352672

RESUMEN

To fabricate a two-electrode flexible pH sensor based on polypropylene spunbonded nonwoven fabric (PP SF), oily polyurethane (OPU) was first coated on the surface of PP SF to obtain OPU/PP SF. Then, silver/silver chloride (Ag/AgCl) paste, used as the reference electrode and conductive carbon (C) paste were transferred to the OPU/PP SF surface through screen printing. Polyaniline (PANI) was deposited on the surface of the C paste to form a sensing working electrode via the electro-chemical deposition method. The results showed that the surface of the obtained PANI@OPU/PP SF flexible pH sensor (3D PANI pH sensor) presented a three-dimensional (3D) porous network structure. The 3D PANI pH sensor had good mechanical properties, an excellent Nernst response (-67.67 mV pH-1) and linearity (R2 = 0.99) in the pH range from 2.00 to 8.00 in the normal state. In the bent state, the 3D PANI pH sensor retained similar sensitivity (-68.87 mV pH-1) and linearity (R2 = 0.99). Moreover, the 3D PANI pH sensor exhibited a short response time (8 s), excellent reversibility (1.20 mV), low temperature drift (-0.0872 mV pH-1 °C-1) and long-term stability (0.83 mV h-1) in the normal state. Furthermore, the 3D PANI pH sensor can be effectively applied for pH monitoring of liquids and fruits with irregular curved surfaces. The error margin is no more than 0.16 compared to a commercial pH meter.

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