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1.
Chemosphere ; 363: 142835, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38996981

RESUMEN

Color vision, initiated from the cone photoreceptors, is essential for fish to obtain environmental information. Although the visual impairment of triazine herbicide prometryn has been reported, data on the effect of herbicide such as prometryn on natural color sensitivity of fish is scarce. Here, zebrafish were exposed to prometryn (0, 1, 10, and 100 µg/L) from 2 h post-fertilization to 160 days post-fertilization, to explore the effect and underlying mechanism of prometryn on color perception. The results indicated that 10 and 100 µg/L prometryn shortened the height of red-green cone cells, and down-regulated expression of genes involved in light transduction pathways (arr3a, pde6h) and visual cycle (lrata, rpe65a); meanwhile, 1 µg/L prometryn increased all-trans-retinoic acid levels in zebrafish eyes, and up-regulated the expression of genes involved in retinoid metabolism (rdh10b, aldh1a2, cyp26a1), finally leading to weakened red and green color perception of female zebrafish. This study first clarified how herbicide such as prometryn affected color vision of a freshwater fish after a long-term exposure from both morphological and functional disruption, and its hazard on color vision mediated-ecologically relevant tasks should not be ignored.

2.
Sci Adv ; 10(26): eadk2913, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941455

RESUMEN

The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.


Asunto(s)
Astrocitos , Barrera Hematoencefálica , Células Endoteliales , Mitocondrias , Astrocitos/metabolismo , Barrera Hematoencefálica/metabolismo , Animales , Mitocondrias/metabolismo , Ratones , Células Endoteliales/metabolismo , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética
3.
Signal Transduct Target Ther ; 9(1): 124, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744846

RESUMEN

Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.


Asunto(s)
Mitocondrias , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/terapia , Enfermedades Mitocondriales/metabolismo , ADN Mitocondrial/genética , MicroARNs/genética , Neoplasias/genética , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/terapia , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Animales
4.
Artículo en Inglés | MEDLINE | ID: mdl-38591204

RESUMEN

BACKGROUND: Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. OBJECTIVE: This study aims to identify potential gene markers for inguinal hernia and available drugs. METHODS: Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. RESULTS: The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). CONCLUSION: We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.

5.
Nat Commun ; 15(1): 2529, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514612

RESUMEN

Transcortical vessels (TCVs) provide effective communication between bone marrow vascular system and external circulation. Although osteocytes are in close contact with them, it is not clear whether osteocytes regulate the homeostasis of TCVs. Here, we show that osteocytes maintain the normal network of TCVs by transferring mitochondria to the endothelial cells of TCV. Partial ablation of osteocytes causes TCV regression. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. By contrast, acquisition of osteocyte mitochondria by endothelial cells efficiently restores endothelial dysfunction. Administration of osteocyte mitochondria resultes in acceleration of the angiogenesis and healing of the cortical bone defect. Our results provide new insights into osteocyte-TCV interactions and inspire the potential application of mitochondrial therapy for bone-related diseases.


Asunto(s)
Angiogénesis , Osteocitos , Osteocitos/metabolismo , Células Endoteliales , Huesos , Mitocondrias
6.
Ecotoxicol Environ Saf ; 274: 116203, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38479313

RESUMEN

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.


Asunto(s)
Contaminantes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Adulto , Niño , Humanos , Residuos Sólidos , Monitoreo del Ambiente/métodos , Dibenzodioxinas Policloradas/toxicidad , Dibenzodioxinas Policloradas/análisis , Dibenzofuranos , Contaminantes Atmosféricos/análisis , Incineración , Dioxinas/toxicidad , Medición de Riesgo , Dibenzofuranos Policlorados/análisis , Suelo
7.
Water Res ; 254: 121350, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38402752

RESUMEN

Redox condition is an important controlling factor for contaminant removal in constructed wetlands; however, the redox-sensitivity of antibiotic removal in wetland sediments under controlled conditions with specific electron acceptors remains unclear. Here, using a 14C radioactive tracer, we explored fate of sulfamethoxazole (SMX) in a wetland sediment slurry under oxic, nitrate-reducing, iron-reducing, and methanogenic conditions. In the sterile treatment, unlike the comparable SMX dissipation from the water phase under four redox conditions, non-extractable residues (NERs) of SMX was highest formed in the sediment under oxic condition, mainly in sequestered and ester/amide-linked forms. Microorganisms markedly promoted SMX transformation in the slurry. The dissipation rate of SMX and its transformation products (TPs) followed the order: oxic ≈ iron-reducing > methanogenic >> nitrate-reducing conditions, being consistent with the dynamics of microbial community in the sediment, where microbial diversity was greater and networks connectivity linking dominant bacteria to SMX transformation were more complex under oxic and iron-reducing conditions. Kinetic modeling indicated that the transformation trend of SMX and its TPs into the endpoint pool NERs depended on the redox conditions. Addition of wetland plant exudates and sediment dissolved organic matter at environmental concentrations affected neither the abiotic nor the biotic transformation of SMX. Overall, the iron-reducing condition was proven the most favorable and eco-friendly for SMX transformation, as it resulted in a high rate of SMX dissipation from water without an increase in toxicity and subsequent formation of significant stable NERs in sediment. Our study comprehensively revealed the abiotic and biotic transformation processes of SMX under controlled redox conditions and demonstrated iron-reducing condition allowing optimal removal of SMX in constructed wetlands.


Asunto(s)
Sulfametoxazol , Humedales , Sulfametoxazol/química , Nitratos , Antibacterianos , Oxidación-Reducción , Hierro , Compuestos Orgánicos , Agua
8.
Int Immunopharmacol ; 129: 111646, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38325046

RESUMEN

Glaucoma, an insidious ophthalmic pathology, is typified by an aberrant surge in intraocular pressure (IOP) which culminates in the degeneration of retinal ganglion cells and optical neuropathy. The mitigation of IOP stands as the principal therapeutic strategy to forestall vision loss. The trabecular meshwork's (TM) integrity and functionality are pivotal in modulating aqueous humor egress. Despite their potential significance in glaucomatous pathophysiology, the implications of microRNAs (miRNAs) on TM functionality remain largely enigmatic. Transcriptomic sequencing was employed to delineate the miRNA expression paradigm within the limbal region of rodent glaucoma models, aiming to elucidate miRNA-mediated mechanisms within the glaucomatous milieu. Analytical scrutiny of the sequencing data disclosed 174 miRNAs with altered expression profiles, partitioned into 86 miRNAs with augmented expression and 88 with diminished expression. Notably, miRNAs such as hsa-miR-196b-5p were identified as having substantial expression discrepancies with concomitant statistical robustness, suggesting a potential contributory role in glaucomatous progression. Subsequent in vitro assays affirmed that miR-196b-5p augments the inflammatory cascade within immortalized human TM (iHTM) and glaucoma-induced human TM (GTM3) cells, concurrently attenuating cellular proliferation, motility, and cytoskeletal architecture. Additionally, miR-196b-5p implicates itself in the regulation of IOP and inflammatory processes in rodent models. At a mechanistic level, miR-196b-5p modulates its effects via the targeted repression of Nras (neuroblastoma RAS viral oncogene homolog). Collectively, these transcriptomic investigations furnish a comprehensive vista into the regulatory roles of miRNAs within the glaucomatous framework, and the identification of differentially expressed miRNAs alongside their targets could potentially illuminate novel molecular pathways implicated in glaucoma, thereby aiding in the development of innovative therapeutic avenues.


Asunto(s)
Glaucoma , MicroARNs , Humanos , Humor Acuoso/metabolismo , Línea Celular Tumoral , Glaucoma/genética , MicroARNs/metabolismo , Malla Trabecular
9.
Cytokine ; 175: 156483, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38159472

RESUMEN

PURPOSE: The purpose of this research study was to investigate the impact of schaftoside on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms. METHODS: In order to establish safe experimental concentrations of schaftoside in human corneal epithelial cells (HCECs), RAW264.7 cells, and mouse models, various techniques were employed including cytotoxicity assay (CCK-8) assay, cell scratch assay, and Draize test. The therapeutic effect of schaftoside was assessed using slit-lamp biomicroscopy, clinical scores, as well as determination of neutrophil infiltration through hematoxylin and eosin (HE) staining, immunofluorescence (IF) staining, and myeloperoxidase (MPO) assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), pro-inflammatory mediators interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 were determined using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and IF techniques. RESULTS: Schaftoside at a concentration of 160 µM displayed no harmful side effects on HCECs, RAW cells, and mouse corneas, rendering it suitable for further experiments. In a murine fungal keratitis model, schaftoside mitigated the severity of fungal keratitis by inhibiting neutrophil infiltration and reducing MPO activity. Both in vitro and in vivo experiments demonstrated that schaftoside treatment suppressed the upregulation of IL-1ß, TNF-α, and IL-6 expression, while also downregulating the expressions of TLR4 as well as MyD88 at both mRNA and protein levels. CONCLUSIONS: Schaftoside demonstrated a protective effect against A. fumigatus keratitis by reducing corneal damage through inhibition of neutrophil recruitment and downstream inflammatory cytokines. The anti-inflammatory properties of schaftoside in A. fumigatus keratitis may involve modulation of the TLR4/MyD88 pathway.


Asunto(s)
Aspergilosis , Glicósidos , Queratitis , Animales , Ratones , Humanos , Aspergillus fumigatus , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/metabolismo , Aspergilosis/tratamiento farmacológico , Interleucina-6/metabolismo , Queratitis/tratamiento farmacológico , Queratitis/metabolismo , Queratitis/microbiología , Inflamación/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Ratones Endogámicos C57BL
11.
Signal Transduct Target Ther ; 8(1): 311, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37607925

RESUMEN

As key organelles involved in cellular metabolism, mitochondria frequently undergo adaptive changes in morphology, components and functions in response to various environmental stresses and cellular demands. Previous studies of mitochondria research have gradually evolved, from focusing on morphological change analysis to systematic multiomics, thereby revealing the mitochondrial variation between cells or within the mitochondrial population within a single cell. The phenomenon of mitochondrial variation features is defined as mitochondrial heterogeneity. Moreover, mitochondrial heterogeneity has been reported to influence a variety of physiological processes, including tissue homeostasis, tissue repair, immunoregulation, and tumor progression. Here, we comprehensively review the mitochondrial heterogeneity in different tissues under pathological states, involving variant features of mitochondrial DNA, RNA, protein and lipid components. Then, the mechanisms that contribute to mitochondrial heterogeneity are also summarized, such as the mutation of the mitochondrial genome and the import of mitochondrial proteins that result in the heterogeneity of mitochondrial DNA and protein components. Additionally, multiple perspectives are investigated to better comprehend the mysteries of mitochondrial heterogeneity between cells. Finally, we summarize the prospective mitochondrial heterogeneity-targeting therapies in terms of alleviating mitochondrial oxidative damage, reducing mitochondrial carbon stress and enhancing mitochondrial biogenesis to relieve various pathological conditions. The possibility of recent technological advances in targeted mitochondrial gene editing is also discussed.


Asunto(s)
ADN Mitocondrial , Mitocondrias , Estudios Prospectivos , Mitocondrias/genética , ADN Mitocondrial/genética , Edición Génica , Proteínas Mitocondriales
12.
Sci Total Environ ; 896: 165242, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37394068

RESUMEN

Traditional health risk assessment of trace metal(loid)s (TMs) in agricultural soil exclusively considers direct soil-related exposure and may underestimate the health risks they pose. In this study, the health risks of TMs were evaluated using an integrated model that combined soil-related and plant-accumulating exposures. A detailed investigation of common TMs (Cr, Pb, Cd, As, and Hg) coupled with probability risk analysis based on a Monte Carlo simulation was conducted on Hainan Island. Our results showed that, except for As, the non-carcinogenic risk (HI) and carcinogenic risk (CR) of the TMs were all within the acceptable ranges (HI < 1.0, and CR < 1E-06) for direct soil-related exposure to bio-accessible fractions and indirect exposure via plant accumulation (CR substantially lower than the warning threshold 1E-04). We identified crop food ingestion as the essential pathway for TM exposure and As as the critical toxic element in terms of risk control. Moreover, we determined that RfDo and SFo are the most suitable parameters for assessing As health risk severity. Our study demonstrated that the proposed integrated model combining soil-related and plant-accumulating exposures can avoid major health risk assessment deviations. The results obtained and the integrated model proposed in this study can facilitate future multi-pathway exposure research and could be the basis for determining agricultural soil quality criteria in tropical areas.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Oligoelementos , Suelo , Metales Pesados/análisis , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , Medición de Riesgo , China , Carcinógenos/análisis
13.
Huan Jing Ke Xue ; 44(6): 3034-3042, 2023 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-37309922

RESUMEN

Rapid urbanization has increased the complexity of the urban heat environment system, which has negative impacts on the health of the urban ecological system and the human habitat. By combining theories and technologies such as geographic information systems, remote sensing, morphological spatial pattern analysis, and circuit theory with data from MODIS land surface temperature production, urban heat island patches in the Beijing-Tianjin-Hebei urban agglomeration were quantitatively identified in terms of their spatial and temporal distribution characteristics and their spatial and temporal transfer paths. This foundation revealed the geographical network structure of the urban heat environment as well as the spatial and temporal evolution process of critical corridors. According to the findings, urban heat island patches covered 16610 km2 in 2020, accounting for 7.68% of the study area. In the Beijing-Tianjin-Hebei urban agglomeration, both the area and the number of urban heat island patches considerably increased between 2005 and 2020, going from being dominated by isolated island types of urban heat island patches in 2005 to being dominated by core types in 2020. In particular, the non-urban heat island patches, core type, and edge type of urban heat island patches in 2005 were the major ancestors of the core type and edge type urban heat island patches in 2020. In the Beijing-Tianjin-Hebei urban agglomeration, there were more urban heat environment source sites, corridor length, densities, and present densities in 2020 than there were in 2005. The sensitive corridor was found to be the predominant type of urban heat island corridor in the Beijing-Tianjin-Hebei urban agglomeration in 2020. The number of sensitive corridors increased the highest in the period from 2005-2020. As the coefficient of urban heat environment corridors increased concurrently, it was apparent that the urban heat environment corridor had a propensity to grow continuously in the Beijing-Tianjin-Hebei urban agglomeration. The active adaptation and mitigation measures of the urban heat environment were proposed, and a spatial network model of the urban heat environment was finally provided. To adapt to, mitigate, and promote urban sustainable development risks, these research findings will serve as a paradigm for the identification of the urban heat environment spatial network actively and methodically.

14.
World J Clin Cases ; 11(12): 2796-2802, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37214565

RESUMEN

BACKGROUND: Inferior oblique anterior transposition (IOAT) has emerged as an effective surgery in the management of dissociated vertical deviation (DVD) combined with superior oblique palsy (SOP). Traditional IOAT usually provides satisfactory primary position alignment and simultaneously restricts the superior floating phenomenon. However, it also increases the risk of the anti-elevation syndrome and narrowing of the palpebral fissure in straight-ahead gaze, especially after the unilateral operation. CASE SUMMARY: We report the outcomes of the modified unilateral IOAT in two patients with unilateral DVD combined with SOP. The anterior-nasal fibers of the inferior oblique muscle were attached at 9 mm posterior to the corneal limbus along the temporal board of the inferior rectus muscle, the other fibers were attached a further 5 mm temporal to the anterior-nasal fibers. Postoperatively, both hypertropia and floating were improved, and no obvious complications occurred. CONCLUSION: In these cases, the modified unilateral IOAT was an effective and safe surgical method for treating DVD with SOP.

15.
Urolithiasis ; 51(1): 77, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37093335

RESUMEN

A retrospective study was performed on 200 patients who underwent miniaturized percutaneous nephrolithotomy (mini-PCNL) or retrograde intrarenal surgery (RIRS) for 10-20 mm sized lower pole renal calculi to investigate the relationship between computed tomography (CT) attenuation of calculi and surgical outcomes. CT was used to examine the location, size, and CT attenuation values of the calculi. Additionally, the operation time, hospital stay, hemoglobin (Hb) reduction, stone-free rate (SFR), and complication rate were also meticulously documented and subjected to comparative analysis. Complications were assessed using the Clavien-Dindo grading system. We observed no significant differences in hospitalization data and follow-up outcomes, except for a longer hospital stay and higher Hb drops in patients receiving mini-PCNL. Statistical analysis revealed an association between CT attenuation and operation time. Compared with mini-PCNL, RIRS could reduce bleeding, hospital stay, surgery time, and complications for 10-20 mm sized lower pole kidney stones with CT values < 1000 HU. RIRS resulted in longer operation time and lower stone-free rates despite shorter hospital stays and less bleeding than mini-PCNL for stones with CT values > 1000 HU. Therefore, selecting an appropriate surgical method based on CT attenuation might improve outcomes. For patients with stone attenuation values < 1000 HU, RIRS is the recommended option. When stone attenuation values > 1000 HU, the surgical method should be chosen based on the patient's individual situation.


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Cirujanos , Humanos , Nefrolitotomía Percutánea/métodos , Estudios Retrospectivos , Nefrostomía Percutánea/efectos adversos , Cálculos Renales/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
16.
FASEB J ; 37(4): e22873, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36929360

RESUMEN

Trabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM3 ) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real-time PCR analysis (qRT-PCR), western blotting, and CCK-8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/ß-catenin pathway activity was inferred from qRT-PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT-PCR and western blotting. SNHG11 was downregulated in GTM3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/ß-catenin signaling pathway, and activated Rho/ROCK. Wnt/ß-catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/ß-catenin signaling through Rho/ROCK by increasing GSK-3ß expression and ß-catenin phosphorylation at Ser33/37/Thr41 while decreasing ß-catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/ß-catenin signaling through Rho/ROCK via ß-catenin phosphorylation at Ser675 or GSK-3ß-mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, apoptosis, and autophagy. Through its effects on Wnt/ß-catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.


Asunto(s)
Glaucoma , Hipertensión Ocular , ARN Largo no Codificante , Humanos , Animales , Ratones , Vía de Señalización Wnt/fisiología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Malla Trabecular/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proliferación Celular/genética , Glaucoma/genética , Glaucoma/metabolismo , Hipertensión Ocular/metabolismo , Línea Celular Tumoral
17.
ISA Trans ; 132: 235-245, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35791971

RESUMEN

This paper proposes a new control strategy to deal with three different types of uncertainties for a class of time-varying delay nonlinear systems. Quite different from related celebrated works, the considered systems allow the existence of parameter uncertainties in the output function and nonlinearities, dynamic uncertainties of the unmeasurable state, and continuous external disturbances, which invokes the motivation of the paper. The objective is to construct a continuous output feedback controller by utilizing a new restructured integral function and the double-domination method. The novelty control design is the capability of tackling zero-dynamic and unknown output function simultaneously, thereby guaranteeing the state convergence of the closed-loop system. Finally, the proposed scheme is applied to a practical example and a numerical one simultaneously to demonstrate the effectiveness and the superiority.

18.
IEEE Trans Neural Netw Learn Syst ; 34(4): 1911-1920, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34464271

RESUMEN

This study concentrates on the tracking control problem for nonlinear systems subject to actuator saturation. To improve the performance of the controller, we propose a fixed-time tracking control scheme, in which the upper bound of the convergence time is independent of the initial conditions. In the control scheme, first, a smooth nonlinear function is employed to approximate the saturation function so that the controller can be designed under the framework of backstepping. Then, the effect of input saturation is compensated by introducing an auxiliary system. Furthermore, a fixed-time adaptive neural network control method is given with the help of fixed-time control theory, in which the dynamic order of controllers is reduced to a certain extent since there is only one updating law in the entire control design. Through rigorous theoretical analysis, it is concluded that the proposed control scheme can guarantee that: 1) the output tracking error can converge to a small neighborhood near the origin in a fixed time and 2) all signals in the closed-loop system are bounded. Finally, a numerical example and a practical example based on the single-link manipulator are provided to verify the effectiveness of the proposed method.

19.
IEEE Trans Cybern ; PP2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36446000

RESUMEN

This article is concerned with the global fast finite-time adaptive stabilization for a class of high-order uncertain nonlinear systems in the presence of serious nonlinearities and constraint communications. By renovating the technique of continuous feedback domination to the construction of a serial of integral functions with nested sign functions, this article first proposes a new event-triggered strategy consisting of a sharp triggered rule and a time-varying threshold. The strategy guarantees the existence of the solutions of the closed-loop systems and the fast finite-time convergence of original system states while reaching a compromise between the magnitude of the control and the trigger interval. Quite different from traditional methods, a simple logic is presented to avoid searching all the possible lower bounds of trigger intervals. An example of the maglev system and a numerical example are provided to demonstrate the effectiveness and superiority of the proposed strategy.

20.
Int J Ophthalmol ; 15(6): 857-867, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35814889

RESUMEN

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy. It may lead to postoperative nuclear cataract and increase the risk for glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous and encourages conducting vitreous interventions prudently if it is possible.

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