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1.
Front Cardiovasc Med ; 11: 1375750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988665

RESUMO

Purpose: The causal associations between inflammatory factors and atrial fibrillation (AF) remained unclear. We aimed to investigate whether genetically predicted inflammatory proteins are related to the risk of AF, and vice versa. Methods: A bidirectional two-sample Mendelian randomization study was performed. The genetic variation of 91 inflammatory proteins were derived from genome-wide association study (GWAS) data of European ancestry (n = 14,824). Summary statistics for AF were obtained from a published meta-analysis study (n = 1,030,836) and the FinnGen study (n = 261,395). Results: Genetically predicted fibroblast growth factor 5 (FGF5) was significantly positively associated with risk of AF [[odds ratio (OR): 1.07; 95% CI: 1.04-1.10; P < 0.01], and CD40l receptor was significantly negatively associated with risk of AF (OR: 0.95; 95% CI: 0.92-0.98; P = 0.02) in the meta-analysis study. In the FinnGen study, similar results were observed in FGF5 (OR: 1.11; 95% CI: 1.06-1.16; P < 0.01) and CD40l receptor (OR: 0.93; 95% CI: 0.89-0.97; P = 0.03) for AF. In the FinnGen study, TNF-beta was significantly positively associated with risk of AF (OR: 1.05; 95% CI: 1.02-1.09; P = 0.03) and leukemia inhibitory factor receptor was significantly negatively associated with risk of AF (OR: 0.86; 95% CI: 0.80-0.91; P = 0.001). The causal effect of AF on inflammatory proteins was not observed. Conclusion: Our study suggested that FGF5 and CD40l receptor have a potential causal association with AF, and targeting these factors may help in the treatment of AF.

2.
Front Cell Dev Biol ; 12: 1348894, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933333

RESUMO

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

3.
Chem Biol Drug Des ; 103(4): e14522, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38580458

RESUMO

Pyroptosis is a programmed cell death process that frequently occurs in many diseases, including hyperuricemic nephropathy (HN). In HN, a range of stimuli mediates inflammation, leading to the activation of inflammasomes and the production of gasdermin D (GSDMD). Baicalin (BA), a natural flavonoid renowned for its antioxidant and anti-inflammatory properties, was investigated for its role in HN in this study. Initially, HN-like inflammation and pyroptosis were induced in HK-2 cells with treatment of monosodium urate (MSU), followed by the BA treatment. The expression of pyroptosis-associated genes, Panx-1 and P2X7, at both mRNA and protein levels was assessed through real-time polymerase chain reaction (RT-qPCR) and Western blotting (WB) without or with BA treatment. The results showed that expression of Panx-1 and P2X7 at mRNA and protein levels was increased in MSU-treated HK-2 cells, which subsequently decreased upon the BA treatment. Further experiments showed that BA could combine NLRP3 inflammasome and GSDMD, destabilizing GSDMD protein. Moreover, BA protected the cell membrane from MSU-induced damage, as evidenced by Hoechst 33342 and PI double staining, lactate dehydrogenase (LDH) assays, and electron microscopy observations. These results suggest that BA is involved in the regulating Panx-1/P2X7 pathways and thus inhibits pyroptosis, highlighting its potential therapeutic effect for HN.


Assuntos
Piroptose , Ácido Úrico , Humanos , Simulação de Acoplamento Molecular , Células Epiteliais , Flavonoides/farmacologia , Inflamação , RNA Mensageiro/genética
4.
J Transl Med ; 22(1): 395, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685028

RESUMO

BACKGROUND: Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5'-C; antisense strand, 3'-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy. METHODS: IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5'-C; antisense strand, 3'-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-ß and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection. RESULTS: IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-ß and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors. CONCLUSIONS: This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5'-C; antisense strand, 3'-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field.


Assuntos
Apoptose , Glioma , RNA Interferente Pequeno , Humanos , Animais , Linhagem Celular Tumoral , Glioma/terapia , Glioma/patologia , Glioma/genética , RNA Interferente Pequeno/metabolismo , Camundongos Nus , Proteína DEAD-box 58/metabolismo , Proteína DEAD-box 58/genética , Proliferação de Células , Movimento Celular , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Espécies Reativas de Oxigênio/metabolismo , Invasividade Neoplásica , Sobrevivência Celular
5.
Int Immunopharmacol ; 132: 111998, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38593510

RESUMO

BACKGROUND: Given the intricate molecular complexities and heterogeneity inherent in T-cell immunotherapy of gastric cancer (GC), elucidative T-cell-related biomarkers were imperative needed for facilitating the prediction of GC patient prognosis and identify potential synergistic therapeutic targets. METHODS: We conducted COX regression analysis in TISIDB, TCGA-STAD, and GEO databases to identify 19 GC T-cell-mediated sensitivity tumor killing (TTK) genes (key GCTTKs). Based on key GCTTKs, we constructed two TTK patterns and analyzed their metabolic pathways, mutation features, clinical data distribution, immune cell infiltration, and prognosis. LASSO regression was performed to develop a T-cell-mediated GC Prognosis (TGCP) model. We validated the TGCP model in GC patients. TAP1 was further selected for investigation of its biological functions and molecular mechanisms. We assessed the potential of TAP1 as a promising therapeutic target for GC using Patient-derived organoids (PDOs)-derived xenografts (PDOXs) models of GC. RESULTS: The TTK patterns display notable disparities. The TGCP model showcases its proficiency in predicting immune response efficacy, effectively distinguishes immunotherapy difference GC patients. Our findings find further confirmation in PDOX models, affirming TAP1 can enhance immunotherapy facilitated by PDL1 inhibitors. Furthermore, Oxaliplatin, by promoting TAP1 expression, augments PDL1 expression, thereby enhancing the efficacy of immunotherapy. CONCLUSIONS: We constructed a TGCP model, which demonstrates satisfactory predictive accuracy. Out of 9 prognostic genes, TAP1 was validated as a synergistic target for Oxaliplatin and PDL1 inhibitors, offering a genetic-level explanation for the synergy observed in GC treatment involving Oxaliplatin in combination with PDL1 inhibitors.


Assuntos
Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Imunoterapia , Oxaliplatina , Neoplasias Gástricas , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/terapia , Neoplasias Gástricas/genética , Humanos , Animais , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Imunoterapia/métodos , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Camundongos , Linfócitos T/imunologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Sinergismo Farmacológico , Prognóstico
6.
Biochem Pharmacol ; 222: 116120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461905

RESUMO

The role of the Immunoglobulin Superfamily (IgSF) as adhesion molecules in orchestrating inflammation is pivotal, yet its specific involvement in gastric cancer (GC) remains unknown. We analyzed IgSF components and discerned conspicuously elevated VCAM1 expression in GC, correlating with a poor prognosis. Remarkably, VCAM1 enhances GC cell proliferation and migration by activating AKT-mTOR signaling. Moreover, lactate in the tumor microenvironment (TME) promotes dynamic lactylation of H3K18 (H3K18la), leading to transcriptional activation of VCAM1 in GC cells. Furthermore, VCAM1 actively mediates intercellular communication in the TME. AKT-mTOR-mediated CXCL1 expression is increased by VCAM1, facilitating the recruitment of human GC-derived mesenchymal stem cells (hGC-MSCs), thereby fostering immunesuppression and accelerating cancer progression. In summary, H3K18 lactylation upregulated VCAM1 transcription, which activated AKT-mTOR signaling, and promoted tumor cell proliferation, EMT Transition and tumor metastasis. VCAM1 upregulated CXCL1 expression by AKT-mTOR pathway, so as to facilitate hGC-MSCs and M2 macrophage recruitment and infiltration. These findings provide novel therapeutic targets for GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Movimento Celular , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Transição Epitelial-Mesenquimal , Microambiente Tumoral , Quimiocina CXCL1/metabolismo
7.
Talanta ; 272: 125745, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367401

RESUMO

Laser-Induced Breakdown Spectroscopy (LIBS) instruments are increasingly recognized as valuable tools for detecting trace metal elements due to their simplicity, rapid detection, and ability to perform simultaneous multi-element analysis. Traditional LIBS modeling often relies on empirical or machine learning-based feature band selection to establish quantitative models. In this study, we introduce a novel approach-simultaneous multi-element quantitative analysis based on the entire spectrum, which enhances model establishment efficiency and leverages the advantages of LIBS. By logarithmically processing the spectra and quantifying the cognitive uncertainty of the model, we achieved remarkable predictive performance (R2) for trace elements Mn, Mo, Cr, and Cu (0.9876, 0.9879, 0.9891, and 0.9841, respectively) in stainless steel. Our multi-element model shares features and parameters during the learning process, effectively mitigating the impact of matrix effects and self-absorption. Additionally, we introduce a cognitive error term to quantify the cognitive uncertainty of the model. The results suggest that our approach has significant potential in the quantitative analysis of trace elements, providing a reliable data processing method for efficient and accurate multi-task analysis in LIBS. This methodology holds promising applications in the field of LIBS quantitative analysis.

8.
Opt Express ; 31(17): 27633-27653, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710835

RESUMO

Material characterization using laser-induced breakdown spectroscopy (LIBS) often relies on extensive data for effective analysis. However, data acquisition can be challenging, and the high dimensionality of raw spectral data combined with a large-scale sample dataset can strain computational resources. In this study, we propose a small sample size stacking model based on femtosecond LIBS to achieve accurate qualitative analysis of aluminum alloys. The proposed three-layer stacking algorithm performs data reconstruction and feature extraction to enhance the analysis. In the first layer, random forest spectral feature selection and specific spectral line spreading are employed to reconstruct the data. The second layer utilizes three heterogeneous classifiers to extract features from the reconstructed spectra in different feature spaces, generating second-level reconstructed data. Finally, the third layer utilizes the reconstructed dataset for qualitative prediction. Results indicate that the Stacking algorithm outperforms traditional methods such as k-nearest neighbors (KNN), support vector machine (SVM), and random forest (RF), including those combined with principal component analysis (PCA). The Stacking algorithm achieves an impressive 100% recognition rate in classification, with Accuracy, precision, recall, and F1 scores reaching 1.0. Moreover, as the number of samples decreases, the gap between the recognition accuracy of the Stacking algorithm and traditional approaches widens. For instance, using only 15 spectra for training, the Stacking algorithm achieves a recognition accuracy of 96.47%, significantly surpassing the improved RF's accuracy of 71.76%. Notably, the model demonstrates strong robustness compared to traditional modeling approaches, and the qualitative prediction error remains consistently below 5%. These findings underscore the model's enhanced generalization ability and higher prediction accuracy in small sample machine learning. This research contributes significantly to improving the applicability of the LIBS technique for fast detection and analysis of small samples. It provides valuable insights into the development of effective methodologies for material characterization, paving the way for advancements in the field.

9.
J Vis Exp ; (197)2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37486122

RESUMO

Posterior capsule opacification (PCO) is a common postoperative complication of extracapsular cataract surgery, which is caused by the proliferation and migration of lens epithelial cells and can affect long-term visual outcomes significantly. The most effective treatment for PCO is neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy; however, this treatment is associated with posterior segment complication and can break the stability of capsular bag, affecting the position and function of trifocal or toric intraocular lenses (IOLs). Advances in surgical procedures, IOL design, and pharmacy have reduced the rate of PCO in recent years, concentrating on the inhibition of proliferative lens epithelial cells (LECs). This protocol aimed to clear LECs more thoroughly during phacoemulsification and IOL implantation. The first several steps, including clear corneal incision, continuous circular capsulorhexis, hydrodissection, hydrodelineation, and phacoemulsification, were completed as conventional procedures. After placing the IOL into the capsular bag, rotation of the IOL by at least 360° was performed using an irrigation/aspiration tip or a hook, with slight stress on the posterior capsule. Some residuals occurred in the originally transparent capsular bag after rotation of the IOLs. Then, these materials and the viscoelastic were cleared completely using an irrigation/aspiration system. A clear posterior capsule was observed after the surgery in patients undergoing this method. This method of rotating IOLs is a simple, effective, and safe way to prevent PCO by clearing residual LECs and can be carried out without extra tools or skills.


Assuntos
Opacificação da Cápsula , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Humanos , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/prevenção & controle , Opacificação da Cápsula/cirurgia , Implante de Lente Intraocular/efeitos adversos , Implante de Lente Intraocular/métodos , Cápsula do Cristalino/cirurgia , Desenho de Prótese , Lentes Intraoculares/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Catarata/complicações , Catarata/prevenção & controle
10.
BMC Ophthalmol ; 23(1): 239, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248492

RESUMO

BACKGROUND: Corneal ectatic diseases are a group of corneal disorder characterized by the steepening and thinning of the cornea. Older people are not a high-risk population for corneal ectatic diseases; due to the lack of typical preoperative topographic manifestations, there is a high possibility that corneal ectasia is undetected. CASE PRESENTATION: Two patients with subclinical corneal ectasia and senile cataracts presented with irregular astigmatism after steep-axis incision during cataract surgery. The two cases presented in this case report are rare because both patients experienced tremendous changes in astigmatism after cataract surgery. CONCLUSION: This case report may shed some light on astigmatism-correcting steep-axis incisions in cataract surgeries.


Assuntos
Astigmatismo , Extração de Catarata , Catarata , Doenças da Córnea , Facoemulsificação , Humanos , Idoso , Astigmatismo/diagnóstico , Astigmatismo/etiologia , Astigmatismo/cirurgia , Dilatação Patológica/etiologia , Facoemulsificação/efeitos adversos , Implante de Lente Intraocular/efeitos adversos , Extração de Catarata/efeitos adversos , Córnea/cirurgia , Catarata/complicações , Catarata/diagnóstico , Doenças da Córnea/diagnóstico , Doenças da Córnea/etiologia , Doenças da Córnea/cirurgia , Topografia da Córnea
11.
ACS Nano ; 17(12): 11466-11480, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37201179

RESUMO

Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. Fusobacterium nucleatum, a core pathogen of colorectal cancer (CRC), is an important cause of low therapeutic efficacy and metastasis. Thus, the modulation of intratumoral pathogens may provide a target for cancer therapy and metastasis inhibition. Herein, we propose an intratumoral F. nucleatum-modulating strategy for enhancing the therapeutic efficacy of CRC and inhibiting lung metastasis by designing an antibacterial nanoplatform (Au@BSA-CuPpIX), which produced reactive oxygen species (ROS) under ultrasound and exhibited strong antibacterial activity. Importantly, Au@BSA-CuPpIX reduced the levels of apoptosis-inhibiting proteins by inhibiting intratumoral F. nucleatum, thereby enhancing ROS-induced apoptosis. In vivo results demonstrated that Au@BSA-CuPpIX effectively eliminated F. nucleatum to enhance the therapeutic efficacy of sonodynamic therapy (SDT) for orthotopic CRC and inhibit lung metastasis. Notably, entrapped gold nanoparticles reduced the phototoxicity of metalloporphyrin accumulated in the skin during tumor treatment, preventing severe inflammation and damage to the skin. Therefore, this study proposes a strategy for the elimination of F. nucleatum in CRC to enhance the therapeutic effect of SDT, thus providing a promising paradigm for improving cancer treatment with fewer toxic side effects and promoting the clinical translational potential of SDT.


Assuntos
Neoplasias Colorretais , Nanopartículas Metálicas , Humanos , Fusobacterium nucleatum/fisiologia , Neoplasias Colorretais/tratamento farmacológico , Ouro/uso terapêutico , Espécies Reativas de Oxigênio , Nanopartículas Metálicas/uso terapêutico
12.
Gastric Cancer ; 26(4): 565-579, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37062785

RESUMO

BACKGROUND: Gastric cancer (GC) is a cancer of the gastrointestinal tract that is highly malignant and has poor prognosis. Circular RNAs are a class of nonclassical RNA molecules that have been determined to be involved in GC malignancy in various ways. However, the underlying function and mechanism of circTDRD3 in gastric cancer remain largely unknown. METHODS: We analyzed circTDRD3 expression in databases and verified the findings in GC cell lines and tissue specimens. A series of functional gene overexpression and knockdown assays in vivo and in vitro were carried out to investigate the role of circTDRD3 in proliferation and metastasis. Here, we revealed the role of the miR-891b/ITGA2 axis by analyzing bioinformatics datasets. Furthermore, we performed dual-luciferase, fluorescence in situ hybridization, RNA pull-down, and functional rescue experiments to examine the relationships between circTDRD3 and its interacting molecules. Western blot confirmed the positive regulatory role of circTDRD3 in the AKT signaling pathway. A promoting effect of ATF4 on circTDRD3 was determined through chromatin immunoprecipitation. RESULTS: CircTDRD3 was significantly overexpressed in GC tissues compared with adjacent benign tissue, and its expression level was positively correlated with tumor volume and lymph node metastasis. CircTDRD3 promoted GC cell proliferation and migration in vitro and in vivo. Mechanistically, circTDRD3 exerted a tumor-promoting effect by regulating the miR-891b/ITGA2 axis and AKT signaling pathway in a positive feedback manner mediated by the transcription factor ATF4. CONCLUSIONS: ATF4-mediated circTDRD3 overexpression modulates the proliferation and metastasis of GC cells through the miR-891b/ITGA2 axis in a positive feedback manner.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/patologia , Hibridização in Situ Fluorescente , Transdução de Sinais , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo
13.
Mater Today Bio ; 19: 100606, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37063247

RESUMO

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

14.
Nephrology (Carlton) ; 28(6): 315-327, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36974463

RESUMO

AIM: Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN. METHODS: HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells. RESULTS: Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells. CONCLUSION: BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.


Assuntos
Hiperuricemia , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ácido Úrico , Simulação de Acoplamento Molecular , Transdução de Sinais , Inflamação , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico
15.
Bioengineering (Basel) ; 10(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36671692

RESUMO

In early corneal examinations, the relationships between the morphological and biomechanical features of the cornea were unclear. Although consistent links have been demonstrated between the two in certain cases, these are not valid in many diseased states. An accurate assessment of the corneal biomechanical properties is essential for understanding the condition of the cornea. Studies on corneal biomechanics in vivo suggest that clinical problems such as refractive surgery and ectatic corneal disease are closely related to changes in biomechanical parameters. Current techniques are available to assess the mechanical characteristics of the cornea in vivo. Accordingly, various attempts have been expended to obtain the relevant mechanical parameters from different perspectives, using the air-puff method, ultrasound, optical techniques, and finite element analyses. However, a measurement technique that can comprehensively reflect the full mechanical characteristics of the cornea (gold standard) has not yet been developed. We review herein the in vivo measurement techniques used to assess corneal biomechanics, and discuss their advantages and limitations to provide a comprehensive introduction to the current state of technical development to support more accurate clinical decisions.

16.
Int Ophthalmol ; 43(3): 779-793, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36056289

RESUMO

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.


Assuntos
Síndromes do Olho Seco , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Lágrimas/química , Microscopia Confocal/métodos , Córnea/patologia , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/complicações
17.
J Clin Med ; 11(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36498585

RESUMO

Extranodal natural killer/T-cell lymphoma (ENKL) usually occurs in the nose or the nasopharynx, but extranasal and disseminated disease can occur. In this disease, orbital involvement is more commonly seen, but without nasal involvement is rare. A 61-year-old woman was referred with a one-month history of a remarkably enlarging salmon-colored mass arising in the right inner canthus, with redness and painlessness. The motility of the right eye was limited in the medial direction, with external deviation of the eyeball. A magnetic resonance imaging (MRI) scan of the orbits showed a mass of irregular shape located in the right inner canthus, without any sinus involvement. A histopathological examination concluded a diagnosis of primary orbital extranodal natural killer/T-cell lymphoma, nasal type. Her orbital mass significantly reduced to near disappeared after chemotherapy. From the first visit to the present, the survival duration of this patient was more than 1 year. This patient was still alive with a high quality of life and with no systemic metastasis. Extranodal natural killer/T-cell lymphoma, nasal type may primarily arise in the orbit without nasal involvement. Early discovery, early biopsy and diagnosis and early appropriate treatment can successfully control tumors and improve prognosis.

18.
BMC Ophthalmol ; 22(1): 421, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335303

RESUMO

BACKGROUND: To investigate the possible effect of implantable collamer lens (ICL) V4c on ocular biometric measurements by a new biometer Pentacam-AXL and partial coherence interferometry (PCI)-based IOLMaster 500 and intraocular lens power calculation using fourth-generation formula. METHODS: We retrospectively enrolled patients who underwent ICL (EVO-V4c, STAAR Surgical Co. Nidau, Switzerland) implantation surgery from September 2020 to November 2021. The Pentacam-AXL and IOLMaster 500 biometers were used to measure axial length (AL), anterior chamber depth (ACD), keratometry (K), white to white (WTW), and central corneal thickness (CCT) values before and at least 2 months after ICL V4c implantation. The IOL power was calculated using the Barrett Universal II formula. RESULTS: The study included 45 eyes in 28 patients. There was a significant increase in ALs (average 0.03 ± 0.07 mm, p = 0.01) and a significant decrease of ACDs (average 0.19 ± 0.17 mm, p < 0.001) based on Pentacam-AXL. Similar changes in ALs and ACDs were also found in IOLMaster 500. In addition, the difference in WTWs in the two devices and that of CCTs in Pentacam-AXL were statistically significant. However, the preoperative and postoperative K1 and K2 were separately comparable using either device. The IOL power calculated by the Barrett Universal II formula did not change significantly either by the software built in Pentacam-AXL or by manually putting the parameters of the IOLMaster 500 into the formula manually (p = 0.058, p = 0.675, respectively). CONCLUSIONS: Ocular parameters including ALs, ACDs, WTWs, and CCTs using a new Pentacam-AXL and standard PCI-based IOLMaster 500 changed significantly before and after the ICL V4c implantation, while IOL power prediction using the Barrett Universal II formula was little affected.


Assuntos
Lentes Intraoculares , Refração Ocular , Humanos , Estudos Retrospectivos , Biometria , Comprimento Axial do Olho
19.
BMC Ophthalmol ; 22(1): 392, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192712

RESUMO

BACKGROUND: During cataract phacoemulsification surgery, an Intrepid® balanced (IB) tip can achieve a larger amplitude, which may lead to higher energy efficiency than a Kelman (K) tip when paired with a torsional phaco platform. In this retrospective cohort study, we compared their energy efficiency and damage to the cornea under a new energy setting. METHODS: The medical records of 104 eyes of 79 patients were reviewed, with 47 eyes belonging to the IB group and 57 eyes belonging to the K group. All surgeries were performed on an Alcon Centurion® platform with gravity infiltration. Surgical parameters, visual outcome, central corneal thickness (CCT) changes, and endothelial cell density (ECD) loss rate were recorded and calculated. RESULTS: No significant differences in postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), total ultrasound time, estimated fluid aspirated, CCT changes, or ECD loss rate were observed between the two groups. We divided the included eyes into soft nucleus and hard nucleus subgroups and found lower cumulative dissipated energy (CDE, 8.15 ± 8.02 vs 14.82 ± 14.16, P = 0.023), cumulative torsional energy (CTE, 8.06 ± 7.87 vs 14.13 ± 13.02, P = 0.027), and cumulative longitudinal energy (CLE, 0.09 ± 0.17 vs 0.69 ± 1.37, P = 0.017) in the IB group than in the K group, implying less energy used and higher energy efficiency of the IB tip. CONCLUSION: Lower CLE in the IB group indicates fewer phaco tip obstructions and a significantly higher capability to conquer hard nuclei with IB tips with statistical significance. With an ultra-perfusion cannula, the balanced tip does not cause more corneal damage.


Assuntos
Facoemulsificação , Conservação de Recursos Energéticos , Endotélio Corneano , Humanos , Facoemulsificação/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Acuidade Visual
20.
Materials (Basel) ; 15(10)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35629490

RESUMO

Hot deformation behaviors of an antibacterial 50Cr15MoVCu tool steel were studied. The flow stress curves presented three typical characteristics: (i) a single peak dynamic recrystallization curve, (ii) a monotone incremental work-hardening curve, and (iii) the equilibrium dynamic recovery curve. The flow stress increased with the increase of the deformation rate at each deformation temperature and decreased with the increase of the deformation temperature at the same deformation rate. The thermal activation energy and material constants were Q of 461.6574 kJ/mol, A of 3.42 × 1017, and α of 0.00681 MPa−1, respectively. The high temperature constitutive equation was: Z=ε˙expQ/RT=3.42 × 1017sinh0.0068 × σ5.6807. Based on the processing maps and microstructure evolution, the best hot working process was a deformation temperature of 1050 °C and deformation rate of 0.001 s−1.

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