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1.
Cell Mol Life Sci ; 81(1): 305, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012348

RESUMEN

Lentiviral vectors have markedly enhanced gene therapy efficiency in treating congenital diseases, but their long-term safety remains controversial. Most gene therapies for congenital eye diseases need to be carried out at early ages, yet the assessment of related risks to ocular development posed by lentiviral vectors is challenging. Utilizing single-cell transcriptomic profiling on human retinal organoids, this study explored the impact of lentiviral vectors on the retinal development and found that lentiviral vectors can cause retinal precursor cells to shift toward photoreceptor fate through the up-regulation of key fate-determining genes such as PRDM1. Further investigation demonstrated that the intron and intergenic region of PRDM1 was bound by PHLDA1, which was also up-regulated by lentiviral vectors exposure. Importantly, knockdown of PHLDA1 successfully suppressed the lentivirus-induced differentiation bias of photoreceptor cells. The findings also suggest that while lentiviral vectors may disrupt the fate determination of retinal precursor cells, posing risks in early-stage retinal gene therapy, these risks could potentially be reduced by inhibiting the PHLDA1-PRDM1 axis.


Asunto(s)
Diferenciación Celular , Vectores Genéticos , Lentivirus , Retina , Células Madre , Factores de Transcripción , Humanos , Retina/metabolismo , Retina/citología , Lentivirus/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Vectores Genéticos/metabolismo , Vectores Genéticos/genética , Diferenciación Celular/genética , Células Madre/metabolismo , Células Madre/citología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Organoides/metabolismo , Organoides/citología , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Terapia Genética/métodos
2.
Mol Ther Nucleic Acids ; 35(2): 102200, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38831898

RESUMEN

Cancer-induced bone pain (CIBP) significantly impacts the quality of life and survival of patients with advanced cancer. Despite the established role of neurexins in synaptic structure and function, their involvement in sensory processing during injury has not been extensively studied. In this study using a rat model of CIBP, we observed increased neurexin 2 expression in spinal cord neurons. Knockdown of neurexin 2 in the spinal cord reversed CIBP-related behaviors, sensitization of spinal c-Fos neurons, and pain-related negative emotional behaviors. Additionally, increased acetylation of neurexin 2 mRNA was identified in the spinal dorsal horn of CIBP rats. Decreasing the expression of N-acetyltransferase 10 (NAT10) reduced neurexin 2 mRNA acetylation and neurexin 2 expression. In PC12 cells, we confirmed that neurexin 2 mRNA acetylation enhanced its stability, and neurexin 2 expression was regulated by NAT10. Finally, we discovered that the NAT10/ac4C-neurexin 2 axis modulated neuronal synaptogenesis. This study demonstrated that the NAT10/ac4C-mediated posttranscriptional modulation of neurexin 2 expression led to the remodeling of spinal synapses and the development of conscious hypersensitivity in CIBP rats. Therefore, targeting the epigenetic modification of neurexin 2 mRNA ac4C may offer a new therapeutic approach for the treatment of nociceptive hypersensitivity in CIBP.

3.
Exp Ther Med ; 27(5): 238, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38628661

RESUMEN

The aim of the present study was to investigate the possibility of reducing the damage to the donor site while preserving the functional recovery of the dorsum of the hand following burn injury. An attempt was made to analyze the effect of a phased surgery approach on inflammatory indicators. A two-phase treatment was administered on a total of 64 patients with deep second-degree burns on the dorsum of the hand who were admitted to Guangzhou Red Cross Hospital between January 2020 and March 2023. During phase I treatment, the wounds were covered with xenogeneic (porcine) skin, followed by the application of autologous thin intermediate thickness skin grafts for wound repair in phase II treatment 1 week later. The surgical results, complications, patient satisfaction and inflammatory response indicators were then analyzed. The mean wound healing time of these patients was found to be 21.94 days without complications. The mean survival rate was 98.66%, and the overall satisfaction score of the patients was high. Finally, the white blood cell, C-reactive protein and IL-6 levels of these patients were continuously decreased 2 days preoperatively and 2 days postoperatively in phase I, and 2 days preoperatively and 2 days postoperatively in phase II. In combination, the effect of phased autologous skin grafting in patients with severe second-degree burns on the dorsum of the hand was ideal, as it significantly reduced inflammatory response and was beneficial to the functional recovery of the hand. Therefore, phased autologous skin grafting is worthy of wider application.

4.
Biomimetics (Basel) ; 9(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38534836

RESUMEN

This research introduces an advanced robotic finger designed for future generalist robots, closely mimicking the natural structure of the human finger. The incorporation of rarely discussed anatomical structures, including tendon sheath, ligaments, and palmar plates, combined with the usage of anatomically proven 3D models of the finger, give rise to the highly accurate replication of human-like soft mechanical fingers. Benefiting from the accurate anatomy of muscle insertions with the utilization of Shape Memory Alloy (SMA) wires' muscle-like actuation properties, the bonding in-between the flexor tendons and extensor tendons allows for the realization of the central and lateral band of the finger anatomy. Evaluated using the computer vision method, the proposed robotic finger demonstrates a range of motion (ROM) equivalent to 113%, 87% and 88% of the human dynamic ROM for the DIP, PIP and MCP joints, respectively. The proposed finger possesses a soft nature when relaxed and becomes firm when activated, pioneering a new approach in biomimetic robot design and offering a unique contribution to the future of generalist humanoid robots.

5.
Int Immunopharmacol ; 130: 111519, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38442573

RESUMEN

This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis.


Asunto(s)
Lesión Pulmonar , MicroARNs , Proteínas del Tejido Nervioso , ARN Largo no Codificante , Sepsis , Animales , Ratones , Apoptosis/genética , Modelos Animales de Enfermedad , Lesión Pulmonar/microbiología , Lesión Pulmonar/terapia , MicroARNs/genética , ARN Largo no Codificante/administración & dosificación , ARN Largo no Codificante/genética , Sepsis/complicaciones , Sepsis/genética , Proteínas del Tejido Nervioso/genética , Células Madre Mesenquimatosas , Exosomas , Masculino , Ratones Endogámicos C57BL
6.
Front Microbiol ; 15: 1345800, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435685

RESUMEN

Food security is a crucial issue that has caused extensive concern, and the use of food flavors has become prevalent over time. we used the molecular biological techniques, preservative susceptibility testing, viable but non-culturable (VBNC) state induction testing, and a transcriptome analysis to examine the bacterial contamination of favored syrup and identify the causes and develop effective control measures. The results showed that Asaia lannensis WLS1-1 is a microorganism that can spoil food and is a member of the acetic acid bacteria families. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests showed that WLS1-1 was susceptible to potassium sorbate (PS), sodium benzoate (SB), and sodium sulffte (SS) at pH 4.0. It revealed a progressive increase in resistance to these preservatives at increasing pH values. WLS1-1 was resistant to PS, SB and SS with an MIC of 4.0, 2.0 and 0.5 g/L at pH 5.0, respectively. The MIC values exceed the maximum permissible concentrations that can be added. The induction test of the VBNC state demonstrated that WLS1-1 lost its ability to grow after 321 days of PS induction, 229 days of SB induction and 52 days of SS induction combined with low temperature at 4°C. Additionally, laser confocal microscopy and a propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) assay showed that WLS1-1 was still alive after VBNC formation. There were 7.192 ± 0.081 (PS), 5.416 ± 0.149 (SB) and 2.837 ± 0.134 (SS) log10(CFU/mL) of viable bacteria. An analysis of the transcriptome data suggests that Asaia lannensis can enter the VBNC state by regulating oxidative stress and decreasing protein synthesis and metabolic activity in response to low temperature and preservatives. The relative resistance of Asaia lannensis to preservatives and the induction of the VBNC state by preservatives are the primary factors that contribute to the contamination of favored syrup by this bacterium. To our knowledge, this study represents the first evidence of the ability of Asaia lannensis to enter the VBNC state and provides a theoretical foundation for the control of organisms with similar types of activity.

7.
J Photochem Photobiol B ; 252: 112862, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38330691

RESUMEN

Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are important natural source for many drugs. Ultraviolet B (UVB) radiation have been proved to have regulatory effect towards biosynthesis of TIAs, which were meaningful for boost of TIA production. To decipher more comprehensive molecular characteristics in C. roseus under UVB radiation, integrated analysis of the nuclear proteome together with the transcriptome data under UVB radiation were performed. Expression of genes related to transmembrane transporters gradually increased during the prolonged exposure to UVB radiation. Some of known TIA transporters were affected by UVB. Abundance of proteins associated with spliceosome and nucleocytoplasmic transport increased. Homologs belonging to ORCA and CrWRKY transcription factors family increased at both transcriptomic and proteomic levels. At the same time, the numbers of differential alternative splicing events between UVB-radiated and white-light-treated plants continuously increased. These results suggest that the nucleus participated in early response of C. roseus under UVB radiation, where alternative splicing events occurred and might regulate multiple pathways. Furthermore, integrative omics analysis indicates that expression of enzymes at the terminal stages of seco-iridoid pathway decreased with the prolonged radiation exposure, potentially inhibiting further rise of TIA synthesis under extended UVB exposure.


Asunto(s)
Catharanthus , Transcriptoma , Catharanthus/genética , Catharanthus/metabolismo , Proteómica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas
8.
ACS Biomater Sci Eng ; 10(2): 946-959, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38154081

RESUMEN

Extracellular vesicles (EVs) derived from human adipose mesenchymal stem cells (hADSCs) may exert a therapeutic benefit in alleviating sepsis-induced organ dysfunction by delivering cargos that include RNAs and proteins to target cells. The current study aims to explore the protective effect of miR-150-5p delivered by hADSC-EVs on sepsis-induced acute lung injury (ALI). We noted low expression of miR-150-5p in plasma and bronchoalveolar lavage fluid samples from patients with sepsis-induced ALI. The hADSC-EVs were isolated and subsequently cocultured with macrophages. It was established that hADSC-EVs transferred miR-150-5p to macrophages, where miR-150-5p targeted HMGA2 to inhibit its expression and, consequently, inactivated the MAPK pathway. This effect contributed to the promotion of M2 polarization of macrophages and the inhibition of proinflammatory cytokines. Further, mice were made septic by cecal ligation and puncture in vivo and treated with hADSC-EVs to elucidate the effect of hADSC-EVs on sepsis-induced ALI. The in vivo experimental results confirmed a suppressive role of hADSC-EVs in sepsis-induced ALI. Our findings suggest that hADSC-EV-mediated transfer of miR-150-5p may be a novel mechanism underlying the paracrine effects of hADSC-EVs on the M2 polarization of macrophages in sepsis-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , Sepsis , Humanos , Animales , Ratones , Sepsis/complicaciones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/terapia , MicroARNs/genética
9.
Nat Commun ; 14(1): 8265, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38092735

RESUMEN

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.

10.
Chem Catal ; 3(8)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37873035

RESUMEN

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans-dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis.

11.
Cell Biol Toxicol ; 39(6): 3219-3234, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37812360

RESUMEN

Investigation on a competitive endogenous RNA (ceRNA) network attracted lots of attention due its function in cancer regulation. Here, we probed into the possible molecular mechanism of circSSPO/microRNA-6820-5p (miR-6820-5p)/kallikrein-related peptidase 8 (KLK8)/PKD1 network in the esophageal squamous cell carcinoma (ESCC). Following whole-transcriptome sequencing and differential analysis in collected ESCC tissue samples, circRNA-miRNA-mRNA regulatory network affecting ESCC was investigated. After interaction measurement among circSSPO/miR-6820-5p/KLK8/PKD1, their regulatory roles in ESCC cell functions in vitro and xenograft tumor growth and lung metastasis in vivo were analyzed. The bioinformatics prediction and sequencing results screened that circSSPO, miR-6820-5p, KLK8, and PKD1 were associated with ESCC development. In ESCC, miR-6820-5p was expressed at very low levels, while circSSPO, KLK8, and PKD1 were highly expressed. In vitro cell experiments further proved that circSSPO competitively inhibited miR-6820-5p to induce ESCC cell malignant properties. Moreover, knockdown of KLK8 or PKD1 inhibited ESCC cell malignant properties. circSSPO also promoted the tumorigenic and metastasis of ESCC through the upregulation of KLK8 and PKD1 expression in vivo. We found that circSSPO was an oncogenic circRNA that was significantly abundant in ESCC tissues and circSSPO exhibited an oncogenic activity in ESCC by elevating expression of KLK8 and PKD1 through suppressing miR-6820-5p expression.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , ARN Circular , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Calicreínas/genética , Calicreínas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Regulación hacia Arriba/genética
12.
Int Immunopharmacol ; 124(Pt A): 110765, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37647681

RESUMEN

INTRODUCTION: This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). METHODS: The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. RESULTS: The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. CONCLUSION: miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation.


Asunto(s)
Cardiomiopatías , MicroARNs , Miocarditis , Animales , Ratones , Cardiomiopatías/genética , Proliferación Celular , Fibrosis , MicroARNs/genética , MicroARNs/metabolismo , Miocarditis/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteína p53 Supresora de Tumor/genética
13.
Res Sq ; 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37461542

RESUMEN

The gold π-acid activation under electrochemical condition is achieved for the first time. While EAO allowing easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications to come.

14.
Int Immunopharmacol ; 122: 110415, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37402340

RESUMEN

Monocyte-derived exosomes (Exos) have been implicated in inflammation-related autoimmune/inflammatory diseases via transferring bioactive cargoes to recipient cells. The purpose of this study was to investigate the possible effect of monocyte-derived Exos on the initiation and the development of acute lung injury (ALI) by delivering long non-coding RNA XIST. Key factors and regulatory mechanisms in ALI were predicted by bioinformatics methods. BALB/c mice were treated with lipopolysaccharide (LPS) to establish an ALI in vivo model and then injected with Exos isolated from monocytes transduced with sh-XIST to evaluate the effect of monocyte-derived exosomal XIST on ALI. HBE1 cells were co-cultured with Exos isolated from monocytes transduced with sh-XIST for further exploration of its effect. Luciferase reporter, RIP and RNA pull-down assays were performed to verify the interaction between miR-448-5p and XIST, miR-448-5p and HMGB2. miR-448-5p was significantly poorly expressed while XIST and HMGB2 were highly expressed in the LPS-induced mouse model of ALI. Monocyte-derived Exos transferred XIST into HBE1 cells where XIST competitively inhibited miR-448-5p and reduced the binding of miR-448-5p to HMGB2, thus upregulating the expression of HMGB2. Furthermore, in vivo data revealed that XIST delivered by monocyte-derived Exos downregulated miR-448-5p expression and up-regulated HMGB2 expression, ultimately contributing to ALI in mice. Overall, our results indicate that XIST delivered by monocyte-derived Exos aggravates ALI via regulating the miR-448-5p/HMGB2 signaling axis.


Asunto(s)
Lesión Pulmonar Aguda , MicroARNs , ARN Largo no Codificante , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Proteína HMGB2/genética , Monocitos/metabolismo , Lipopolisacáridos/efectos adversos , Factores de Transcripción , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/terapia , ARN Largo no Codificante/genética
15.
J Biochem Mol Toxicol ; 37(8): e23380, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37132394

RESUMEN

Chemoresistance remains a major obstacle to the treatment of esophageal cancer (EC). Exosome-mediated transfer of long noncoding RNAs (lncRNAs) has recently been unveiled to correlate with the regulation of drug resistance in EC. This study aimed to investigate the physiological mechanisms by which exosome-encapsulated lncRNA myocardial infarction-associated transcript (MIAT) derived from tumor cells might mediate the paclitaxel (PTX) resistance of EC cells. First, MIAT was experimentally determined to be upregulated in PTX nonresponders and PTX-resistant EC cells. Silencing of MIAT in PTX-resistant EC cells decreased cell viability and enhanced apoptosis, corresponding to a reduced half-maximal inhibitory concentration (IC50 ) value. Next, exosomes were isolated from EC109 and EC109/T cells, and EC109 cells were cocultured with EC109/T-cell-derived exosomes. Accordingly, MIAT was revealed to be transmitted through exosomes from EC109/T cells to EC109 cells. Tumor-derived exosomes carrying MIAT increased the IC50 value of PTX and suppressed apoptosis in EC109 cells to promote PTX resistance. Furthermore, MIAT promoted the enrichment of TATA-box binding protein-associated Factor 1 (TAF1) in the promoter region of sterol regulatory element binding transcription factor 1 (SREBF1), as shown by a chromatin immunoprecipitation assay. This might be the mechanism by which MIAT could promote PTX resistance. Finally, in vivo experiments further confirmed that the knockdown of MIAT attenuated the resistance of EC cells to PTX. Collectively, these results indicate that tumor-derived exosome-loaded MIAT activates the TAF1/SREBF1 axis to induce PTX resistance in EC cells, providing a potential therapeutic target for overcoming PTX resistance in EC.


Asunto(s)
Neoplasias Esofágicas , Exosomas , MicroARNs , Infarto del Miocardio , ARN Largo no Codificante , Humanos , Paclitaxel/farmacología , Exosomas/metabolismo , Línea Celular Tumoral , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , ARN Largo no Codificante/genética , MicroARNs/genética , Proliferación Celular , Proteína 1 de Unión a los Elementos Reguladores de Esteroles
16.
Int J Biol Macromol ; 240: 124353, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37059281

RESUMEN

Theaflavins (TFs) are important quality compounds in black tea with a variety of biological activities. However, direct extraction of TFs from black tea is inefficient and costly. Therefore, we cloned two PPO isozymes from Huangjinya tea, termed HjyPPO1 and HjyPPO3. Both isozymes oxidized corresponding catechin substrates for the formation of four TFs (TF1, TF2A, TF2B, TF3), and the optimal catechol-type catechin to pyrogallol-type catechin oxidation rate of both isozymes was 1:2. In particular, the oxidation efficiency of HjyPPO3 was higher than that of HjyPPO1. The optimum pH and temperature of HjyPPO1 were 6.0 and 35 °C, respectively, while those of HjyPPO3 were 5.5 and 30 °C, respectively. Molecular docking simulation indicated that the unique residue of HjyPPO3 at Phe260 was more positive and formed a π-π stacked structure with His108 to stabilize the active region. In addition, the active catalytic cavity of HjyPPO3 was more conducive for substrate binding by extensive hydrogen bonding.


Asunto(s)
Camellia sinensis , Catequina , Camellia sinensis/química , Catequina/química , Catecol Oxidasa/metabolismo , Isoenzimas , Simulación del Acoplamiento Molecular , Antioxidantes , Té/genética , Té/química , Clonación Molecular
17.
Sensors (Basel) ; 23(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36772677

RESUMEN

Intelligent operation and maintenance technology for vessels can ensure the safety of the entire system, especially for the development of intelligent and unmanned marine technology. The material properties of metal abrasive particles in oil could demonstrate the wear areas of the marine mechanical system because different components consist of different materials. However, most sensors can only roughly separate metallic contaminants into ferromagnetic and non-ferromagnetic particles but cannot differentiate them in greater detail. A micro-three-coil sensor is designed in this paper; the device applies different excitation signals to two excitation coils to differentiate materials, based on the different effects of different material particles in the asymmetric magnetic field. Therefore, a particle's material can be judged by the shape of the induction electromotive force output signal from the induction coil, while the particle size can be judged by the amplitude of the signal. Experimental results show that the material differentiation of four different types of particles can be achieved, namely, of aluminum, iron, 304 stainless steel, and carbon steel. This newly designed sensor provides a new research prospect for the realization of an inductive detection method to distinguish non-ferrous metals and a reference for the subsequent detection of metal contaminants in oil and other liquids.

18.
J Emerg Med ; 64(2): 200-207, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36710091

RESUMEN

BACKGROUND: Patients presenting to the emergency department with paralysis can have a wide differential diagnosis. Thyrotoxic periodic paralysis (TPP) is a rare disorder causing transient flaccid paralysis in the setting of thyrotoxicosis and hypokalemia. It has been reported in Asian male populations predominantly, and the diagnosis is rarely considered in non-Asian populations. Recent research has identified cases in patients with diverse ethnic backgrounds, although epidemiologic data from the United States are very limited. OBJECTIVE: Our aim was to report our experience with TPP at a tertiary care center in the United States. METHODS: A retrospective chart review was conducted between January 2006 and February 2022 to identify cases of TPP and determine their demographic and clinical characteristics. Prevalence of TPP was estimated using the institutional hyperthyroidism registry. RESULTS: Thirty-three patients with TPP were identified. All of the patients were male; median age was 28 years, and 85% were Hispanic. All patients had hypokalemia at presentation and 23% had rebound hyperkalemia after treatment. Prevalence of TPP in our population of patients with hyperthyroidism was approximately 0.5%. CONCLUSIONS: Young Hispanic men presenting with paralysis should be evaluated for TPP, as the prevalence in this population may be higher than estimated previously. Management of TPP involves treatment of underlying hyperthyroidism and cautious potassium repletion, with an initial dose of no more than 60 mEq/L of potassium chloride to avoid rebound hyperkalemia.


Asunto(s)
Hiperpotasemia , Hipertiroidismo , Hipopotasemia , Tirotoxicosis , Adulto , Humanos , Masculino , Hispánicos o Latinos , Hiperpotasemia/complicaciones , Hipertiroidismo/complicaciones , Hipopotasemia/etiología , Parálisis/diagnóstico , Estudios Retrospectivos , Tirotoxicosis/diagnóstico
19.
Sensors (Basel) ; 24(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38202916

RESUMEN

Magnetic plug-type abrasive particle sensors have a wide range of applications in oil detection, but there is little literature on the effect of abrasive particle position on detection accuracy. In this paper, an alternating current (AC) bridge-type abrasive particle detection sensor is designed, in which the sensing module utilizes permanent magnets to attract iron particles, and the induction coil is specially designed to detect the magnetic field fluctuation caused by iron particles. A corresponding model was also designed to evaluate the sensor's sensitivity at different locations. In this paper, the magnetic field distribution of the sensor was first analyzed using finite element analysis software to obtain the magnetic field strength at different positions. Then, the response sensitivity of the sensor to particles and the effect of different positions on the detection results are explored through experiments. The simulation and the experimental results show substantial signal difference signal at different sensor positions. The method outlined in this article can determine the optimal sensing range for subsequent magnetic plug-type abrasive particle detection sensors and subsequently improve their reliability.

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