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Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell-cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed. By convection-enhanced delivery, membrane-disrupted amphiphilic polymer micelles (poly(methoxypoly(ethylene glycol)-benzoic imine-octadecane, mPEG-b-C18) with CuS nanoflakes enhances tumor permeability and resides in deep brain tumors. Under low-power NIR II irradiation (0.8 W/cm2), the intense heat generated by well-distributed CuS nanoflakes actuates the thermolytic efficacy, facilitating cell apoptosis and the subsequent antigen release. Then, the positively charged polymer after hydrolysis of the benzoic-imine bond serves as an antigen depot, detaining autologous tumor-associated antigens and presenting them to dendritic cells, ensuring sustained immune stimulation. This self-cascading penetrative immunotherapy amplifies the immune response to postoperative brain tumors but also enhances survival outcomes through effective brain immunotherapy.
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Neoplasias Encefálicas , Membrana Celular , Células Dendríticas , Inmunoterapia , Rayos Infrarrojos , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Animales , Ratones , Humanos , Membrana Celular/química , Línea Celular Tumoral , Micelas , Nanopartículas/química , Terapia Fototérmica , Polietilenglicoles/química , Glioblastoma/terapia , Glioblastoma/inmunología , Glioblastoma/patología , Apoptosis/efectos de los fármacosRESUMEN
BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) accounts for up to 20% of all strokes and results in 40% mortality at 30 days. Although conservative medical management is still the standard treatment for ICH patients with small hematoma, patients with residual hematoma ≤15 mL after surgery are associated with better functional outcomes and survival rates. This study reported our clinical experience with using Robotic Stereotactic Assistance (ROSA) as a safe and effective approach for stereotactic ICH aspiration and intra-clot catheter placement. METHODS: A retrospective analysis was conducted of patients with spontaneous ICH who underwent ROSA-guided ICH aspiration surgery. ROSA-guided ICH surgical techniques, an aspiration and intra-clot catheter placement protocol, and a specific operative workflow (pre-operative protocol, intraoperative procedure and postoperative management) were employed to aspirate ICH using the ROSA One Brain, and appropriate follow-up care was provided. RESULTS: From September 14, 2021 to May 4, 2022, a total of 7 patients were included in the study. Based on our workflow design, ROSA-guided stereotactic ICH aspiration effectively aspirated more than 50% of hematoma volume (or more than 30 mL for massive hematomas), thereby reducing the residual hematoma to less than 15 mL. The mean operative time of entire surgical procedure was 1.3 ± 0.3 h, with very little perioperative blood loss and no perioperative complications. No patients required catheter replacement and all patients' functional status improved. CONCLUSIONS: Within our clinical practice ROSA-guided ICH aspiration, using our established protocol and workflow, was safe and effective for reducing hematoma volume, with positive functional outcomes.
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Microbially induced carbonate precipitation (MICP), as an eco-friendly and promising technology that can transform free metal ions into stable precipitation, has been extensively used in remediation of heavy metal contamination. However, its depressed efficiency of heavy metal elimination remains in question due to the inhibition effect of heavy metal toxicity on bacterial activity. In this work, an efficient, low-cost manganese (Mn) elimination strategy by coupling MICP with chitosan biopolymer as an additive with reduced treatment time was suggested, optimized, and implemented. The influences of chitosan at different concentrations (0.01, 0.05, 0.10, 0.15 and 0.30 %, w/v) on bacterial growth, enzyme activity, Mn removal efficiency and microstructure properties of the resulting precipitation were investigated. Results showed that Mn content was reduced by 94.5 % within 12â¯h with 0.15 % chitosan addition through adsorption and biomineralization as MnCO3 (at an initial Mn concentration of 3â¯mM), demonstrating a two-thirds decrease in remediation time compared to the chitosan-absent system, whereas maximum urease activity increased by â¼50 %. Microstructure analyses indicated that the mineralized precipitates were spherical-shaped MnCO3, and a smaller size and more uniform distribution of MnCO3 is obtained by the regulation of abundant amino and hydroxyl groups in chitosan. These results demonstrate that chitosan accelerates nucleation and tunes the growth of MnCO3 by providing nucleation sites for mineral formation and alleviating the toxicity of metal ions, which has the potential to upgrade MICP process in a sustainable and effective manner. This work provides a reference for further understanding of the biomineralization regulation mechanism, and gives a new perspective into the application of biopolymer-intensified strategies of MICP technology in heavy metal contamination.
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Carbonatos , Quitosano , Manganeso , Quitosano/química , Manganeso/química , Manganeso/toxicidad , Carbonatos/química , Adsorción , Biopolímeros/química , Precipitación Química , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/química , Ureasa , Restauración y Remediación Ambiental/métodos , Biomineralización/efectos de los fármacos , Biodegradación AmbientalRESUMEN
Endometriosis is a benign gynecological disease that shares some common features of malignancy. Autophagy plays vital roles in endometriosis and influences endometrial cell metastasis, and hypoxia was identified as the initiator of this pathological process through hypoxia inducible factor 1 alpha (HIF-1α). A newly discovered circular RNA FOXO3 (circFOXO3) is critical in cell autophagy, migration, and invasion of various diseases and is reported to be related to hypoxia, although its role in endometriosis remains to be elucidated up to now. In this study, a lower circFOXO3 expression in ectopic endometrium was investigated. Furthermore, we verified that circFOXO3 could regulate autophagy by downregulating the level of p53 protein to mediate the migration and invasion of human endometrial stromal cells (T HESCs). Additionally, the effects of HIF-1α on circFOXO3 and autophagy were examined in T HESCs. Notably, overexpression of HIF-1α could induce autophagy and inhibit circFOXO3 expression, whereas overexpressing of circFOXO3 under hypoxia significantly inhibited hypoxia-induced autophagy. Mechanistically, the direct combination between HIF-1α and HIF-1α-binding site on adenosine deaminase 1 acting on RNA (ADAR1) promoter increased the level of ADAR1 protein, which bind directly with circFOXO3 pre-mRNA to block the cyclization of circFOXO3. All these results support that hypoxia-mediated ADAR1 elevation inhibited the expression of circFOXO3, and then autophagy was induced upon loss of circFOXO3 via inhibition of p53 degradation, participating in the development of endometriosis.
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Endometriosis , Femenino , Humanos , Endometriosis/genética , Proteína p53 Supresora de Tumor , ARN , ARN Circular/genética , Autofagia , HipoxiaRESUMEN
BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.
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Ventriculitis Cerebral , Clorhexidina , Drenaje , Humanos , Ventriculitis Cerebral/etiología , Ventriculitis Cerebral/prevención & control , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Factores de Riesgo , Anciano , Adulto , Taiwán , Clorhexidina/análogos & derivados , Clorhexidina/uso terapéutico , Hemorragia Subaracnoidea , Paquetes de Atención al Paciente , Alcoholismo/complicacionesRESUMEN
N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.
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Endometriosis , ARN Largo no Codificante , Femenino , Humanos , Animales , ARN Largo no Codificante/genética , Transcriptoma , Endometriosis/genética , Adenosina , Metilación , MamíferosRESUMEN
PURPOSE: This study investigated the protective effect of probucol on Müller cells exposed to high glucose conditions and examined potential mechanisms of action. METHODS: Primary human retinal Müller cells were incubated with high glucose (HG, 35 mM) in the present or absence of different concentrations of probucol for 24 h. Cell viability was determined using the CCK-8 method. Mitochondrial membrane potential (MMP) was measured using JC-1 staining and cell cycle by flow cytometry. The expression of nuclear factor E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit, and p62 was quantified using quantitative polymerase chain reaction and western blot. RESULTS: We found that HG inhibited cell proliferation, arrested cell cycle, and increased MMP in human Müller cells. Probucol activated the Nrf2/p62 pathway and upregulated the anti-apoptotic protein, Bcl2, and attenuated HG-mediated damage in Müller cells. CONCLUSIONS: Our results suggest that probucol may protect Müller cells from HG-induced damage through enhancing the Nrf2/p62 signaling pathway.
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Células Ependimogliales , Probucol , Transducción de Señal , Humanos , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Factor 2 Relacionado con NF-E2 , Probucol/farmacologíaRESUMEN
We aim to understand the link between systemic and intraocular levels of inflammatory mediators in treatment-naïve retinal vein occlusion (RVO) patients, and the relationship between inflammatory mediators and retinal pathologies. Twenty inflammatory mediators were measured in this study, including IL-17E, Flt-3 L, IL-3, IL-8, IL-33, MIP-3ß, MIP-1α, GRO ß, PD-L1, CD40L, IFN-ß, G-CSF, Granzyme B, TRAIL, EGF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF, and FGFß. RVO patients had significantly higher levels of Flt-3 L, IL-8, MIP-3ß, GROß, and VEGF, but lower levels of EGF in the aqueous humor than cataract controls. The levels of Flt-3 L, IL-3, IL-33, MIP-1α, PD-L1, CD40 L, G-CSF, TRAIL, PDGF-AB/BB, TGF-α, and VEGF were significantly higher in CRVO than in BRVO. KEGG pathway enrichment revealed that these mediators affected the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways. Protein-Protein Interaction (PPI) analysis showed that VEGF is the upstream cytokine that influences IL-8, G-CSF, and IL-33 in RVO. In the plasma, the level of GROß was lower in RVO than in controls and no alterations were observed in other mediators. Retinal thickness [including central retinal thickness (CRT) and inner limiting membrane to inner plexiform layer (ILM-IPL)] positively correlated with the intraocular levels of Flt-3 L, IL-33, GROß, PD-L1, G-CSF, and TGF-α. The size of the foveal avascular zone positively correlated with systemic factors, including the plasma levels of IL-17E, IL-33, INF-ß, GROß, Granzyme B, and FGFß and circulating high/low-density lipids and total cholesterols. Our results suggest that intraocular inflammation in RVO is driven primarily by local factors but not circulating immune mediators. Intraocular inflammation may promote macular oedema through the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways in RVO. Systemic factors, including cytokines and lipid levels may be involved in retinal microvascular remodeling.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with complex pathophysiological mechanism. It is reported that even a modest weight loss of 5-10% substantially may improve the reproductive and metabolic profile. This study aims to assess the efficacy of the low dose of liraglutide (0.6 mg QD) combined with metformin (0.85 mg BID) in weight loss in Chinese Han women with PCOS. METHODS: We included clinical data of 102 obese/overweight (≥18 years, body mass index ≥28 kg/m2 or ≥24 kg/m2) women who were diagnosed with PCOS from October 2016 to March 2018 in Wuhan Union Hospital initially. They were treated with dinae-35, low dose of liraglutide (0.6 mg QD) and metformin (0.85 mg BID) for 12 weeks. The demographic and clinical data were retrieved retrospectively, and weight loss was the main outcome measure. Student's paired t-test and Wilcoxon rank sum test were used to compare the differences before and after therapy, p < 0.05 was considered statistically significant. RESULTS: Participants(n = 102)had lost a mean of 7.20 ± 3.42 kg of body weight (95%CI: 6.55-7.86, p < 0.001), and the mean reduction of BMI was 2.87 ± 1.36 kg/m2 (95%CI: 0.02-0.27, p < 0.001). A total of 88.24% of participants lost more than 5% of their body weight. CONCLUSION: The combination of low dose of liraglutide and metformin was associated with significant reduction of body weight in Chinese Han women with PCOS. Additionally, a larger randomized double-blind multicenter controlled clinical trial is needed to confirm that. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn as ChiCTR1900024384.
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Metformina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Peso Corporal , Pueblos del Este de Asia , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Estudios Retrospectivos , Pérdida de Peso , AdultoRESUMEN
Endometriosis is a chronic inflammatory disease distinguished by ectopic endometrium and fibrosis. NLRP3 inflammasome and pyroptosis are present in endometriosis. Aberrant increase of Long noncoding (Lnc)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a vital role in endometriosis. However, the relationship between lnc-MALAT1, pyroptosis, and fibrosis is not completely known. In the present study, we found that the pyroptosis levels in ectopic endometrium of patients with endometriosis were significantly increased, consistent with fibrosis levels. Lipopolysaccharide (LPS) + ATP could induce pyroptosis of primary endometrial stromal cells (ESCs), thereby releasing interleukin (IL)-1ß and stimulating transforming growth factor (TGF)-ß1-mediated fibrosis. NLRP3 inhibitor MCC950 had the same effect as TGF-ß1 inhibitor SB-431542 in suppressing the fibrosis-inducing effect of LPS + ATP in vivo and in vitro. The abnormal increase of lnc-MALAT1 in ectopic endometrium was connected with NLRP3-mediated pyroptosis and fibrosis. Leveraging bioinformatic prediction and luciferase assays combined with western blotting and quantitative reverse transcriptase-polymerase chain reaction, we validated that lnc-MALAT1 sponges miR-141-3p to promote NLRP3 expression. Silencing lnc-MALAT1 in HESCs ameliorated NLRP3-mediated pyroptosis and IL-1ß release, thereby relieving TGF-ß1-mediated fibrosis. Consequently, our findings suggest that lnc-MALAT1 is critical for NLRP3-induced pyroptosis and fibrosis in endometriosis through sponging miR-141-3p, which may indicate a new therapeutic target of endometriosis treatment.
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Endometriosis , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Endometriosis/genética , Lipopolisacáridos/farmacología , Fibrosis , Adenosina TrifosfatoRESUMEN
Glioblastoma multiforme (GBM) is a highly heterogeneous disease with a mesenchymal subtype tending to exhibit more aggressive and multitherapy-resistant features. Glioblastoma stem-cells derived from mesenchymal cells are reliant on iron supply, accumulated with high reactive oxygen species (ROS), and susceptible to ferroptosis. Temozolomide (TMZ) treatment is the mainstay drug for GBM despite the rapid development of resistance in mesenchymal GBM. The main interconnection between mesenchymal features, TMZ resistance, and ferroptosis are poorly understood. Herein, we demonstrated that a subunit of NADPH oxidase, CYBB, orchestrated mesenchymal shift and promoted TMZ resistance by modulating the anti-ferroptosis circuitry Nrf2/SOD2 axis. Public transcriptomic data re-analysis found that CYBB and SOD2 were highly upregulated in the mesenchymal subtype of GBM. Accordingly, our GBM cohort confirmed a high expression of CYBB in the GBM tumor and was associated with mesenchymal features and poor clinical outcome. An in vitro study demonstrated that TMZ-resistant GBM cells displayed mesenchymal and stemness features while remaining resilient to erastin-mediated ferroptosis by activating the CYBB/Nrf2/SOD2 axis. The CYBB maintained a high ROS state to sustain the mesenchymal phenotype, TMZ resistance, and reduced erastin sensitivity. Mechanistically, CYBB interacted with Nrf2 and consequently regulated SOD2 transcription. Compensatory antioxidant SOD2 essentially protected against the deleterious effect of high ROS while attenuating ferroptosis in TMZ-resistant cells. An animal study highlighted the protective role of SOD2 to mitigate erastin-triggered ferroptosis and tolerate oxidative stress burden in mice harboring TMZ-resistant GBM cell xenografts. Therefore, CYBB captured ferroptosis resilience in mesenchymal GBM. The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance.
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Neoplasias Encefálicas , Glioblastoma , Animales , Humanos , Ratones , Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , NADPH Oxidasa 2 , Factor 2 Relacionado con NF-E2/genética , Especies Reactivas de Oxígeno/metabolismo , Temozolomida/farmacología , Temozolomida/uso terapéuticoRESUMEN
With the development of economy, heavy metal (HM) contamination has become an issue of global concern, seriously threating animal and human health. Looking for appropriate methods that decrease their bioavailability in the environment is crucial. Microbially induced carbonate precipitation (MICP) has been proposed as a promising bioremediation method to immobilize contaminating metals in a sustainable, eco-friendly, and energy saving manner. However, its performance is always affected by many factors in practical application, both intrinsic and external. This paper mainly introduced ureolytic bacteria-induced carbonate precipitation and its implements in HM bioremediation. The mechanism of HM immobilization and in-situ application strategies (that is, biostimulation and bioaugmentation) of MICP are briefly discussed. The bacterial strains, culture media, as well as HMs characteristics, pH and temperature, etc. are all critical factors that control the success of MICP in HM bioremediation. The survivability and tolerance of ureolytic bacteria under harsh conditions, especially in HM contaminated areas, have been a bottleneck for an effective application of MICP in bioremediation. The effective strategies for enhancing tolerance of bacteria to HMs and improving the MICP performance were categorized to provide an in-depth overview of various biotechnological approaches. Finally, the technical barriers and future outlook are discussed. This review may provide insights into controlling MICP treatment technique for further field applications, in order to enable better control and performance in the complex and ever-changing environmental systems.
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Autophagy is an evolutionarily conserved cellular degradation and recycling process. It is important for maintaining vital cellular function and metabolism. Abnormal autophagy activity can cause the development of various diseases. N6-methyladenosine (m6A) methylation is the most prevalent and abundant internal modification in eukaryotes, affecting almost all aspects of RNA metabolism. The process of m6A modification is dynamic and adjustable. Its regulation depends on the regulation of m6A methyltransferases, m6A demethylases, and m6A binding proteins. m6A methylation and autophagy are two crucial and independent cellular events. Recent studies have shown that m6A modification mediates the transcriptional and post-transcriptional regulation of autophagy-related genes, affecting autophagy regulatory networks in multiple diseases. However, the regulatory effects of m6A regulators on autophagy in human diseases are not adequately acknowledged. In the present review, we summarized the latest knowledge of m6A modification in autophagy and elucidated the molecular regulatory mechanisms underlying m6A modification in autophagy regulatory networks. Moreover, we discuss the potentiality of m6A regulators serving as promising predictive biomarkers for human disease diagnosis and targets for therapy. This review will increase our understanding of the relationship between m6A methylation and autophagy, and provide novel insights to specifically target m6A modification in autophagy-associated therapeutic strategies.
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Regulación de la Expresión Génica , Metiltransferasas , Humanos , Metilación , Metiltransferasas/genética , Metiltransferasas/metabolismo , Autofagia/genéticaRESUMEN
Manganese (Mn), as a cofactor of multiple enzymes, exhibits great significance to the human body, plants and animals. It is also a critical raw material and alloying element. However, extensive employment for industrial purposes leads to its excessive emission into the environment and turns into a significant threat to the ecosystem and public health. This review firstly introduces the essentiality, toxicity and regulation of Mn. Several traditional physicochemical methods and their problems are briefly discussed as well. Biological remediation, especially microorganism-mediated strategies, is a potential alternative for remediating Mn-polluted environments in a cost-efficient and eco-friendly manner. Among them, microbially induced carbonate precipitation (MICP), biosorption, bioaccumulation, bio-oxidation are discussed in detail, including their mechanisms, pivotal influencing factors along with strengths and limitations. In order to promote bioremediation efficiency, the combination of different techniques is preferable, and their research progress is also summarized. Finally, we propose the future directions of Mn bioremediation by microbes. Conclusively, this review provides a scientific basis for the microbial remediation performance for Mn pollution and guides the development of a comprehensive competent strategy towards practical Mn remediation.
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OBJECTIVE: To investigate the regulatory effect of miRNA-29a-3p (miR-29a-3p ) on hepatoma-derived growth factor (HDGF), and its influences on the proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell line E6-1. METHODS: Thirty-five patients with ALL treated in our hospital from January 2017 to January 2019 were selected as research objects, and 35 adults who underwent physical examination in the same period were selected as healthy control group. The miR-29a-3p overexpression vector, miR-29a-3p inhibitory expression vector, and miR-29a-3p and HDGF co-overexpression vector were transfected into E6-1 cells. The expression levels of miR-29a-3p and HDGF mRNA were detected by RT-qPCR. The expression of protein was detected by Western blot. The targeting relationship between miR-29a-3p and HDGF was detected by dual luciferase reporter assay. The cell proliferation was detected by CCK-8 method, while apoptosis detected by flow cytometry. RESULTS: Compared with healthy control group, HDGF was highly expressed in serum of patients with ALL and leukemia cells HuT 78, E6-1, CCRF-CEM, while miR-29a-3p was low expressed (P<0.05). After overexpression of miR-29a-3p , the expression levels of CyclinD1 and Bcl-2 in leukemia cells E6-1 were significantly reduced, while the expression levels of p21 and Bax were significantly increased (P<0.05). The activity of E6-1 cells was also significantly reduced, while the apoptosis rate of E6-1 cells was significantly increased (P<0.05). miR-29a-3p could target and regulate the expression of HDGF, while overexpression of HDGF reversed the inhibitory effect of miR-29a-3p overexpression on the proliferation and promotion effect on the apoptosis of leukemia cells E6-1. CONCLUSION: Overexpression of miR-29a-3p can inhibit the proliferation and promote the apoptosis of ALL cells E6-1, and its mechanism may be related to the regulation of HDGF expression.
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Leucemia , MicroARNs , Humanos , Apoptosis , Proliferación Celular , MicroARNs/genéticaRESUMEN
Endometriosis (EMs) is a benign disease with the characteristics of invasion and migration, and its pathogenesis is related to hypoxia. The abnormal activation of glioma-associated oncogene homolog 1 (GLI1) plays an important role in the metastasis of multiple types of tumors. However, it is not clear whether GLI1 regulates the migration and invasion of endometrial stromal cells under hypoxic condition. Therefore, we use comprehensive analysis to explore the effects of hypoxic on GLI1 expression and their regulation on the pathogenesis of EMs. In this study, from immunohistochemistry, RT-qPCR, and western blot analysis, we discovered that the expression of hypoxia-induced factor-1α (HIF-1α) and GLI1 was significantly increased in eutopic and ectopic endometrium of patients with EMs. In human primary eutopic endometrial stromal cells (ESCs), hypoxia can increase the expression of HIF-1α and GLI1 in a time-dependent manner. And hypoxia could promote GLI1 expression in a HIF-1α-dependent manner. Moreover, data from transwell assays manifested that the migration and invasion ability of ESCs was significantly enhanced under hypoxia, and this effect could be reversed by silencing GLI1. Furthermore, the expression of MMP2 and MMP9 was also increased under hypoxia, while silencing GLI1 could reverse this event. In summary, our research verified that GLI1, which activated by hypoxia, may contribute to the migration and invasion of ESCs through the upregulation of MMP2 and MMP9 and can be a novel therapeutic target in EMs.
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Endometriosis , Femenino , Humanos , Endometriosis/genética , Endometriosis/metabolismo , Endometriosis/patología , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/farmacología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/farmacología , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/farmacología , Movimiento Celular/genética , Células Cultivadas , Células del Estroma/metabolismo , Células del Estroma/patología , Hipoxia/metabolismo , Hipoxia/patologíaRESUMEN
BACKGROUND: Percutaneous vertebroplasty (PVP) is a common procedure, but cement leaks are not uncommon. Leakages do not always have consequences, but rarely complications do occur. Spinal subdural hematomas (sSDHs) are rare and even rarer presented as a complication after PVP. The best management for sSDH is, therefore, difficult to decide. OBSERVATIONS: The patient first received PVP for acute low back pain after falling. Cement leakages were noted after the procedure, but a sudden new-onset leg weakness only developed later. An emergency lumbar computed tomography scan showed cement leakages anterior to the dural sac; lumbar magnetic resonance imaging revealed a subdural spinal hematoma, and a decompressive laminectomy was performed. During the operation, a small cement mass in the shape of a horn was seen and was believed to have caused the sSDH. Postoperatively, the patient recovered to leg strength 5/5. LESSONS: PVP is considered a low-risk procedure, and cement leaks rarely give rise to complications. However, when leakages present anterior to the dural sac, they may cause dural tear and possible sSDH, regardless of size. This possibility draws attention to keeping awareness of such rare but possible complications after routine PVP procedures. Timely intervention for sSDH is necessary to ensure meaningful recovery.
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OBJECTIVE: The study investigated our institutional learning curve for the ROSA ONE spine system (ROSA) based on ROSA usage time. METHODS: ROSA was designed to provide high accuracy for spinal pedicle screw placement through a built-in tracking technique. This study was conducted from November 2018 to January 2021. The time taken to complete each step of the robotic workflow was recorded. Patient demographics, comorbidities, surgical indications, and number of screw placements were examined in subgroup analysis. The Curve Fitting-General package (a part of NCSS 2021 software) was used to fit a mathematical model to the learning curve. Patient demographics, imaging data, and surgical time were reviewed retrospectively. RESULTS: A total of 167 patients who had undergone surgery were included. The mean total ROSA usage time was 107.1 ± 27.3 minutes. The estimated learning rate was 90.4%, and the largest slope change occurred close to the time of the 20th surgery. The observed overall learning trend in the 4-screw group could be attributed to screw planning. The presence of scoliosis (p = 0.73) or spondylolisthesis (p = 0.70) did not significantly influence the mean total time (TT) for all patients; however, the mean TT differed significantly (p < 0.01) among subgroups stratified by body mass index, screw number placement, and thoracic spine involvement. CONCLUSION: To the best of our knowledge, this is the first study to examine the learning curve for the various crucial steps of ROSA-guided pedicle screw placement. The indicative learning curve involved 20 patients who had undergone surgery.
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OBJECTIVE: The use of robotics in spinal surgery has gained popularity because of its promising accuracy and safety. ROSA is a commonly used surgical robot system for spinal surgery. The aim of this study was to compare outcomes between robot-guided and freehand fluoroscopy-guided instrumentation in minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF). METHODS: This retrospective consecutive series reviewed 224 patients who underwent MIS-TLIF from March 2019 to April 2020 at a single institution. All patients were diagnosed with degenerative pathologies. Of those, 75 patients underwent robot-guided MIS-TLIF, and 149 patients underwent freehand fluoroscopy-guided MIS-TLIF. The incidences of pedicle breach, intraoperative outcomes, postoperative outcomes, and short-term pain control were compared. RESULTS: The patients who underwent robot-guided surgery had a lower incidence of pedicle breach (0.27% vs 1.75%, p = 0.04) and less operative blood loss (313.7 ± 214.1 mL vs 431.6 ± 529.8 mL, p = 0.019). Nonsignificant differences were observed in operative duration (280.7 ± 98.1 minutes vs 251.4 ± 112.0 minutes, p = 0.056), hospital stay (6.6 ± 3.4 days vs 7.3 ± 4.4 days, p = 0.19), complications (intraoperative, 1.3% vs 1.3%, p = 0.45; postoperative surgery-related, 4.0% vs 4.0%, p = 0.99), and short-term pain control (postoperative day 1, 2.1 ± 1.2 vs 1.8 ± 1.2, p = 0.144; postoperative day 30, 1.2 ± 0.5 vs 1.3 ± 0.7, p = 0.610). A shorter operative duration for 4-level spinal surgery was found in the robot-guided surgery group (388.7 ± 107.3 minutes vs 544.0 ± 128.5 minutes, p = 0.047). CONCLUSIONS: This retrospective review revealed that patients who underwent robot-guided MIS-TLIF experienced less operative blood loss. They also benefited from a shorter operative duration with higher-level (> 3 levels) spinal surgery. The postoperative outcomes were similar for both robot-guided and freehand fluoroscopy-guided procedures.