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1.
ACS Appl Bio Mater ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083038

RESUMO

Ischemic stroke, as a prevalent neurological disorder, often results in rapid increases in the production of reactive oxygen species (ROS) and inflammatory factors in the focal ischemic area. Though edaravone is an approved treatment, its effect is limited due to its weak ability to cross the blood-brain barrier (BBB) and short half-life. Other effective pharmacological treatment options are clearly lacking. In this study, PNIVDBrF-3-Eda (also named MG-3-Eda) was prepared using a thermo- and pH dual-responsive PNIVDBrF microgel. These were designed with a positively charged network, as synthesized by simultaneous quaternization cross-linking and surfactant-free emulsion copolymerization, to be loaded with the negatively charged edaravone. We then investigated whether such a targeted delivery of edaravone could provide enhanced neuroprotection. Cytotoxicity assays confirmed that the microgel (<1 mg/mL) exhibited promising cytocompatibility with no remarkable effect on cell viability, cell cycle regulation, or apoptosis levels. In vitro and in vivo experiments demonstrated that the microgels could successfully penetrate the blood-brain barrier where efficient BBB crossing was observed after disruption of the BBB due to ischemic injury. This enabled MG-3-Eda to target the cerebral ischemic area and achieve local release of edaravone. Treatment with MG-3-Eda significantly reduced the cerebral infarct area in transient middle cerebral artery occlusion (tMCAO) mice and significantly improved behavioral scores. MG-3-Eda treatment also prevented the reduction in NF200 expression, a neuronal marker protein, and attenuated microglia activation (as detected by Iba1) in the local ischemic area via local antioxidant and anti-inflammatory effects. A superior neuroprotective effect was noted for MG-3-Eda compared to that for free edaravone. Our results indicate that MG-3-Eda administration represents a clear potential treatment for cerebral ischemia via its targeted delivery of edaravone to ischemic areas where it provides significant local antioxidant and anti-inflammatory effects.

2.
Adv Clin Exp Med ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083254

RESUMO

Long non-coding RNAs are RNA molecules with a transcript length of more than 200 nucleotides and without protein-coding ability. They regulate gene expression by interacting with protein, RNA and DNA. Their function is closely related to their subcellular localization, with regulation of gene expression at the epigenetic and transcriptional levels occurring in the nucleus, and at the post-transcriptional and translational levels in the cytoplasm. Long stress-induced non-coding transcript 5 (LSINCT5), which is localized in the nucleus, is overexpressed in many types of cancers such as breast cancer, gastric cancer, ovarian cancer, thyroid cancer, and gastrointestinal cancer. Substantial evidence indicates that there is an obvious connection between cancers and LSINCT5, as it inhibits apoptosis and promotes proliferation, invasion and migration of cancer cells, as well as participates in the pathogenesis and progression of cancer by interacting with DNA, protein and RNA. These findings suggest that LSINCT5 could be a novel biomarker and an emerging therapeutic target in human cancers. In the present study, the structure and corresponding biological function of LSINCT5 were summarized in order to clarify its molecular mechanisms in the progression of various malignant tumors.

3.
PeerJ ; 10: e13692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071827

RESUMO

Background: The presence of alveolar epithelial type II cells (AECIIs) is one of the most important causes of bronchopulmonary dysplasia (BPD). Exosomes from bone mesenchymal stem cells (BMSCs) can reduce hyperoxia-induced damage and provide better results in terms of alveolar and pulmonary vascularization parameters than BMSCs. Currently, intervention studies using BMSC-derived exosomes on the signaling pathways regulating proliferation and apoptosis of alveolar epithelial cells under the condition of BPD have not been reported. This study investigated the effects of rat BMSC-derived exosomes on the proliferation and apoptosis of hyperoxia-induced primary AECIIs in vitro. Methods: The isolated AECIIs were grouped as follows: normal control (21% oxygen), hyperoxia (85% oxygen), hyperoxia+exosome (20 µg/mL), hyperoxia+exosome+LY294002 (PI3K/Akt inhibitor, 20 µM), and hyperoxia+exosome+rapamycin (mTOR inhibitor, 5 nM). We used the PI3K/Akt inhibitor LY294002 and the mTOR inhibitor rapamycin to determine the roles of the PI3K/Akt and mTOR signaling pathways. The effects of BMSC-derived exosomes on AECII proliferation and apoptosis were assessed, respectively. Results: Decreased levels of the antiapoptotic protein Bcl-2, the cell proliferation protein Ki67, p-PI3K, p-Akt, and p-mTOR, as well as increased levels of AECII apoptosis and the proapoptotic protein Bax in the hyperoxia group were observed. Notably, Sprague Dawley rat BMSC-derived exosomes could reverse the effect of hyperoxia on AECII proliferation. However, the application of LY294002 and rapamycin inhibited the protective effects of BMSC-derived exosomes. Conclusion: Our findings revealed that BMSC-derived exosomes could regulate the expression of apoptosis-related proteins likely via the PI3K/Akt/mTOR signaling pathway, thereby preventing hyperoxia-induced AECII apoptosis.

4.
Pract Radiat Oncol ; 12(5): 397-408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36058618

RESUMO

PURPOSE: To estimate the variations in clinical target volumes (CTVs) and organs at risk delineation within the quality assurance (QA) program of the POTENTIAL trial, which is a multicenter, randomized phase 3 trial evaluating postmastectomy radiation therapy (RT), with or without internal mammary nodal irradiation, for patients with high-risk breast cancer. METHODS AND MATERIALS: The simulating computed tomography scan data set of a benchmark case was sent to the participating centers, and the delineation of CTVs and organs at risk was required to be completed by the investigators following protocol guidelines. All submitted contours were reviewed and compared with the reference contours created by the QA team, using quantitative geometric analysis regarding volume and the Jaccard Index (JCI), Dice similarity coefficient, Geographic Miss Index, Discordance Index, and mean distance to agreement. In addition to the whole-volume analysis of all structures, the combination contour of the supraclavicular fossa and level III and II axilla (CTVsc + axIII + axII) was further analyzed on a slice-by-slice basis. RESULTS: The contours from 26 centers were reviewed and variations were observed between submission and reference. The variations of the CTV of the chest wall, contralateral breast, and heart were small, for which the mean JCI values were 0.62, 0.68, and 0.87, respectively. However, the mean JCI values of the CTV of the internal mammary nodal region, ipsilateral brachial plexus, left anterior descending coronary artery, and right coronary artery were 0.38, 0.21, 0.29, and 0.18, respectively, suggesting marked variations. In addition, marked under- and overoutlining variations were identified on 4 slices of CTVsc + axIII + axII on slice-by-slice analysis. CONCLUSIONS: There were residual contouring variations despite a detailed protocol being provided, confirming the importance of pretrial QA in RT and highlighting the need for education and consideration of a real-time central review of the target delineation before the trial participants begin RT.


Assuntos
Neoplasias da Mama , Órgãos em Risco , Benchmarking , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos
5.
J Environ Public Health ; 2022: 1734008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060871

RESUMO

Based on the conceptual model of the black-box deconstruction of dynamic sustainable development ability driving environmental performance of manufacturing enterprises, the nonparametric percentile bootstrap method based on deviation correction is used to demonstrate the theoretical hypothesis and empirically deconstruct the black-box of dynamic sustainable development driving environmental performance. Empirical results show that (1) dynamic sustainable development ability has a positive influence on environmental performance; (2) green resource integration ability, green duality, low-carbon manufacturing practice, and green intelligence capital play mediating roles in the influence of dynamic sustainable development ability on environmental performance; and (3) environmental regulation positively moderates the mediating mechanism of green resource integration ability, green duality, low-carbon manufacturing practice, and green intelligence capital of the relationships between dynamic sustainable development ability and environmental performance.


Assuntos
Condução de Veículo , Desenvolvimento Sustentável , Carbono , China
6.
Innovation (Camb) ; 3(5): 100300, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36051818
7.
Biomed Pharmacother ; 153: 113498, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076588

RESUMO

The present study aimed to explore the role of oxytocin (OT) in myocardial injury induced by ischemia/reperfusion (I/R) and hyperglycemia and its underlying mechanisms. In this study, the isolated rat hearts underwent I/R in Langendorff perfusion model and H9c2 cells were subjected to hypoxia/reoxygenation (H/R) to establish an in vitro model. I/R injury was induced by exposing the rat hearts to 40 min of global ischemia followed by 60 min of reperfusion. H9c2 cells were cultured under the normoglycemic or hyperglycemic condition with or without pretreatment of OT, and then exposed to 4 h of hypoxia and 2 h of reoxygenation. Measurement indicators included myocardial infarct size assessed by triphenyltetrazolium chloride (TTC) staining and hemodynamic parameters in the ex vivo model as well as cell viability detected by cell counting kit 8 (CCK-8), apoptotic rate evaluated by flow cytometry, and the protein expressions by Western blot. The findings demonstrated that OT attenuated myocardial I/R injury. First, OT preconditioning significantly reduced hemodynamic disorders and myocardial infarct sizes. In addition, OT increased cell viability, decreased cell apoptosis and the expressions of IL-18, IL-1ß, cleaved-caspase-1, NLRP3, and GSDMD following H/R. NLRP3 activator nigericin eliminated the beneficial effects of OT in H9c2 cells. Furthermore, OT also activated AMPK and decreased the expressions of pyroptosis-related proteins. Administration of AMPK inhibitor compound C blunted OT-induced AMPK phosphorylation and elevated the expressions of pyroptosis-related proteins in H9c2 cells subjected to H/R with hyperglycemia. OT alleviates myocardial I/R injury with hyperglycemia by inhibiting pyroptosis via AMPK/NLRP3 signaling pathway.


Assuntos
Hiperglicemia , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glucose/metabolismo , Hiperglicemia/metabolismo , Hipóxia/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ocitocina/farmacologia , Piroptose , Ratos , Reperfusão , Transdução de Sinais
8.
Abdom Radiol (NY) ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088602

RESUMO

OBJECTIVE: To evaluate the accuracy of contrast-enhanced (CE) fat-suppressed three-dimensional (3D) T1-weighted imaging with volumetric interpolated breath-hold examination (FS-T1-3D-VIBE) and fat-suppressed T1-weighted turbo spin echo (FS-T1-TSE) sequence in characteristics of anal fistula. METHODS: One hundred and two patients underwent perianal CE-MRI examination on a 3T scanner including FS-T1-3D-VIBE and FS-T1-TSE sequences before surgery. The performance of each sequence was evaluated in terms of fistula classification, clarity of internal opening, number and position of internal openings including the distance between internal opening and anal verge, presence of secondary tracts and blind-ending sinus tracts. MRI findings were compared with surgical findings. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of fistula, gluteus maximus, and subcutaneous fat were compared between CE FS-T1-TSE and CE FS-T1-3D-VIBE. RESULTS: Compared with CE FS-T1-TSE, CE FS-T1-3D-VIBE displayed more accurate in secondary tract, lithotomy position of the internal opening and the distance between internal opening and anal verge (P < 0.05). CE FS-T1-3D-VIBE was found superior to CE FS-T1-TSE in the clarity of the internal openings and in the diagnostic accuracy of blind-ending sinus tracts and complex fistulas in Standard Practice Task Force classification (P < 0.05). CE FS-T1-3D-VIBE achieved higher SNRs and CNRs in fistula and gluteus maximus than CE FS-T1-TSE (P ≤ 0.001). CONCLUSION: CE-MRI of FS-T1-3D-VIBE might be a more valuable noninvasive technique than FS-T1-TSE to evaluate the anal fistula on evaluating the lithotomy position of internal opening, distance between internal opening and anal verge, clarity of internal opening, secondary tract, blind-ending sinus tract and classification of the complex fistula. The trial registration number for this prospective trial was Chi-TR1800020206 and the trial registration date was December 20, 2018.

9.
J Cell Mol Med ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065764

RESUMO

Academics generally believe that imbalance between excitation and inhibition of the nervous system is the root cause of epilepsy. However, the aetiology of epilepsy is complex, and its pathogenesis remains unclear. Many studies have shown that epilepsy is closely related to genetic factors. Additionally, the involvement of a variety of tumour-related transcription factors in the pathogenesis of epilepsy has been confirmed, which also confirms the heredity of epilepsy. In this review, we summarize the existing research on a variety of transcription factors and epilepsy and present relevant evidence related to transcription factors that may be targets in epilepsy. This information is of great significance for revealing the in-depth molecular and cellular mechanisms of epilepsy.

10.
Hum Mutat ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36054333

RESUMO

Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole-genome sequencing (WGS) data of 140 isolated spina bifida cases and identified eight missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased the FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants downregulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.

11.
Psychiatry Res ; 317: 114823, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36084542

RESUMO

This study aimed to analyze the use of antidepressants in non-psychiatric departments. The data of patients treated with antidepressants in non-psychiatric departments of the First Affiliated Hospital of Xi 'an Jiaotong University, were collected from 2014 to 2018. The average annual growth rate of antidepressants use was 22.83%. According to the number of patients at discharge, the classification descending order was: SSRIs, Flupenthixol-TCA, SNRIs, TCAs, SARIs, and NaSSA. Sertraline and flupenthixol-melitracen were the main drugs used in SSRIs and Flupenthixol-TCA, respectively. Neurology, Cardiology, and Geriatrics were the main departments prescribing SSRIs, Flupenthixol-TCA and SNRIs. The antidepressants used by all patients were mainly SSRIs according to drug classification, but the specific drug use in unclear diagnosis group was dominated by flupenthixol-melitracen, while it was sertraline in clear diagnosis group. The proportion of Flupenthixol-TCA in anxiety state group was higher than that in depression state group, While the situation in SSRIs is the opposite. More guidelines should be formulated to improve the recognition of comorbidities between specialized diseases and psychiatric disorders. Also, multi-level training should be implemented to perform the standard diagnosis and medication of mental disorders in clinical practice.

12.
J Enzyme Inhib Med Chem ; 37(1): 2530-2539, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36100238

RESUMO

A series of litseaone B analogues 4a∼4p were synthesised and antitumor activities of all compounds were screened. These compounds were designed by introducing different substituents on the B ring. Among these synthesised compounds, it was proved that 4k showed excellent activity against A549, HepG2, and HCT-15 cell lines, the IC50 values were 7.60 µM, 20.53 µM, and 4.59 µM, respectively. The results of tubulin polymerisation inhibition and immunofluorescence staining experiments displayed that 4k could act on tubulin and inhibit the polymerisation of tubulin. Moreover, the wound healing assay showed that 4k could inhibit the migration of A549 cells in a dose-dependent manner. Furthermore, the results of flow cytometry revealed that 4k was capable of blocking the cell cycle in the G2/M phase, inducing a decrease in the mitochondrial membrane potential and ultimately leading to apoptosis in A549 cells. Importantly, the possible binding model was also performed by molecular docking. Subject classification codes: short communication.


Assuntos
Moduladores de Tubulina , Tubulina (Proteína) , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides , Simulação de Acoplamento Molecular , Tubulina (Proteína)/metabolismo
13.
iScience ; 25(9): 105012, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36093047

RESUMO

This study surveyed 669 plant scientists globally to elicit how (which outcomes of gene editing), where (which continent) and what (which crops) are most likely to benefit from CRISPR research and if there is a consensus about specific barriers to commercial adoption in agriculture. Further, we disaggregated public and private plant scientists to see if there was heterogeneity in their views of the future of CRISPR research. Our findings suggest that maize and soybeans are anticipated to benefit the most from CRISPR technology with fungus and virus resistance the most common vehicle for its implementation. Across the board, plant scientists viewed consumer perception/knowledge gap to be the most impeding barrier of CRISPR adoption. Although CRISPR has been hailed as a technology that can help alleviate food insecurity and improve agricultural sustainability, our study has shown that plant scientists believe there are some large concerns about the consumer perceptions of CRISPR.

14.
Biomed Res Int ; 2022: 9545609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093399

RESUMO

ALDH+ H1975 lung adenocarcinoma stem cells (LSCs) are a rare cell population identified in lung adenocarcinoma (LUAD). LSCs can self-renew, drive tumor initiation, growth, metastasis, and recurrence and are also the predominant cause of poor prognosis due to their intrinsic resistance to drugs and chemotherapy. Consequently, LSCs are a promising target for LUAD therapy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), exert many significant regulatory functions in the pathogenesis of human cancers, showing the necessity for a comprehensive understanding of the mechanisms that underlie lung carcinogenesis. Nonetheless, research on many known transcripts and messenger RNAs (mRNAs) has already generated new information. Unknown biomarkers in ncRNAs and systematic and comprehensive interrelation with unknown ncRNAs and mRNAs may provide further insights into the biology of LUAD. Herein, a set of novel ncRNAs that include miRNAs, lncRNAs, and circRNAs were identified, and differentially expressed patterns of ncRNAs and mRNAs in LSCs and ALDH-H1975 LUAD tumor cells (LTCs) were obtained using stringent bioinformatics pipelines. Through a meta-analysis of the identified landscapes, novel competitive endogenous RNA (ceRNA) networks were constructed to reveal the potential molecular mechanisms that regulate the hallmarks of LSCs and LTCs. This study presents a summary of novel ncRNAs and the fundamental roles of differentially expressed ncRNAs implicated in the activity of LSCs and LTCs. In addition, the study also provides a comprehensive resource for the future identification of diagnostic, therapeutic, and prognostic biomarkers in LUAD.


Assuntos
Adenocarcinoma , MicroRNAs , RNA Longo não Codificante , Adenocarcinoma/genética , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Pulmão/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/genética , Células-Tronco/metabolismo
15.
Turk J Gastroenterol ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098359

RESUMO

BACKGROUND: Interleukin-17A is a proinflammatory cytokine that is produced by TH17 cells, and plays a dual role in tumor progression, infectious diseases, and autoimmune disorders. Interleukin-17A is induced during colorectal tumorigenesis and angiogenesis, although some studies have reported an anti-tumor effect as well. The aim of our study was to assess the prognostic role of interleukin-17A in colorectal cancer and determine the potential mechanisms. METHODS: The GEO database was searched using the keyword "colorectal cancer", and 10 datasets were identified that included interleukin-17A mRNA expression and survival data of several colorectal cancer patient cohorts. The patients were stratified into the interleukin-17Ahigh and interleukin-17Alow groups based on the median expression level. RESULTS: Higher interleukin-17A mRNA levels were associated with better overall survival rates and the early tumor stage, indicating a protective role of interleukin-17A in colorectal cancer. Furthermore, interleukin-17A mRNA expression also correlated positively with that of TNFS11, CCR6, and CCL20, indicating that the anti-tumor effect of interleukin-17A is likely mediated by enhancing tumor antigen presentation by dendritic cells and recruiting the activated tumor-specific CD8+ cytotoxic T lymphocytes. The IL-23 and STAT3 mRNA levels were also significantly higher in the interleukin-17Ahigh group, which points to an upstream regulatory role of IL-23/STAT3 axis. Finally, the immune checkpoints PDCD1 (PD-1) and CD274 (PDL-1) were also positively correlated with interleukin-17A mRNA expression, indicating that interleukin-17A is a promising predictor of the immunotherapeutic outcome of PD-1/PDL-1 blockade in colorectal cancer. CONCLUSION: Interleukin-17A mRNA is a protective factor in colorectal cancer and a promising biomarker for assessing the prognosis and immunotherapeutic response.

16.
Anal Chim Acta ; 1228: 340334, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36127002

RESUMO

Ochratoxin A (OTA) has been classified as a possible human carcinogen and accurate monitoring of OTA is crucial for avoiding the contaminant risk. Herein, a sensitive biosensor for OTA detection was reported. This biosensor achieved a lower detection limit of 0.026 ng/mL with the linear range of 0.03-50 ng/mL, owning to the coordination of the structure-switching of the aptaswitch and bioorthogonal capture-based signal amplification of the functionalized paper. Finally it was applied in real samples precisely and a portable device was developed for the easy readout of the fluorescent signal. Notably, this approach possessed adequate simplicity with the thorough avoidance of fluorescence plate reader or complicated material modification steps for signal amplification, and it was universally applicable by replacing the aptamer sequence in the loop instead of redesigning the structure of triple-helix aptaswitch for multifarious target analytes. Taken together, we first combined the triple-helix aptaswitch and bioorthogonal capture-based signal amplification in the detection of OTA, and this novel detection method may offer a simple, cost-effective and sensitive sensing platform for agricultural products quality monitoring.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36121200

RESUMO

Living erythrocyte (red blood cell, RBC) membranes present rich ultrastructural and dynamic details, which rely on synchronous super-resolution imaging and tracking to unveil. Yet, it poses a serious challenge to achieve the dual functions in a single probe, due to the rigid and conflicting photophysical demands of different techniques. Herein, we rationally developed a far-red boron dipyrromethene membrane probe with blinking capability and consistent single-molecule emission, and constructed a microfluidic platform for noninvasive trapping and long-term imaging of RBCs. By combining them, multi-dimensional super-resolution reconstructions and single-molecule tracking were achieved at the molecular scale on living human RBC membranes in a high-throughput manner. Our integrated system defines a quantitative method for analyzing RBC membranes under physiological and pathological conditions, improving precisions and revealing new perspectives for future disease diagnostics.

18.
Exp Gerontol ; : 111954, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122595

RESUMO

INTRODUCTION: Vitamin D - concretely its active form 1,25-dihydroxyvitamin D (1,25(OH)2D) - maintains several physiological processes. Oxylipins are oxidized lipids derived from ω-6 and ω-3 polyunsaturated fatty acids involved in inflammation. Little is known about the association of 1,25(OH)2D with inflammatory parameters in middle-aged populations - who could be at risk of vitamin D deficiency -. The aim of this study was to investigate the relationship between 1,25(OH)2D plasma levels with circulating white blood cells, platelets counts and oxylipins levels. MATERIALS AND METHODS: A total of 74 (53 % women) middle-aged (40-65 years old) adults were recruited for this cross-sectional study. 1,25(OH)2D plasma levels were measured using an immunochemiluminometric assay. White blood cells and platelets were analyzed by hemocytometry. ω-6 and ω-3 oxylipins plasma levels were measured using liquid chromatography - tandem mass spectrometry. Simple and multiple linear regression models, and Pearson correlation analysis, were performed to study the association of 1,25(OH)2D levels with WBC and platelets counts, and oxylipins, respectively. RESULTS: 1,25(OH)2D plasma levels were positively related with linoleic acid-derived oxylipins and isoprostanes plasma levels, whereas an inverse relationship with dihomo-γ-linolenic acid/linoleic acid and arachidonic acid/linoleic acid ratios was unveiled. No significant associations were observed for circulating ω-3 oxylipins, white blood cells levels or platelets count. CONCLUSIONS: Linoleic acid-derived oxylipins and isoprostanes plasma levels may be influenced by 1,25(OH)2D plasma levels. Further investigations are needed to elucidate the impact of other vitamin D forms upon circulating oxylipins levels.

19.
Chem Biol Interact ; 366: 110137, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36055377

RESUMO

Accumulating evidence have indicated that ferroptosis plays a crucial role in cerebral ischemia-reperfusion (I/R) injury which is the most serious treatment complication of ischemic stroke. Baicalein (5,6,7-trihydroxyflavone) is a main bioactive ingredient isolated from a traditional Chinese medicine named Baikal Skullcap, which is the root of Scutellaria baicalensis Georgi. This study investigated the potential role of baicalein in cerebral I/R injury using oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells, transient middle cerebral artery occlusion (tMCAO) mice and RSL3-sitmulated HT22 cells. Baicalein improved the viability of OGD/R cells and significantly ameliorated cerebral I/R injury in tMCAO mice. Baicalein decreased the iron levels, lipid peroxidation production and morphology features of ferroptosis of the brain tissues in tMCAO mice, which indicated that baicalein ameliorated cerebral I/R injury by inhibiting ferroptosis in vivo and in vitro. We further confirmed that baicalein had the activity of inhibiting ferroptosis in RSL3-stimulated HT22 cells. Western blot revealed that baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral I/R injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. The results suggested that baicalein has therapeutic potential as a drug for cerebral I/R injury.

20.
Redox Biol ; 56: 102451, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36067704

RESUMO

OBJECTIVE: Glioblastoma is one of the most common intracranial malignant tumors with an unfavorable prognosis, and iron metabolism as well as ferroptosis are implicated in the pathogenesis of glioblastoma. The present study aims to decipher the role and mechanisms of tripartite motif-containing protein 7 (TRIM7) in ferroptosis and glioblastoma progression. METHODS: Stable TRIM7-deficient or overexpressing human glioblastoma cells were generated with lentiviral vectors, and cell survival, lipid peroxidation and iron metabolism were evaluated. Immunoprecipitation, protein degradation and ubiquitination assays were performed to demonstrate the regulation of TRIM7 on its candidate proteins. RESULTS: TRIM7 expression was elevated in human glioblastoma cells and tissues. TRIM7 silence suppressed growth and induced death, while TRIM7 overexpression facilitated growth and inhibited death of human glioblastoma cells. Meanwhile, TRIM7-silenced cells exhibited increased iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by TRIM7 overexpression. Mechanistically, TRIM7 directly bound to and ubiquitinated nuclear receptor coactivator 4 (NCOA4) using K48-linked chains, thereby reducing NCOA4-mediated ferritinophagy and ferroptosis of human glioblastoma cells. Moreover, we found that TRIM7 deletion sensitized human glioblastoma cells to temozolomide therapy. CONCLUSION: We for the first time demonstrate that TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells, and our findings provide a novel insight into the progression and treatment for human glioblastoma.

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