Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 296
Filtrar
1.
Sci Rep ; 14(1): 22775, 2024 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353993

RESUMO

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Receptor ErbB-2 , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Prognóstico , Feminino , Masculino , Metilação de DNA , Pessoa de Meia-Idade , Estimativa de Kaplan-Meier , Idoso , Curva ROC
2.
Discov Oncol ; 15(1): 501, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331302

RESUMO

Glioblastoma (GBM), a primary brain tumor, exhibits remarkable invasiveness and is characterized by its intricate location, infiltrative behavior, the presence of both the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), phenotypic diversity, an immunosuppressive microenvironment with limited development yet rich vascularity, as well as the resistant nature of glioblastoma stem cells (GSCs) towards traditional chemotherapy and radiotherapy. These formidable factors present substantial obstacles in the quest for effective GBM treatments. Following extensive research spanning three decades, the hepatocellular receptor A2 (EphA2) receptor tyrosine kinase has emerged as a promising molecular target with translational potential in the realm of cancer therapy. Numerous compounds aimed at targeting EphA2 have undergone rigorous evaluation and clinical investigation. This article provides a comprehensive account of the distinctive roles played by canonical and non-canonical EphA2 signaling in various contexts, while also exploring the involvement of the EphA2-ephrin A1 signaling axis in GBM pathogenesis. Additionally, the review offers an overview of completed clinical trials targeting EphA2 for GBM treatment, shedding light on both the prospects and challenges associated with EphA2-directed interventions in the domain of cancer therapeutics.

3.
Int J Biol Macromol ; 280(Pt 2): 135903, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39313059

RESUMO

Straw is an abundant renewable biomass resource material. Lignin contained in straw is a unique natural aromatic compound in nature. At present, it is urgent to find ways to realize the higher value of natural lignin resources. In this study, alkali lignin was separated from rice straw by hydrothermal method in NaOH solution, which was prepared lignin nanoparticles by a simple green anti-solvent method. The obtained lignin nanoparticles had excellent anti-tyrosinase activity (IC50 = 0.329 mg mL-1) and anti-oxidation performance (IC50 = 0.0451 mg mL-1). Meanwhile, through the analysis of tyrosinase inhibition kinetics, it is concluded that the tyrosinase inhibition by lignin nanoparticles belongs to mixed inhibition. The affinity of lignin nanoparticles to the free enzyme is greater than that of enzyme and substrate complex. In addition, lignin nanoparticles were added to chitosan solution for compounding, then the composite films for fruit preservation were prepared by casting method. The experimental results show that the composite membrane can effectively extend the shelf life of fruits, which is expected to achieve a broader application in the field of fruit preservation and food packaging.

4.
Front Pharmacol ; 15: 1450238, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295935

RESUMO

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAH-induced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis.

5.
Mol Med Rep ; 30(5)2024 11.
Artigo em Inglês | MEDLINE | ID: mdl-39239742

RESUMO

The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system­related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed.


Assuntos
Neoplasias do Sistema Digestório , Tetraspaninas , Humanos , Tetraspaninas/metabolismo , Tetraspaninas/genética , Neoplasias do Sistema Digestório/metabolismo , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/patologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais
7.
Cell Commun Signal ; 22(1): 446, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327594

RESUMO

Diabetic cardiomyopathy (DCM) represents a unique myocardial disease originating from diabetic metabolic disturbances that is characterized by myocardial fibrosis and diastolic dysfunction. While recent research regarding the pathogenesis and treatment of DCM has focused primarily on myocardial cells, nonmyocardial cells-including fibroblasts, vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and immune cells-also contribute significantly to the pathogenesis of DCM. Among various therapeutic targets, fibroblast growth factor 21 (FGF21) has been identified as a promising agent because of its cardioprotective effects that extend to nonmyocardial cells. In this review, we aim to elucidate the role of nonmyocardial cells in DCM and underscore the potential of FGF21 as a therapeutic strategy for these cells.


Assuntos
Cardiomiopatias Diabéticas , Fatores de Crescimento de Fibroblastos , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/metabolismo , Humanos , Fatores de Crescimento de Fibroblastos/metabolismo , Animais , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia
8.
Nanoscale Horiz ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39224025

RESUMO

Marine biofouling severely limits the development of the marine economy, and reactive oxygen species (ROS) produced by electrocatalytic antifouling techniques could inactivate marine microorganisms and inhibit the formation of marine biofouling. Compared with an electro-Fenton reaction, a three-electron oxygen reduction reaction (3e- ORR) could generate a hydroxyl radical (˙OH) in situ without the limitation of pH and iron mud pollutants. Herein, Ov-rich γ-MnO2 is designed to enhance the 3e- ORR performance in neutral media and exhibits excellent sterilization performance for typical marine bacteria. DFT calculation reveals that Ov is beneficial to the "end-on" adsorption and activation of O2, and the Mn site could accept the electrons from *OOH and promote its further reduction to form ˙OH; Ov and Mn sites together guarantee the high 3e- ORR efficiency. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) proves the vast formation of ˙OH in the primary reaction stage, which is the key to sterilization. This work explores the reaction mechanism of the 3e- ORR in neutral media and provides the possibility for the application of electrocatalysis technology in the treatment of marine biofouling pollution.

9.
Front Oncol ; 14: 1397863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39184045

RESUMO

Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt's seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD.

10.
Brain Res Bull ; 216: 111050, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39147243

RESUMO

BACKGROUND: G protein-coupled receptor 68 (GPR68), an orphan receptor, has emerged as a promising therapeutic target for mitigating neuronal inflammation and oxidative damage. This study explores the protective mechanisms of GPR68 in cerebral ischemia-reperfusion injury (CIRI). METHODS: An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. Mice received intraperitoneal injections of Ogerin, a selective GPR68 agonist. In vitro, GPR68 was overexpressed in SH-SY5Y and HMC3 cells, and the effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cell viability were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. RESULTS: The expression of GPR68 was suppressed in cells subjected to OGD/R treatment, whereas its upregulation conferred protection to SH-SY5Y and HMC3 cells. In vivo, levels of GPR68 were reduced in brain tissues affected by MCAO/R, correlating with oxidative stress, inflammation, and neurological damage. Treatment with a GPR68 agonist decreased brain infarction, apoptosis, and dysregulated gene expression induced by MCAO/R. Mechanistically, GPR68 agonist treatment may inhibit the activation of the NF-κB/Hif-1α pathway, thereby reducing oxidative and inflammatory responses and enhancing protection against CIRI. CONCLUSIONS: This study confirms that the GPR68/NF-κB/Hif-1α axis modulates apoptosis, inflammation, and oxidative stress in CIRI, indicating that GPR68 is a potential therapeutic target for CIRI.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , NF-kappa B , Fármacos Neuroprotetores , Receptores Acoplados a Proteínas G , Traumatismo por Reperfusão , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Masculino , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Humanos , Transdução de Sinais/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Linhagem Celular Tumoral
11.
Talanta ; 280: 126764, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39197314

RESUMO

Perfluorinated compounds (PFCs), as an important class of environmental pollutants, have chemical and structural similarities that make their detection a great technical challenge. This study synthesized three species of metal-organic frameworks (MOFs) using different lanthanide metal ions or organic ligands, which were integrated into a fluorescent sensor array. This innovative approach offers a straightforward, rapid, and precise detection strategy for PFCs. Different ionization properties and fluorinated hydrophobic tails of PFCs lead to different electrostatic attraction and hydrophobic effects between PFCs and sensing elements, which become the basis for differential sensing. Furthermore, the fluorescence signal is more convenient to collect, making the sensor array simple to complete the identification. Combined with pattern recognition methods, the array successfully identified seven kinds of PFCs and mixtures with a classification accuracy of 100 % and a detection limit as low as 51 nM. Finally, the utility of the sensor array in river water sample analysis was verified. The strategy provides an effective method for identifying and determining PFCs and offers new opportunities for developing sensor arrays based on lanthanide MOFs.

12.
Int J Nanomedicine ; 19: 7775-7797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099795

RESUMO

Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.


Assuntos
Neoplasias Pulmonares , Paclitaxel , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Paclitaxel/administração & dosagem , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/farmacocinética , Flavonoides/administração & dosagem , Tamanho da Partícula , Nanopartículas/química , Camundongos , Lipossomos/química , Lipossomos/farmacocinética , Células A549 , Lipídeos/química , Masculino , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Camundongos Nus , Hemólise/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/administração & dosagem
13.
Nano Lett ; 24(26): 8071-8079, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38901035

RESUMO

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.


Assuntos
Cério , Cério/química , Polietilenoglicóis/química , Oxirredutases/química , Oxirredutases/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Polímeros/química , Indóis/química , Oxigênio/química , Oxirredução
14.
Small ; : e2403845, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940392

RESUMO

As the anode reaction of proton exchange membrane water electrolysis (PEMWE), the acidic oxygen evolution reaction (OER) is one of the main obstacles to the practical application of PEMWE due to its sluggish four-electron transfer process. The development of high-performance acidic OER electrocatalysts has become the key to improving the reaction kinetics. To date, although various excellent acidic OER electrocatalysts have been widely researched, Ir-based nanomaterials are still state-of-the-art electrocatalysts. Hence, a comprehensive and in-depth understanding of the reaction mechanism of Ir-based electrocatalysts is crucial for the precise optimization of catalytic performance. In this review, the origin and nature of the conventional adsorbate evolution mechanism (AEM) and the derived volcanic relationship on Ir-based electrocatalysts for acidic OER processes are summarized and some optimization strategies for Ir-based electrocatalysts based on the AEM are introduced. To further investigate the development strategy of high-performance Ir-based electrocatalysts, several unconventional OER mechanisms including dual-site mechanism and lattice oxygen mediated mechanism, and their applications are introduced in detail. Thereafter, the active species on Ir-based electrocatalysts at acidic OER are summarized and classified into surface Ir species and O species. Finally, the future development direction and prospect of Ir-based electrocatalysts for acidic OER are put forward.

15.
Heliyon ; 10(11): e31587, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841471

RESUMO

Aims: To provide a comprehensive bibliometric overview of drug resistance in bladder cancer (BC) from 1999 to 2022, aiming to illuminate its historical progression and guide future investigative avenues. Methods: Literature on BC drug resistance between 1999 and 2022 was sourced from the Web of Science. Visual analyses were executed using Vosviewer and Citespace software, focusing on contributions by countries, institutions, journals, authors, references, and keywords. Results: From 2727 publications, a marked growth in BC drug resistance studies was discerned over the two decades. Prominent among all institutions is the University of Texas System. The majority of top-ranked journals were American. In authorship significance, McConkey DJ led in publications, while Bellmunt J dominated in citations. Research topics predominantly spanned cancer demographics, drug efficacy evaluations, molecular features, oncology subtypes, and individualized treatment strategies, with a notable contemporary emphasis on molecular mechanisms behind drug resistance and nuances of ICIs. Conclusions: Our bibliometric analysis charts the landscape of BC drug resistance research from 1999 to 2022. While the study of resistance mechanisms has been robust, there's an evident need for deeper exploration into the molecular intricacies and the potential of ICIs and targeted therapeutic strategies.

16.
Front Neurol ; 15: 1284038, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872820

RESUMO

Background: Falcotentorial meningiomas (FM) are surgical challenges for protecting sinus, and the technique notes on the management of superior sagittal or transverse sinus are required for good results. Methods: We improved the technique notes on the management of superior sagittal or transverse sinus in three FM patients with signs of increased intracranial pressure or chronic headache. Results: All patients underwent surgeries in the prone position, and occipital/sup-occipital/sub-occipital craniotomy was performed. In one patient, the skull was removed traditionally with exposure of the confluence of sinuses, superior sagittal, and transverse sinus, while the longitudinal skull bridge was left to suspend the dura for protecting the superior sagittal sinus in one patient, and the transverse skull bridge was left to suspend the dura for protecting the transverse sinus in one patient. The dura was opened infratentorially or supratentorially to spare the sinus and then the "skull bridge" was suspended. The tumor was then removed completely without brain swelling or significant venous bleeding. Complete tumor resection was confirmed by early postoperative imaging, and all patients recovered well without postoperative morbidity. Conclusion: The authors recommend the "skull bridge" to suspend the dura for optimal control of the venous sinuses during FM surgery (less venous bleeding).

17.
J Integr Plant Biol ; 66(7): 1385-1407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38818952

RESUMO

The heading date of rice is a crucial agronomic characteristic that influences its adaptability to different regions and its productivity potential. Despite the involvement of WRKY transcription factors in various biological processes related to development, the precise mechanisms through which these transcription factors regulate the heading date in rice have not been well elucidated. The present study identified OsWRKY11 as a WRKY transcription factor which exhibits a pivotal function in the regulation of the heading date in rice through a comprehensive screening of a clustered regularly interspaced palindromic repeats (CRISPR) ‒ CRISPR-associated nuclease 9 mutant library that specifically targets the WRKY genes in rice. The heading date of oswrky11 mutant plants and OsWRKY11-overexpressing plants was delayed compared with that of the wild-type plants under short-day and long-day conditions. Mechanistic investigation revealed that OsWRKY11 exerts dual effects on transcriptional promotion and suppression through direct and indirect DNA binding, respectively. Under normal conditions, OsWRKY11 facilitates flowering by directly inducing the expression of OsMADS14 and OsMADS15. The presence of elevated levels of OsWRKY11 protein promote formation of a ternary protein complex involving OsWRKY11, Heading date 1 (Hd1), and Days to heading date 8 (DTH8), and this complex then suppresses the expression of Ehd1, which leads to a delay in the heading date. Subsequent investigation revealed that a mild drought condition resulted in a modest increase in OsWRKY11 expression, promoting heading. Conversely, under severe drought conditions, a significant upregulation of OsWRKY11 led to the suppression of Ehd1 expression, ultimately causing a delay in heading date. Our findings uncover a previously unacknowledged mechanism through which the transcription factor OsWRKY11 exerts a dual impact on the heading date by directly and indirectly binding to the promoters of target genes.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Fatores de Transcrição , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Mutação/genética , Flores/genética , Flores/metabolismo , Plantas Geneticamente Modificadas/genética
18.
J Chem Phys ; 160(19)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38752533

RESUMO

Ion hydration plays a crucial role in numerous fundamental processes. Various spectroscopic methods are employed to investigate the slowing down of hydration bond dynamics in the proximity of both anions and cations. To date, most of these studies have primarily focused on the properties of binary systems. However, in comparison to ion-water binary systems, ternary systems that involve ions, water, and organic matter are more prevalent in nature and provide more realistic insights into biological processes. This study focuses on ion hydration in water and alcohol mixture using terahertz spectroscopy and x-ray diffraction (XRD). The results reveal a distinct behavior depending on the type of alcohol used. Specifically, the presence of both methanol and ethanol results in the disappearance of absorption peaks associated with NaCl hydrate at low temperatures. In contrast, tert-butanol does not exhibit such an effect, and isopropanol demonstrates a more complex response. By combining these terahertz spectroscopic findings with low-temperature XRD data, we gain insights into the formation, or lack thereof, of NaCl · 2H2O hydrate crystals. Crucially, our observations suggest a dominant correlation between the polarity of the alcohol molecules and its impact on the Na+ hydration. Strongly polar alcohols preferentially solvating the Na+ ion lead to the failure of hydrate formation, while weakly polar alcohols do not have this effect.

19.
Am J Cancer Res ; 14(3): 1419-1432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590411

RESUMO

The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.

20.
J Colloid Interface Sci ; 668: 293-302, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38678885

RESUMO

Understanding the cytotoxicity of fluorescent carbon dots (CDs) is crucial for their applications, and various biochemical assays have been used to study the effects of CDs on cells. Knowledge on the effects of CDs from a biophysical perspective is integral to the recognition of their cytotoxicity, however the related information is very limited. Here, we report that atomic force microscopy (AFM) can be used as an effective tool for studying the effects of CDs on cells from the biophysical perspective. We achieve this by integrating AFM-based nanomechanics with AFM-based imaging. We demonstrate the performance of this method by measuring the influence of CDs on living human neuroblastoma (SH-SY5Y) cells at the single-cell level. We find that high-dose CDs can mechanically induce elevated normalized hysteresis (energy dissipation during the cell deformation) and structurally impair actin skeleton. The nanomechanical change highly correlates with the alteration of actin filaments, indicating that CDs-induced changes in SH-SY5Y cells are revealed in-depth from the AFM-based biophysical aspect. We validate the reliability of the biophysical observations using conventional biological methods including cell viability test, fluorescent microscopy, and western blot assay. Our work contributes new and significant information on the cytotoxicity of CDs from the biophysical perspective.


Assuntos
Carbono , Sobrevivência Celular , Microscopia de Força Atômica , Pontos Quânticos , Humanos , Carbono/química , Pontos Quânticos/química , Sobrevivência Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/citologia , Neurônios/metabolismo , Linhagem Celular Tumoral , Tamanho da Partícula , Propriedades de Superfície , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Actinas/metabolismo , Actinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...