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1.
Environ Sci Ecotechnol ; 22: 100449, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39104553

RESUMO

In recent years, there has been significant interest in photocatalytic technologies utilizing semiconductors and photosensitizers responsive to solar light, owing to their potential for energy and environmental applications. Current efforts are focused on enhancing existing photocatalysts and developing new ones tailored for environmental uses. Anthraquinones (AQs) serve as redox-active electron transfer mediators and photochemically active organic photosensitizers, effectively addressing common issues such as low light utilization and carrier separation efficiency found in conventional semiconductors. AQs offer advantages such as abundant raw materials, controlled preparation, excellent electron transfer capabilities, and photosensitivity, with applications spanning the energy, medical, and environmental sectors. Despite their utility, comprehensive reviews on AQs-based photocatalytic systems in environmental contexts are lacking. In this review, we thoroughly describe the photochemical properties of AQs and their potential applications in photocatalysis, particularly in addressing key environmental challenges like clean energy production, antibacterial action, and pollutant degradation. However, AQs face limitations in practical photocatalytic applications due to their low electrical conductivity and solubility-related secondary contamination. To mitigate these issues, the design and synthesis of graphene-immobilized AQs are highlighted as a solution to enhance practical photocatalytic applications. Additionally, future research directions are proposed to deepen the understanding of AQs' theoretical mechanisms and to provide practical applications for wastewater treatment. This review aims to facilitate mechanistic studies and practical applications of AQs-based photocatalytic technologies and to improve understanding of these technologies.

2.
Angew Chem Int Ed Engl ; : e202413102, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105615

RESUMO

Despite recent advancements in catalytic synthesis of axial chirality, reports on non-biaryl atropisomers remain limited because of the stringent steric requirements necessary to establish effective rotational brakes. In this study, we present a novel class of monoaryl atropisomers, indolyl ketosulfoxonium ylides, and describe an organocatalytic protocol for their synthesis. We discovered that a chiral phosphoric acid (CPA) serves as an effective catalyst for the highly enantioselective iodination of ortho-aminophenylethynyl sulfoxonium ylides. Under the optimized reaction conditions, a strong preference for the intended iodination process over the competing protonation was observed. Subsequently, intramolecular amide cyclization enabled the formation of sterically congested indole fragments. Furthermore, the synthetic utility of the products was demonstrated by showcasing versatile transformations into other chiral scaffolds with complete retention of optical purity.

3.
Front Cell Neurosci ; 18: 1421342, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157757

RESUMO

Introduction: Mesenchymal stem cells (MSCs) have long been postulated as an important source cell in regenerative medicine. During subculture expansion, mesenchymal stem cell (MSC) senescence diminishes their multi-differentiation capabilities, leading to a loss of therapeutic potential. Up to date, the extrachromosomal circular DNAs (eccDNAs) have been demonstrated to be involved in senescence but the roles of eccDNAs during MSC. Methods: Here we explored eccDNA profiles in human bone marrow MSCs (BM-MSCs). EccDNA and mRNA was purified and sequenced, followed by quantification and functional annotation. Moreover, we mapped our datasets with the downloading enhancer and transcription factor-regulated genes to explore the potential role of eccDNAs. Results: Sequentially, gene annotation analysis revealed that the majority of eccDNA were mapped in the intron regions with limited BM-MSC enhancer overlaps. We discovered that these eccDNA motifs in senescent BMSCs acted as motifs for binding transcription factors (TFs) of senescence-related genes. Discussion: These findings are highly significant for identifying biomarkers of senescence and therapeutic targets in mesenchymal stem cells (MSCs) for future clinical applications. The potential of eccDNA as a stable therapeutic target for senescence-related disorders warrants further investigation, particularly exploring chemically synthesized eccDNAs as transcription factor regulatory elements to reverse cellular senescence.

4.
Contact (Thousand Oaks) ; 7: 25152564241273646, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139576

RESUMO

The Synaptotagmin-like mitochondrial-lipid binding protein (SMP) domain is found in a group of ER-resident lipid transfer proteins that are recruited to membrane contact sites (MCSs) by adaptors. Deciphering the molecular basis underlying the recruitment of SMP proteins to specific MCS sheds light not only on their cellular localization but also on their biological functions at these sites. Here we summarize recent advances in SMP domain-containing lipid transfer proteins, focusing on a recent study showing the localization, regulation and cellular function of a specific SMP protein named testis expressed protein 2 (Tex2). TMEM55, a potential PIP phosphatase on late endosome/lysosomal (LE/lys) membranes, was identified as an adaptor that enables the recruitment of Tex2 to ER- LE/lys MCS. In addition, we have summarized several important questions about the regulation and physiological functions of Tex2 that remained unanswered.

5.
J Neurooncol ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39143438

RESUMO

BACKGROUND: Anoikis is a specialized form of programmed cell death induced by the loss of cell adhesion to the extracellular matrix (ECM). Acquisition of anoikis resistance is a significant marker for cancer cell invasion, metastasis, therapy resistance, and recurrence. Although current research has identified multiple factors that regulate anoikis resistance, the pathological mechanisms of anoikis-mediated tumor microenvironment (TME) in glioblastoma (GBM) remain largely unexplored. METHODS: Utilizing single-cell RNA sequencing (scRNA-seq) data and employing non-negative matrix factorization (NMF), we identified and characterized TME cell clusters with distinct anoikis-associated gene signatures. Prognostic and therapeutic response analyses were conducted using TCGA and CGGA datasets to assess the clinical significance of different TME cell clusters. The spatial relationship between BRMS1 + microglia and tumor cells was inferred from spatial transcriptome RNA sequencing (stRNA-seq) data. To simulate the tumor immune microenvironment, co-culture experiments were performed with microglia (HMC3) and GBM cells (U118/U251), and microglia were transfected with a BRMS1 overexpression lentivirus. Western blot or ELISA were used to detect BRMS1, M2 macrophage-specific markers, PI3K/AKT signaling proteins, and apoptosis-related proteins. The proliferation and apoptosis capabilities of tumor cells were evaluated using CCK-8, colony formation, and apoptosis assays, while the invasive and migratory abilities of tumor cells were assessed using Transwell assays. RESULTS: NMF-based analysis successfully identified CD8 + T cell and microglia cell clusters with distinct gene signature characteristics. Trajectory analysis, cell communication, and gene regulatory network analyses collectively indicated that anoikis-mediated TME cell clusters can influence tumor cell development through various mechanisms. Notably, BRMS1 + AP-Mic exhibited an M2 macrophage phenotype and had significant cell communication with malignant cells. Moreover, high expression of BRMS1 + AP-Mic in TCGA and CGGA datasets was associated with poorer survival outcomes, indicating its detrimental impact on immunotherapy. Upregulation of BRMS1 in microglia may lead to M2 macrophage polarization, activate the PI3K/AKT signaling pathway through SPP1/CD44-mediated cell interactions, inhibit tumor cell apoptosis, and promote tumor proliferation and invasion. CONCLUSION: This pioneering study used NMF-based analysis to reveal the important predictive value of anoikis-regulated TME in GBM for prognosis and immunotherapeutic response. BRMS1 + microglial cells provide a new perspective for a deeper understanding of the immunosuppressive microenvironment of GBM and could serve as a potential therapeutic target in the future.

6.
Fa Yi Xue Za Zhi ; 40(3): 245-253, 2024 Jun 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39166305

RESUMO

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.


Assuntos
Bibliometria , Restos Mortais , Antropologia Forense , Humanos , Antropologia Forense/métodos , Publicações/estatística & dados numéricos
7.
J Org Chem ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138971

RESUMO

On the basis of a novel umpolung strategy, an efficient l-amino acid ester-mediated in situ reduction of 2-(2-oxoindolin-3-ylidene)malononitrile and sequential nucleophilic addition/cyclization cascade reaction is reported. Various densely substituted cyclopentene bispirooxindoles and dihydrofuran bispirooxindoles with two quaternary spirocenters were constructed in high yields (≤93%) with excellent diastereoselectivities (>20:1 dr). The method has advantages of readily available starting materials, mild reaction conditions, a one-pot process, a metal-free biomimetic reducing agent, a wide substrate scope, and operational simplicity (single filtration without column chromatography).

8.
J Stroke Cerebrovasc Dis ; 33(11): 107957, 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39163950

RESUMO

OBJECT: Treatment of ruptured basilar artery trunk (BAT) aneurysms is challenging, and is associated with high complication and mortality rates. Herein, we analyzed the complications, long-term outcomes, and outcome predictors of endovascular treatment for ruptured BAT aneurysms. METHODS: Between January 2011 and July 2023, 36 patients with 36 ruptured BAT aneurysms underwent endovascular treatment at our institution. The postprocedural complications and clinical and angiographic outcomes were subsequently reviewed, and the risk factors for postprocedural complications were evaluated. RESULTS: All 36 aneurysms in 36 patients were treated successfully. The median clinical follow-up time was 47.0 (IQR: 10.5, 84.5) months. Overall, complications occurred in 10 (27.8%) patients, including 3 (8.3%) deaths. Ischemic events occurred in seven (19.4%) patients, while three (8.3%) patients had shunt-dependent hydrocephalus, of whom one (2.8%) patient had both shunt-dependent hydrocephalus and ischemic events. The cumulative survival rates at 3 and 5 years were 94.1% and 87.8%, respectively. The cumulative 3- and 5-year complication-free survival rates were 75.0% and 70.0%, respectively. Multivariate Cox regression analysis revealed that diabetes mellitus (HR:8.76, 95%CI:2.35-32.69, p=0.001), and Glasgow coma scale score ≤ 12 before the procedure (HR:5.04, 95%CI:1.40-18.12, p=0.013) were associated with overall postprocedural complications. The complete aneurysm occlusion rate was 61.5% at a median angiography follow-up time of 6.0 (IQR: 5.0, 6.0) months. CONCLUSIONS: Endovascular treatment is a safe and feasible option for treating ruptured BAT aneurysms. The rate of favorable outcomes at the final follow-up was satisfactory. However, postprocedural complications, particularly ischemic events, should be carefully considered.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39109940

RESUMO

Fibroblast growth factor 23 (FGF23) plays a crucial role in managing renal phosphate and the synthesis of 1,25(OH)2-vitamin D3, which is essential for bone homeostasis. Developing robust in vitro systems to study FGF23-regulating mechanisms is crucial for advancing our knowledge and identifying potential therapeutic targets. The traditional in vitro 2D culture system results in relatively low expression of FGF23, complicating further exploration of its regulatory mechanisms and potential therapeutic targets. Herein, we reported a high-throughput approach to generate preosteoblastic cell spheroids with enhanced FGF23 production. For this purpose, murine preosteoblast cell line (MC3T3-E1) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 92.3 ± 15.0 µm after 24 h. Compared with monolayer culture, the MC3T3-E1 spheroids showed a significant upregulation of FGF23 in both gene and protein levels after 24 h of serum-free induction. RNA sequencing and western blotting analysis further suggested that the enhanced FGF23 production in MC3T3-E1 spheroids was attributed to the activation of the parathyroid hormone (PTH)/PTH1R signaling pathway. Impressively, inhibition of PTH signaling through small molecular inhibitors or short hairpin RNA targeting PTH1R effectively reduced FGF23 production. In summary, the current study revealed the efficacy of the high-throughput formation of preosteoblast cell spheroid in stimulating FGF23 expression for mechanistic studies. Importantly, our findings highlight the potential of the current 3D spheroid system for target identification and drug discovery.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39167777

RESUMO

Ferroelectric Rashba semiconductors (FRS) are highly demanded for their potential capability for nonvolatile electric control of electron spins. An ideal FRS is characterized by a combination of room temperature ferroelectricity and a strong Rashba effect, which has, however, been rarely reported. Herein, we designed a room-temperature FRS by vertically stacking a Sb monolayer on a room-temperature ferroelectric In2Se3 monolayer. Our first-principles calculations reveal that the Sb/In2Se3 heterostructure exhibits a clean Rashba splitting band near the Fermi level and a strong Rashba effect coupled to the ferroelectric order. Switching the electric polarization direction enhances the Rashba effect, and the flipping is feasible with a low energy barrier of 22 meV. This Rashba-ferroelectricity coupling effect is robust against changes of the heterostructure interfacial distance and external electric fields. Such a nonvolatile electrically tunable Rashba effect at room temperature enables potential applications in next-generation data storage and logic devices operated under small electrical currents.

11.
Acta Pharmacol Sin ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160244

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

12.
ACS Sens ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120046

RESUMO

The metastasis of cancer cells is a principal cause of morbidity and mortality in cancer. The combination of a cytosensor and photothermal therapy (PTT) cannot completely eliminate cancer cells at one time. Hence, this study aimed to design a localized surface plasmonic resonance (LSPR)-based aptasensor for a circuit of cytosensing-PTT (COCP). This was achieved by coating a novel sandwich layer of polydopamine/gold nanoparticles/polydopamine (PDA/AuNPs/PDA) around the Ω-shaped fiber-optic (Ω-FO). The short-wavelength peak of the sandwich layer with strong resonance exhibited a high refractive index sensitivity (RIS). The modification with the T-shaped aptamer endowed FO-LSPR with unique characteristics of time-dependent sensitivity enhancement behavior for a sensitive cytosensor with the lowest limit of detection (LOD) of 13 cells/mL. The long-wavelength resonance peak in the sandwich layer appears in the near-infrared region. Hence, the rate of increased localized temperature of FO-LSPR was 160 and 30-fold higher than that of the bare and PDA-coated FO, indicating strong photothermal conversion efficiency. After considering the localized temperature distribution around the FO under the flow environment, the FO-LSPR-enabled aptasensor killed 77.6% of cancer cells in simulated blood circulation after five cycles of COCP. The FO-LSPR-enabled aptasensor improved the efficiency of the cytosensor and PTT to effectively kill cancer cells, showing significant potential for application in inhibiting cancer metastasis.

13.
Sci Rep ; 14(1): 15368, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965410

RESUMO

To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.


Assuntos
Próstata , Prostatite , Ondas Ultrassônicas , Humanos , Masculino , Prostatite/terapia , Prostatite/microbiologia , Prostatite/metabolismo , Próstata/microbiologia , Próstata/metabolismo , Próstata/patologia , Adulto , Bactérias/metabolismo , Bactérias/genética , Pessoa de Meia-Idade , Terapia por Ultrassom/métodos , Microbiota , RNA Ribossômico 16S/genética
14.
Adv Mater ; : e2406192, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-39003609

RESUMO

Bioelectricity provides electrostimulation to regulate cell/tissue behaviors and functions. In the human body, bioelectricity can be generated in electromechanically responsive tissues and organs, as well as biomolecular building blocks that exhibit piezoelectricity, with a phenomenon known as the piezoelectric effect. Inspired by natural bio-piezoelectric phenomenon, efforts have been devoted to exploiting high-performance synthetic piezoelectric biomaterials, including molecular materials, polymeric materials, ceramic materials, and composite materials. Notably, piezoelectric biomaterials polarize under mechanical strain and generate electrical potentials, which can be used to fabricate electronic devices. Herein, a review article is proposed to summarize the design and research progress of piezoelectric biomaterials and devices toward bionanotechnology. First, the functions of bioelectricity in regulating human electrophysiological activity from cellular to tissue level are introduced. Next, recent advances as well as structure-property relationship of various natural and synthetic piezoelectric biomaterials are provided in detail. In the following part, the applications of piezoelectric biomaterials in tissue engineering, drug delivery, biosensing, energy harvesting, and catalysis are systematically classified and discussed. Finally, the challenges and future prospects of piezoelectric biomaterials are presented. It is believed that this review will provide inspiration for the design and development of innovative piezoelectric biomaterials in the fields of biomedicine and nanotechnology.

15.
Health Sci Rep ; 7(7): e2251, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39015423

RESUMO

Background and Aims: The difficulty in treating chronic wounds due to the prolonged inflammation stage has affected a staggering 6.5 million people, accompanied by 25 billion USD annually in the United States alone. A 1.9% rise in chronic wound prevalence among Medicare beneficiaries was reported from 2014 to 2019. Besides, the global wound care market values were anticipated to increase from USD 20.18 billion in 2022 to USD 30.52 billion in 2030, suggesting an expected rise in chronic wounds financial burdens. The lack of feasibility in using traditional dry wound dressings sparks hydrogel development as an alternative approach to tackling chronic wounds. Since ancient times, honey has been used to treat wounds, including burns, and ongoing studies have also demonstrated its wound-healing capabilities on cellular and animal models. However, the fluidity and low mechanical strength in honey hydrogel necessitate the incorporation of other polymers. Therefore, this review aims to unravel the characteristics and feasibility of natural (chitosan and gelatin) and synthetic (polyvinyl alcohol and polyethylene glycol) polymers to be incorporated in the honey hydrogel. Methods: Relevant articles were identified from databases (PubMed, Google Scholar, and Science Direct) using keywords related to honey, hydrogel, and polymers. Relevant data from selected studies were synthesized narratively and reported following a structured narrative format. Results: The importance of honey's roles and mechanisms of action in wound dressings were discussed. Notable studies concerning honey hydrogels with diverse polymers were also included in this article to provide a better perspective on fabricating customized hydrogel wound dressings for various types of wounds in the future. Conclusion: Honey's incapability to stand alone in hydrogel requires the incorporation of natural and synthetic polymers into the hydrogel. With this review, it is hoped that the fabrication and commercialization of the desired honey composite hydrogel for wound treatment could be brought forth.

17.
Huan Jing Ke Xue ; 45(7): 4352-4360, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022979

RESUMO

Food waste is one of the important reservoirs of antibiotic resistance genes (ARGs), and its resource utilization has potential environmental risks. Anaerobic digestion (AD) technology can concurrently achieve resource recovery and ARGs removal, which is one of the popular resource technologies for food waste management. However, the removal efficiency of ARGs during the AD process is limited, and thus the safety of digestate for agricultural use is still questioned. Therefore, how to improve the performance of ARGs removal during the AD process is critical for efficient and environmentally friendly bioconversion of food waste. This study summarized the transmission pathways and mechanisms of ARGs in food waste; discussed the effects of different operation parameters on the transmission of ARGs in food waste during the AD process; described the research progress of exogenous addition of conductive materials, feedstock pretreatment, etc., strategies to enhance the removal of ARGs; and analyzed the migration regularity and removal mechanism of ARGs in food waste during the AD process, which mainly included microbial community structure evolution, mobile genetic element changes, and environmental factor changes. Finally, this study prospected the future improvement of methane yield and ARGs removal in the AD process of food waste based on the existing research.


Assuntos
Resistência Microbiana a Medicamentos , Anaerobiose , Resistência Microbiana a Medicamentos/genética , Eliminação de Resíduos/métodos , Reatores Biológicos/microbiologia , Alimentos , Biodegradação Ambiental , Perda e Desperdício de Alimentos
18.
Rev Cardiovasc Med ; 25(3): 80, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39076942

RESUMO

The residual SYNTAX score (rSS) is employed for the quantification of residual coronary lesions and to guide revascularization. rSS can be combined with other examinations to evaluate the severity of vascular disease and play an evaluative and guiding role in various scenarios. Furthermore, combining rSS with other indicators, benefits prognosis evaluation, and rSS-derived scores have been increasingly used in clinical practice. This article reviews the progress in the clinical application of rSS and its derived scores for complex coronary arteries and other aspects, based on relevant literature.

19.
Sci Rep ; 14(1): 17623, 2024 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085287

RESUMO

Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.


Assuntos
Administração Tópica , Dermatite Atópica , Dinitroclorobenzeno , Imunoglobulina E , Camundongos Endogâmicos BALB C , Pele , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Administração Oral , Masculino , Camundongos , Imunoglobulina E/sangue , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Modelos Animais de Doenças , Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Eosinófilos/efeitos dos fármacos , Interleucina-4/metabolismo , Mastócitos/efeitos dos fármacos
20.
J Cell Mol Med ; 28(14): e18555, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39075640

RESUMO

ARHGAP family genes are often used as glioma oncogenic factors, and their mechanism of action remains unexplained. Our research entailed a thorough examination of the immune microenvironment and enrichment pathways across various glioma subtypes. A distinctive 6-gene signature was developed employing the CGGA cohort, leading to insights into the disparities in clinical characteristics, mutation patterns, and immune cell infiltration among distinct risk categories. Additionally, a unique nomogram was established, grounded on ARHGAPs, with DCA curves illustrating the model's prospective clinical utility in guiding therapeutic strategies. Emphasizing the role of ARHGAP30, integral to our model, its impact on glioma severity and the credibility of our risk assessment model were substantiated through RT-qPCR, Western blot analysis, and cellular functional assays. We identified 6 ARHGAP family genes associated with glioma prognosis. Analysis using the Kaplan-Meier method indicated a correlation between elevated risk levels and adverse outcomes in glioma patients. The risk score, linked with tumour staging and IDH mutation status, emerged as an independent factor predicting prognosis. Patients in the high-risk category exhibited increased immune cell infiltration, enhanced tumour mutational burden, more pronounced expression of immune checkpoint genes, and a better response to ICB therapy. A nomogram, integrating the risk score with the pathological features of glioma patients, was developed. DCA analysis and cellular studies confirmed the model's potential to improve clinical treatment outcomes for patients. A novel ARHGAP family gene signature reveals the prognosis of glioma.


Assuntos
Neoplasias Encefálicas , Proteínas Ativadoras de GTPase , Regulação Neoplásica da Expressão Gênica , Glioma , Nomogramas , Humanos , Glioma/genética , Glioma/patologia , Glioma/mortalidade , Proteínas Ativadoras de GTPase/genética , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Biomarcadores Tumorais/genética , Feminino , Mutação/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Masculino , Perfilação da Expressão Gênica , Transcriptoma , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade
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