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1.
Soft Matter ; 20(16): 3436-3447, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38564251

RESUMO

Flexible actuation materials play a crucial role in biomimetic robots. Seeking methods to enhance actuation and functionality is one of the directions in which actuators strive to meet the high-performance and diverse requirements of environmental conditions. Herein, by utilizing the method of adsorbing N-doped carbon dots (NCDs) onto SiO2 to form clusters of functional particles, a NCDs@SiO2/PDMS elastomer was prepared and its combined optical and electrical co-stimulation properties were effectively harnessed to develop a biomimetic crawling robot resembling Rhagophthalmus (firefly). The introduction of NCDs@SiO2 cluster particles not only effectively improves the mechanical and dielectric properties of the elastomer but also exhibits fluorescence response and actuation response under the co-stimulation of UV and electricity, respectively. Additionally, a hybrid dielectric elastomer actuator (DEA) with a transparent SWCNT mesh electrode exhibits two notable advancements: an 826% increase in out-of-plane displacement under low electric field stimulation compared to the pure matrix and the ability of NCDs to maintain a stable excited state within the polymer for an extended duration under UV-excitation. Simultaneously, the transparent biomimetic crawling robot can stealthily move in specific environments and fluoresce under UV light.

4.
Biochem Biophys Res Commun ; 703: 149686, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38367513

RESUMO

Transforming growth factor ß1 (TGFB1) refers to a pleiotropic cytokine exerting contrasting roles in hematopoietic stem cells (HSCs) functions in vitro and in vivo. However, the understanding of hematopoiesis in vivo, when TGFB1 is constantly deactivated, is still unclear, mainly due to significant embryonic lethality and the emergence of a fatal inflammatory condition, which makes doing these investigations challenging. Our study aims to find the specific role of TGFB1 in regulating hematopoiesis in vivo. We engineered mice strains (Vav1 or Mx1 promoter-driven TGFB1 knockout) with conditional knockout of TGFB1 to study its role in hematopoiesis in vivo. In fetal and adult hematopoiesis, TGFB1 KO mice displayed deficiency and decreased self-renewal capacity of HSCs with myeloid-biased differentiation. The results were different from the regulating role of TGFB1 in vitro. Additionally, our results showed that TGFB1 deficiency from fetal hematopoiesis stage caused more severe defect of HSCs than in the adult stage. Mechanistically, our findings identified TGFB1-SOX9-FOS/JUNB/TWIST1 signal axis as an essential regulating pathway in HSCs homeostasis. Our study may provide a scientific basis for clinical HSC transplantation and expansion.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas , Fator de Crescimento Transformador beta1 , Animais , Camundongos , Diferenciação Celular , Citocinas/metabolismo , Hematopoese/genética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Fator de Crescimento Transformador beta1/metabolismo
5.
Heliyon ; 10(4): e25568, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420407

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a highly heterogeneous cancer. This heterogeneity has an impact on the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been found to play regulatory functions in cancer immunity. However, the global landscape of immune-derived lncRNA signatures has not yet been explored in colorectal cancer. METHODS: In this study, we applied DESeq2 to identify differentially expressed lncRNAs in colon cancer. Next, we performed an integrative analysis to globally identify immune-driven lncRNA markers in CRC, including immune-associated pathways, tumor immunogenomic features, tumor-infiltrating immune cells, immune checkpoints, microsatellite instability (MSI) and tumor mutation burden (TMB). RESULTS: We also identified dysregulated lncRNAs, such as LINC01354 and LINC02257, and their clinical relevance in CRC. Our findings revealed that the differentially expressed lncRNAs were closely associated with immune pathways. In addition, we found that RP11-354P11.3 and RP11-545G3.1 had the highest association with the immunogenomic signature. As a result, these signatures could serve as markers to assess immunogenomic activity in CRC. Among the immune cells, resting mast cells and M0 macrophages had the highest association with lncRNAs in CRC. The AC006129.2 gene was significantly associated with several immune checkpoints, for example, programmed cell death protein 1 (PD-1) and B and T lymphocyte attenuator (BTLA). Therefore, the AC006129.2 gene could be targeted to regulate the condition of immune cells or immune checkpoints to enhance the efficacy of immunotherapy in CRC patients. Finally, we identified 15 immune-related lncRNA-generated open reading frames (ORFs) corresponding to 15 cancer immune epitopes. CONCLUSION: In conclusion, we provided a genome-wide immune-driven lncRNA signature for CRC that might provide new insights into clinical applications and immunotherapy.

6.
Int J Biol Macromol ; 260(Pt 1): 129432, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228208

RESUMO

Growing evidence confirms associations between glycogen metabolic re-wiring and the development of liver cancer. Previous studies showed that glycogen structure changes abnormally in liver diseases such as cystic fibrosis, diabetes, etc. However, few studies focus on glycogen molecular structural characteristics during liver cancer development, which is worthy of further exploration. In this study, a rat model with carcinogenic liver injury induced by diethylnitrosamine (DEN) was successfully constructed, and hepatic glycogen structure was characterized. Compared with glycogen structure in the healthy rat liver, glycogen chain length distribution (CLD) shifts towards a short region. In contrast, glycogen particles were mainly present in small-sized ß particles in DEN-damaged carcinogenic rat liver. Comparative transcriptomic analysis revealed significant expression changes of genes and pathways involved in carcinogenic liver injury. A combination of transcriptomic analysis, RT-qPCR, and western blot showed that the two genes, Gsy1 encoding glycogen synthase and Gbe1 encoding glycogen branching enzyme, were significantly altered and might be responsible for the structural abnormality of hepatic glycogen in carcinogenic liver injury. Taken together, this study confirmed that carcinogenic liver injury led to structural abnormality of hepatic glycogen, which provided clues to the future development of novel drug targets for potential therapeutics of carcinogenic liver injury.


Assuntos
Carcinógenos , Neoplasias Hepáticas , Ratos , Animais , Carcinógenos/toxicidade , Dietilnitrosamina/toxicidade , Glicogênio Hepático/efeitos adversos , Fígado , Glicogênio , Carcinogênese
7.
Int J Biol Macromol ; 260(Pt 1): 129332, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232867

RESUMO

Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of ß-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/ß-catenin signaling pathway. Stimulation with the Wnt/ß-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/ß-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.


Assuntos
Glioma , Via de Sinalização Wnt , Humanos , Via de Sinalização Wnt/genética , Glioma/patologia , beta Catenina/genética , beta Catenina/metabolismo , Proliferação de Células , Fenótipo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
8.
J Multidiscip Healthc ; 17: 83-91, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38205125

RESUMO

Objective: The primary aim of this study was to examine the extent of nutritional awareness concerning dietary requisites within a cohort comprising pediatric recipients of liver and kidney transplants, along with their respective caregivers. The overarching goal was to establish a foundation for enhancing the dietary nutrition of this specific population. Methods: This was a qualitative research study, involving in-depth interviews and subsequent qualitative data analysis. Our sample included pediatric patients in a specific age range who had undergone a liver or kidney transplant, as well as their parents. The data analysis technique we used was content analysis. Results: The survey focused on knowledge of dietary requirements and restrictions, nutritional needs, and adherence to daily dietary requirements among pediatric patients and their respective caregivers. Approximately 30% of the parents lacked relevant nutritional awareness, 30% relied on a single source for acquiring nutritional knowledge, and 40% expressed a considerable need for nutritional guidance. Our findings revealed a deficiency in the understanding of nutritional and dietary requirements for children who have undergone a liver or kidney transplant. Their nutrient intake was unbalanced, and their dietary habits were irregular, highlighting the need for better nutritional guidance and monitoring. Conclusion: The nutritional awareness and knowledge of dietary requirements among pediatric liver and kidney transplant recipients and their care providers are inadequate. Medical professionals are urged to tackle this concern by imparting comprehensive education to parents regarding the nutritional prerequisites essential for their children post-transplant. This approach empowers parents to implement requisite dietary modifications effectively. Furthermore, healthcare institutions should augment the nutritional proficiency of their medical staff through meticulously structured training initiatives.

9.
Heliyon ; 10(1): e23596, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38205334

RESUMO

Due to their geometry and thermal physiology, hands are most vulnerable to cold weather injuries and loss of dexterity. Gloves are the most common for hand protection during exposure to extreme thermal and hazardous environments. Although glove microclimate properties such as area factor, air gap thickness, and contact area play a significant role in thermal protection, identifying local (at individual hand segments) glove microclimate properties is still a research gap. For the first time, the glove-microclimate properties for 16 hand segments at high spatial resolution were analyzed by employing state-of-the-art hand-held 3D scanner and post-processing techniques for different glove types. Our results clearly indicate that the glove area factor for distal phalanges is significantly higher (by 49.8 %) than that for other hand segments, which increases the heat transfer from distal phalanges. In contrast, average air gap thickness was relatively uniform across all hand segments. The glove type had a pronounced effect on glove microclimate properties, e.g., bulky and heavy cold weather protective gloves had a larger average air gap thickness and glove area factor. Regression models are also developed to estimate the glove microclimate properties from simple measurement (i.e., ease allowance). Overall, this study provides essential information for the design and development of protective gloves that can help improve safety, comfort, and dexterity. Methods and mathematical models developed in this study also contribute to facilitating extremity (e.g., hand) focused thermoregulation modeling, hazard simulation, injury prediction, ergonomic design, optimum performance (dexterity and tactility) along with thermal protection.

10.
Mol Neurobiol ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193984

RESUMO

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.

11.
Org Biomol Chem ; 22(5): 998-1009, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38186088

RESUMO

An efficient Ru(II)-catalyzed C-H activation-based spiroannulation of benzoxazines with the easily available benzoquinone and N-sulfonyl quinone monoimine has been realized, providing a straightforward strategy to access NH-containing spiropyrans in moderate to good yields with good functional group compatibility. The procedure features atom- and step-economy, mild conditions, and excellent chemoselectivity. Moreover, a catalytically competent five-membered cycloruthenated complex has been isolated.

12.
J Chemother ; : 1-15, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38291982

RESUMO

With the development of newer biomarkers in the diagnosis of gastric cancer (GC), therapeutic targets are emerging and molecular-targeted therapy is in progress RNA interference has emerged as a promising method of gene targeting therapy. However, naked small interfering RNA (siRNA) is unstable and susceptible to degradation, so employing vectors for siRNA delivery is the focus of our research. Therefore, we developed LMWP modified PEG-SS-PEI to deliver siRNA targeting BRD4 (L-NPs/siBRD4) for GC therapy. L-NPs/siBRD4 were prepared by electrostatic interaction and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release characteristics, cellular uptake and intracellular localization were also investigated. The in vitro anticancer activity of the prepared nanoparticles was analysed by MTT, Transwell invasion and wound healing assay. Quantitative real time-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of gene silencing. The results showed that the optimal N/P was 30 and the prepared L-NPs/siBRD4 uniformly distributed in the system with a spherical and regular shape. L-NPs/siBRD4 exhibited an accelerated release in GSH-containing media from 12h to 24h. The uptake of L-NPs/siBRD4 was enhanced and mainly co-localized in the lysosomes. After 6h incubation, LMWP modified PEG-SS-PEI helped siRNA escape from the lysosomes and diffused into the cytoplasm. L-NPs/siBRD4 significantly inhibited the proliferation, migration and invasion of cells. This might be related with the silence of BRD4, then inhibition of PI3K/Akt and c-Myc. Our results demonstrate that L-NPs/siBRD4 are a novel delivery system with anticancer, which may provide a more effective strategy for GC treatment.

13.
Curr Cancer Drug Targets ; 24(2): 167-177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37282642

RESUMO

BACKGROUND: BRD4 is a member of the bromodomain and extra terminal domain (BET) family of proteins, containing two bromodomains and one extra terminal domain, and is overexpressed in several human malignancies. However, its expression in gastric cancer has not yet been well illustrated. OBJECTIVE: This study aimed to elucidate the overexpression of BRD4 in gastric cancer and its clinical significance as a novel therapeutic target. METHODS: Fresh gastric cancer tissues and paraffin-embedded specimens of gastric cancer patients were collected, and the BRD4 expression was examined by Western Blot Analysis (WB) and Immunohistochemistry Analysis (IHC), respectively. The possible relationship between BRD4 expression and the clinicopathological features as well as survival in gastric cancer patients was analyzed. The effect of BRD4 silencing on human gastric cancer cell lines was investigated by MTT assay, WB, wound healing assay, and Transwell invasion. RESULTS: The results showed that the expression level in tumor tissues and adjacent tissues was significantly higher than that in normal tissues, respectively (P < 0.01). BRD4 expression level in gastric cancer tissues was strongly correlated with the degree of tumor differentiated degree (P = 0.033), regional lymph nodes metastasis (P = 0.038), clinical staging (P = 0.002), and survival situation (P = 0.000), while the gender (P = 0.564), age (P = 0.926) and infiltrating depth (P = 0.619) of patients were not associated. Increased BRD4 expression resulted in poor overall survival (P = 0.003). In in vitro assays, BRD4 small interfering RNA resulted in significantly decreased BRD4 protein expression, therefore inhibiting proliferation, migration, and invasion of gastric cancer cells. CONCLUSION: BRD4 might be a novel biomarker for the early diagnosis, prognosis, and therapeutic target in gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Relevância Clínica , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
14.
Int J Biol Macromol ; 256(Pt 1): 128405, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016609

RESUMO

The O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is a critical post-translational modification and closely linked to various physiological and pathological conditions. The O-GlcNAc transferase (OGT) functions as the only glycosyltransferase of O-GlcNAc glycosylation by transferring GlcNAc from UDP-GlcNAc to serine or threonine residues on protein substrates. The interaction mode of UDP-GlcNAc against OGT has been preliminarily revealed by the crystal structures, yet an atomic-level comprehension for the conformational dynamics of the recognition process remains elusive. Here, we construct the Markov state model based on extensive all-atom molecular dynamics (MD) simulations with an aggregated simulation time of ∼9 µs, and reveal that the UDP-GlcNAc recognition process by OGT encompasses four key metastable states, occurring within an estimated timescale of ∼10 µs. During UDP-GlcNAc recognition process, we find the pyrophosphate moiety (P2O52-) initially anchors to the active pocket via salt bridge and hydrogen bonds, facilitating subsequent binding of the uridine and GlcNAc moieties. Furthermore, the functional roles of K842 involved in the salt bridge with P2O52- were evaluated through extra mutant MD simulations. Overall, our study provides valuable insights into the UDP-GlcNAc recognition mechanism by OGT, which could further aid in mechanistic studies of O-GlcNAc glycosylation and drug development targeting on OGT.


Assuntos
Simulação de Dinâmica Molecular , N-Acetilglucosaminiltransferases , Processamento de Proteína Pós-Traducional , Glicosilação , Difosfato de Uridina/metabolismo , Acetilglucosamina/metabolismo
15.
Hematol Oncol ; 42(1): e3224, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712442

RESUMO

Myelodysplastic syndromes (MDS) patients often experience CD8+ T lymphocytes exhaustion, which plays a crucial role in the development of MDS. However, the specific role of thymocyte selection-associated high mobility box protein (TOX) in the CD8+ T lymphocytes exhaustion in MDS patients remains unclear. In this study, we investigated the role of TOX in CD8+ T lymphocytes exhaustion in patients with MDS. The expression of TOX, inhibitory receptors (IRs), and functional molecules in peripheral blood T lymphocytes of MDS patients and normal controls were detected using flow cytometry. Lentiviral transduction was used to create stable TOX-knockdown CD8+ T lymphocytes, and small interfering RNA (si-RNA) was used to knock down TOX in Jurkat cells. The expression of TOX was found to be significantly higher in CD8+ T lymphocytes of MDS patients compared to normal controls. This was associated with upregulated IRs and reduced expression of functional molecules such as Granzyme and Perforin. Myelodysplastic syndromes patients with higher TOX expression had poor clinical indicators and shorter survival. Knockdown of TOX using sh-RNA partially reverses the exhausted phenotype and enhances the lethality of CD8+ T lymphocytes. Moreover, the knockdown of TOX using si-RNA in Jurkat cells improved cell proliferation activity, down-regulated IRs and activated PI3K/AKT/mTOR signaling pathway. TOX promotes the exhaustion of CD8+ T lymphocytes by inhibiting PI3K/AKT/mTOR pathway, and targeted inhibition of TOX could partially restore the effector functions and activity of CD8+ T lymphocytes.


Assuntos
Síndromes Mielodisplásicas , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Timócitos/metabolismo , Serina-Treonina Quinases TOR , RNA/metabolismo
16.
Naunyn Schmiedebergs Arch Pharmacol ; 397(3): 1327-1346, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37695335

RESUMO

Recently, various studies have been devoted to the study of transient receptor potential vanilloid member 1 (TRPV1)-related diseases, potential drugs, and related mechanisms. The objective of this investigation was to examine the significant areas and cutting-edge developments in TRPV1 study within recent decades. Articles or reviews were obtained from the Web of Science Core Collection. VOSviewer 1.6.18 and CiteSpace 6.1 R2 software were utilized to examine publication growth, distribution by country/region, institution, journal, authorship, references, and keywords. The software identified keywords with a high citation burstiness to determine emerging topics. From 1990 to 2023, the annual global publications increased by 62,000%, from 1 to 621. Journal of neuroscience published the most manuscripts and Nature produced the highest citations. The USA, Seoul National University and Di marzo V were the most productive and impactful institution, country, and author, respectively. "TRPV1," "Capsaicin receptor," "Activation," and "Pain" are the most important keywords. The burst keywords "TRPV1 channel," "Oxidative stress," "TRPV1 structure," and "Cancer" are supposed to be the research frontiers. The present study offers valuable insights into the understanding of TRPV1 and pain-related conditions. The research on TRPV1 has demonstrated a steady increase in studies related to pain-related diseases in the past few decades. The significance of TRPV1 in cancer pathogenesis and the resolution of its structure will emerge as a new academic trend in this field, providing direction for more widespread and comprehensive studies in the future.


Assuntos
Antineoplásicos , Humanos , Bibliometria , Autoria , Estresse Oxidativo , Dor
17.
Redox Biol ; 69: 103016, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160539

RESUMO

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.


Assuntos
Exossomos , Miocardite , RNA Longo não Codificante , Viroses , Animais , Humanos , Camundongos , Exossomos/metabolismo , Macrófagos/metabolismo , 60645 , Miocardite/metabolismo , RNA Longo não Codificante/genética
18.
Front Behav Neurosci ; 17: 1271653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074521

RESUMO

Maternal exposure to inflammation may represent a major risk factor for neuropsychiatric disorders with associated cognitive dysfunction in offspring in later life. Growing evidence has suggested that resveratrol exerts a beneficial effect on cognitive impairment via its anti-inflammatory and antioxidant properties and by ameliorating synaptic dysfunction. However, how resveratrol affects maternal immune activation-induced cognitive dysfunction and the underlying mechanisms are unclear. In the present study, pregnant dams were given an intraperitoneal injection of lipopolysaccharide (LPS; 50 µg/kg) on gestational day 15. Subsequently, the offspring mice were treated or not with resveratrol (40 mg/kg) from postnatal day (PND) 60 to PND 88. Male offspring were selected for the evaluation of cognitive function using the Morris water maze test. The hippocampal levels of pro-inflammatory cytokines were examined by ELISA. The mRNA and protein levels of sirtuin-1 (SIRT1), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYP) were determined by RT-qPCR and western blot, respectively. The results showed that male offspring mice exposed to LPS in utero exhibited learning and memory impairment. Additionally, the levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) were increased while those of SIRT1, BDNF, PSD-95, and SYP were decreased in male offspring of LPS-treated mothers. Treatment with resveratrol reversed cognitive impairment and attenuated the increase in the levels of pro-inflammatory cytokines induced by maternal immune activation in the offspring mice. Furthermore, resveratrol reversed the deleterious effects of maternal immune activation on SIRT1, BDNF, PSD-95, and SYP levels in the hippocampus. Collectively, our results suggested that resveratrol can effectively improve learning and memory impairment induced by maternal immune activation via the modulation of inflammation and synaptic dysfunction.

19.
Foods ; 12(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38137308

RESUMO

This study involved the extraction of polysaccharides from jujube for application in apricot storage. Although near-freezing temperature (NFT) storage is commonly employed for preserving fresh fruit, its effectiveness is somewhat limited. Incorporating jujube polysaccharides was proposed to augment the preservative effect on apricots. Our findings demonstrated that the combined use of NFT and jujube polysaccharides can maintain fruit color, and effectively inhibit decay. Additionally, Tandem Mass Tag (TMT) quantitative proteomic technology was utilized to analyze protein variations in 'Diaogan' apricots during storage. This dual approach not only markedly lowered the activity of polyphenol cell wall-degrading enzymes (p < 0.05) but also revealed 1054 differentially expressed proteins (DEPs), which are related to sugar and energy metabolism, stress response and defense, lipid metabolism, and cell wall degradation. The changes in DEPs indicated that the combined use of NFT and jujube polysaccharides could accelerate the conversion of malic acid to oxaloacetic acid and regulate antioxidant ability, potentially extending the storage lifespan of apricot fruit.

20.
Braz J Med Biol Res ; 56: e13013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970924

RESUMO

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Heparina/efeitos adversos , Estudos Retrospectivos , Antitrombinas/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , População do Leste Asiático , Resultado do Tratamento , Hirudinas/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Fragmentos de Peptídeos/efeitos adversos , Fibrinolíticos , Proteínas Recombinantes/efeitos adversos
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