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1.
Anim Nutr ; 17: 49-60, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558755

RESUMO

The use of hemp as a forage source in livestock diets has been less studied because bioactive residues in animal tissues may pose a risk to consumers. This study investigated the effects of partial substitution of alfalfa hay (AH) with hemp forage (HF) in growing goat diets on growth performance, carcass traits, ruminal fermentation characteristics, rumen microbial communities, blood biochemistry, and antioxidant indices. Forty Xiangdong black goats with body weight (BW) 7.82 ± 0.57 kg (mean ± SD) were grouped by BW and randomly assigned into one of the four treatment diets (n = 10/treatment) in a completely randomized design. The goats were fed ad libitum total mixed rations containing 60% forage and 40% concentrate (DM basis). The diets included control (CON; 60% AH and 40% concentrate), 55% AH and 5% HF (HF5), 50% AH and 10% HF (HF10), and 40% AH and 20% HF (HF20). Increasing the substitution of HF for AH linearly decreased (P < 0.01) DM intake and improved feed conversion efficiency. However, final BW, average daily gain, carcass traits, meat quality, and most blood biochemistry indices did not differ among treatments. The ruminal NH3-N concentration and blood urine nitrogen linearly increased (P < 0.01) with increasing substitution rate of HF, whereas the total volatile fatty acids concentration quadratically changed (P < 0.01). Substitution of AH with HF had no effect on the diversity and richness of ruminal microbes, though it linearly decreased (P = 0.040) Prevotella_1 and linearly increased (P = 0.017) Rikenellaceae_RC9_gut_group. The cannabinoids and/or their metabolites were detected in both ruminal filtrates (8) and plasma (4), however, no detectable cannabinoid-related residues were observed in meat. These results indicate that the HF could be used to partially substitute AH in goat diets, whereas the effects vary between substitution rates of HF for AH. Although no cannabinoid-related residues were detected in meat, the presence of cannabinoids residues in blood warrants further study of HF feeding to confirm the cannabinoids residues are not present in the animal products.

2.
J Phys Chem B ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568211

RESUMO

Using nanobubbles as geometrical confinements, we create a thin water film (∼10 nm) in a graphene liquid cell and investigate the evolution of its instability at the nanoscale under transmission electron microscopy. The breakdown of the water films, resulting in the subsequent formation and growth of nanodroplets, is visualized and generalized into different modes. We identified distinct droplet formation and growth modes by analyzing the dynamic processes involving 61 droplets and 110 liquid bridges within 31 Graphene Liquid Cells (GLCs). Droplet formation is influenced by their positions in GLCs, taking on a semicircular shape at the edge and a circular shape in the middle. Growth modes include liquid mass transfer driven by Plateau-Rayleigh instability and merging processes in and out-of-plane of the graphene interface. Droplet growth can lead to the formation of liquid bridges for which we obtain multiview projections. Data analysis reveals the general dynamics of liquid bridges, including drawing liquids from neighboring residual water films, merging with surrounding droplets, and merging with other liquid bridges. Our experimental observations provide insights into fluid transport at the nanoscale.

3.
Int Immunopharmacol ; 130: 111772, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38432148

RESUMO

Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factorkappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.


Assuntos
Benzoatos , NF-kappa B , Complicações Cognitivas Pós-Operatórias , Receptor alfa de Ácido Retinoico , Tetra-Hidronaftalenos , Animais , Camundongos , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos Endogâmicos ICR , Fator 88 de Diferenciação Mieloide/metabolismo , Doenças Neuroinflamatórias/prevenção & controle , NF-kappa B/metabolismo , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Receptor alfa de Ácido Retinoico/agonistas , Transdução de Sinais , Tetra-Hidronaftalenos/farmacologia , Tetra-Hidronaftalenos/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Tretinoína/farmacologia
4.
iScience ; 27(3): 109270, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38487014

RESUMO

Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk of GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) are essential mediators during tumor immune-microenvironment remodeling initiated by GSCs, resulting in M2 polarization of tumor-associated macrophages (TAMs) as we reported previously. Our data disclosed aberrant upregulation of miR-374b-3p in both clinical glioblastoma specimens and human cell lines of GSCs. MiR-374b-3p level was high in GSCs-exos and can be internalized by macrophages. Mechanistically, GSCs exosomal miR-374b-3p induced M2 polarization of macrophages by downregulating phosphatase and tensin expression, thereby promoting migration and tube formation of vascular endothelial cells after coculture with M2 macrophages. Cumulatively, these data indicated that GSCs exosomal miR-374b-3p can enhance tumor angiogenesis by inducing M2 polarization of macrophages, as well as promote malignant progression of glioblastoma. Targeting exosomal miR-374b-3p may serve as a potential target against glioblastoma.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38501698

RESUMO

Background: Sepsis is a complex clinical syndrome caused by a dysregulated host immune response to infection. This study aimed to identify a competing endogenous RNA (ceRNA) network that can greatly contribute to understanding the pathophysiological process of sepsis and determining sepsis biomarkers. Methods: The GSE100159, GSE65682, GSE167363, and GSE94717 datasets were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene coexpression network analysis was performed to find modules possibly involved in sepsis. A long noncoding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) network was constructed based on the findings. Single-cell analysis was performed. Human umbilical vein endothelial cells were treated with lipopolysaccharide (LPS) to create an in vitro model of sepsis for network verification. Reverse transcription-polymerase chain reaction, fluorescence in situ hybridization, and luciferase reporter genes were used to verify the bioinformatic analysis. Result: By integrating data from three GEO datasets, we successfully constructed a ceRNA network containing 18 lncRNAs, 7 miRNAs, and 94 mRNAs based on the ceRNA hypothesis. The lncRNA ZFAS1 was found to be highly expressed in LPS-stimulated endothelial cells and may thus play a role in endothelial cell injury. Univariate and multivariate Cox analyses showed that only SLC26A6 was an independent predictor of prognosis in sepsis. Overall, our findings indicated that the ZFAS1/hsa-miR-449c-5p/SLC26A6 ceRNA regulatory axis may play a role in the progression of sepsis. Conclusion: The sepsis ceRNA network, especially the ZFAS1/hsa-miR-449c-5p/SLC26A6 regulatory axis, is expected to reveal potential biomarkers and therapeutic targets for sepsis management.

6.
CNS Neurosci Ther ; 30(2): e14599, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332576

RESUMO

BACKGROUND: Glioblastoma is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against glioblastoma. Nevertheless, the therapeutic efficacy of TMZ appears to be remarkably limited, because of low cytotoxic efficiency against glioblastoma. Besides, various mechanical studies and the corresponding strategies fail to enhancing TMZ curative effect in clinical practice. Our previous studies have disclosed remodeling of glial cells by GSCs, but the roles of these transformed cells on promoting TMZ resistance have never been explored. METHODS: Exosomes were extracted from GSCs culture through standard centrifugation procedures, which can activate transformation of normal human astrocytes (NHAs) totumor-associated astrocytes (TAAs) for 3 days through detect the level of TGF-ß, CD44 and tenascin-C. The secretive protein level of ALKBH7 of TAAs was determined by ELISA kit. The protein level of APNG and ALKBH7 of GBM cells were determined by Western blot. Cell-based assays of ALKBH7 and APNG triggered drug resistance were performed through flow cytometric assay, Western blotting and colony formation assay respectively. A xenograft tumor model was applied to investigate the function of ALKBH7 in vivo. Finally, the effect of the ALKBH7/APNG signaling on TMZ resistance were evaluated by functional experiments. RESULTS: Exosomes derived from GSCs can activate transformation of normal human astrocytes (NHAs)to tumor-associated astrocytes (TAAs), as well as up-regulation of ALKBH7expression in TAAs. Besides, TAAs derived ALKBH7 can regulate APNG gene expression of GBM cells. After co-culturing with TAAs for 5 days, ALKBH7 and APNG expression in GBM cells were elevated. Furthermore, Knocking-down of APNG increased the inhibitory effect of TMZ on GBM cells survival. CONCLUSION: The present study illustrated a new mechanism of glioblastoma resistance to TMZ, which based on GSCs-exo educated TAAs delivering ALKBH7 to enhance APNG expression of GBM cells, which implied that targeting on ALKBH7/APNG regulation network may provide a new strategy of enhancing TMZ therapeutic effects against glioblastoma.


Assuntos
Neoplasias Encefálicas , Exossomos , Glioblastoma , Adulto , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioblastoma/patologia , Astrócitos/metabolismo , Exossomos/metabolismo , Células-Tronco/metabolismo , Neoplasias Encefálicas/genética , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Enzimas AlkB , Proteínas Mitocondriais
7.
Cell Tissue Res ; 395(3): 285-297, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38353742

RESUMO

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.


Assuntos
Hipogonadismo , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Apoptose , Proliferação de Células/genética , Peróxido de Hidrogênio , Hipogonadismo/genética , Hibridização in Situ Fluorescente , Células Intersticiais do Testículo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/metabolismo , Sirtuína 1/genética , Testosterona/farmacologia
8.
Phytochemistry ; 220: 114033, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373572

RESUMO

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A-F (1-6) and hemslyencosides A-D (7-10), together with twenty previously reported compounds (11-30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 µM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.


Assuntos
Antineoplásicos , Triterpenos , Humanos , Triterpenos/farmacologia , Triterpenos/química , Glicosídeos/química , Tubérculos/química , Células HeLa , Estrutura Molecular
9.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345210

RESUMO

The suture technique for a ruptured annulus fibrosus (AF) under full-endoscopy remains challenging. Direct suturing of a ruptured annular tear after full decompression has been shown to decrease the recurrence rate of lumbar disc herniation during endoscopic surgery. Traditional suture operations under endoscopy involve only simple suturing of the ruptured AF. Due to the weak and poor quality of the AF tissue around the tear portal, using this area as needle insertion points during suturing may lead to insufficient tension and a low success rate of AF closure. Currently, there is no detailed technical illustration based on video for AF tear suturing under lumbar full-endoscopy. We innovatively propose a method of covering and suturing the AF tear by pulling up the posterior longitudinal ligament (PLL) under lumbar endoscopy and using three stitches (PLL-AF suture technique). The patient who received the novel suture technique achieved satisfactory results. Six months after the operation, lumbar MRI showed no evidence of recurrence in the outpatient clinic.


Assuntos
Anel Fibroso , Lacerações , Humanos , Resultado do Tratamento , Vértebras Lombares/cirurgia , Endoscopia/métodos , Discotomia/métodos , Lacerações/cirurgia , Técnicas de Sutura , Descompressão , Estudos Retrospectivos
10.
Cell Death Discov ; 10(1): 71, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341418

RESUMO

Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

11.
Photodiagnosis Photodyn Ther ; 45: 103984, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244654

RESUMO

Rejection is the primary factor affecting the functionality of a kidney post-transplant, where its prompt prediction of risk significantly influences therapeutic strategies and clinical outcomes. Current graft health assessment methods, including serum creatinine measurements and transplant kidney puncture biopsies, possess considerable limitations. In contrast, urine serves as a direct indicator of the graft's degenerative stage and provides a more accurate measure than peripheral blood analysis, given its non-invasive collection of kidney-specific metabolite. This research entailed collecting fluorescent fingerprint data from 120 urine samples of post-renal transplant patients using hyperspectral imaging, followed by the development of a learning model to detect various forms of immunological rejection. The model successfully identified multiple rejection types with an average diagnostic accuracy of 95.56 %.Beyond proposing an innovative approach for predicting the risk of complications post-kidney transplantation, this study heralds the potential introduction of a non-invasive, rapid, and accurate supplementary method for risk assessment in clinical practice.


Assuntos
Transplante de Rim , Fotoquimioterapia , Humanos , Transplante de Rim/efeitos adversos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Corantes , Imageamento Hiperespectral , Complicações Pós-Operatórias
13.
Glia ; 72(5): 857-871, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38234042

RESUMO

Tumor-associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC-derived exosomes (GSC-EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC-EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA-related markers (TGF-ß, CD44, and tenascin-C) were observed in the TAAs. Furthermore, GSC-derived exosomal miR-3065-5p could be delivered to NHAs, and miR-3065-5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR-3065-5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA-related markers. In addition, both GSC-EXO-induced and miR-3065-5p-overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR-3065-5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC-EXOs induce the transformation of NHAs into TAAs via the miR-3065-5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in-depth mechanistic studies are still needed.


Assuntos
Exossomos , Glioblastoma , Glioma , MicroRNAs , Humanos , Glioblastoma/patologia , Astrócitos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/metabolismo , Glioma/patologia , Temozolomida/farmacologia , Temozolomida/metabolismo , Células-Tronco Neoplásicas/metabolismo , Carcinogênese/genética , Proliferação de Células , Microambiente Tumoral , Proteínas Supressoras de Tumor/metabolismo , Guanilato Quinases/metabolismo
14.
Environ Sci Pollut Res Int ; 31(6): 9565-9581, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38191738

RESUMO

Yangcheng Lake, a typical fishery lake in the middle and lower reaches of the Yangtze River, is threatened by eutrophication. As the main performers of biogeochemical cycles, microorganisms affect the ecological stability of the lake. To study the structural characteristics of the microbial community in Yangcheng Lake and rivers entering Yangcheng Lake and the response relationship with environmental factors, the microbial community was categorized based on the contour of Yangcheng Lake, the major rivers entering Yangcheng Lake, and the pollution sources. The distribution characteristics of seven physicochemical indices were analyzed, including total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), water temperature (WT), pH, dissolved oxygen (DO), and ratio of total nitrogen to total phosphorus (TN/TP). Characterization of microbial community structure based on 16S rRNA high-flux sequencing technology and ANOSIM analysis were used to explore the differences in the relative abundance of microorganisms at each sampling point in the lake and rivers, and redundancy analysis (RDA) was used to analyze the relationship between the microbial community and physicochemical factors. The results showed that the dominant phyla, genera of microorganisms, and the total number of OTUs in the lake and rivers were similar. The dominant phyla included Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, and Verrucomicrobia; the dominant genera included the hgcI clade, CL500-29 marine group, Microcystis PCC-7914, Chloroplast_norank, Clade III_norank, and Flavobacterium. ANOSIM analyses revealed that the microbial community of Yangcheng Lake exhibited an association with geographical space, while the microbial community in the rivers that was linked to the type of pollution source. Redundancy analysis (RDA) indicated that dissolved oxygen (DO), total nitrogen (TN), and pH were significantly correlated with the dominant phyla in Yangcheng Lake (p < 0.05), while total nitrogen (TN), water temperature(WT), and the ratio of total nitrogen to total phosphorus (TN/TP) were significantly related with the dominant genera in Yangcheng Lake (p < 0.05). Total nitrogen (TN) was also significantly linked to the dominant phyla and genera of the tributaries (p < 0.05). Despite the structural similarities in microbial communities between Yangcheng Lake and its inflowing rivers, environmental factors demonstrated significant associations with these communities, providing crucial data support for pollution prevention and the ecological restoration of Yangcheng Lake.


Assuntos
Cianobactérias , Microbiota , Lagos/química , Rios/química , Monitoramento Ambiental , Estações do Ano , RNA Ribossômico 16S , Nitrogênio/análise , Fósforo/análise , Água/análise , Oxigênio/análise , China
15.
J Diabetes ; 16(1): e13470, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37700547

RESUMO

AIM: Both the activation of glycogen synthase kinase-3ß (GSK-3ß) and the presence of ApoE ε4 genotype have been found to respectively correlate with cognitive decline in patients with type 2 diabetes mellitus (T2DM), who further show a high incidence of developing Alzheimer's disease. However, the relationship between ApoE ε4 and GSK-3ß in the cognitive impairment of T2DM patients remains unclear. METHODS: ApoE genotypes and platelet GSK-3ß level were measured in 1139 T2DM patients recruited from five medical centers in Wuhan, China. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). The association and the relationships among apolipoprotein E (ApoE) genotypes, GSK-3ß activity and cognitive function were analyzed by regression and mediating effect analyses, respectively. RESULTS: T2DM patients with ApoE ε4 but not ApoE ε2 haplotype showed poorer cognitive function and elevated platelet GSK-3ß activity, when using ApoE ε3 as reference. The elevation of GSK-3ß activity was positively correlated the diabetes duration, as well as plasma glycated hemoglobin (HbA1c) and glucose levels. Moreover, correlation and regression analysis also revealed significant pairwise correlations among GSK-3ß activity, ApoE gene polymorphism and cognitive function. Lastly, using Baron and Kenny modeling, we unveiled a mediative role of GSK-3ß activity between ApoE ε4 and cognitive impairment. CONCLUSION: We reported here that the upregulation of GSK-3ß activity mediates the exacerbation of cognitive impairment by ApoE ε4-enhanced cognitive impairment in T2DM patients, suggesting GSK-3ß inhibitors as promising drugs for preserving cognitive function in T2DM patients, especially to those with ApoE ε4 genotype.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Alelos , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Disfunção Cognitiva/genética , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Genótipo , Glicogênio Sintase Quinase 3 beta/genética
16.
Int Immunopharmacol ; 126: 111215, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38000234

RESUMO

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase(MMP-9)inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.


Assuntos
Aquaporinas , Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Doenças Neuroinflamatórias , Barreira Hematoencefálica/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Aquaporinas/metabolismo
17.
Zygote ; 32(1): 7-13, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38018399

RESUMO

Abnormalities in the zona pellucida (ZP) adversely affect oocyte maturation, embryo development and pregnancy outcomes. However, the assessment of severity is challenging. To evaluate the effects of different degrees of ZP abnormalities on embryo development and clinical outcomes, in total, 590 retrieval cycles were scored and divided into four categories (control, mild, moderate and severe) based on three parameters: perivitelline space, percentage of immature oocytes and percentage of oocytes with abnormal morphology. As the severity of abnormal ZP increased, both the number of retrieved oocytes and mature oocytes decreased. The fertilization rate did not differ significantly among groups. The rates of embryo cleavage and day-3 high-quality embryos in the mild group and the moderate group did not vary significantly between the two groups but were significantly higher than those in the severe group. The blastulation rates of the abnormal ZP groups were similar; however, they were lower than those of the control group. Moreover, the cycle cancellation rate of the severe abnormal ZP group was as high as 66.20%, which was significantly higher than that of the other three groups. Although the rates of cumulative clinical pregnancy and live births were lower than those in the control group, they were comparable among the abnormal ZP groups. There were no differences in the neonatal outcomes of the different groups. Together, ZP abnormalities show various degrees of severity, and in all patients regardless of the degree of ZP abnormalities who achieve available embryos, there will be an opportunity to eventually give birth.


Assuntos
Fertilização In Vitro , Zona Pelúcida , Gravidez , Feminino , Recém-Nascido , Humanos , Oócitos , Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas
18.
Luminescence ; 39(1): e4591, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37675627

RESUMO

Cerium has been widely used as a dopant in luminescent materials due to its unique electronic configurations. It is generally anticipated that the luminescence properties of rare-earth-doped materials are closely related to the local environment of activators, especially for Ce3+ . In addition, it is convenient to modulate its emission wavelength by adjusting the composition and structure. In this study, we systematically analyzed the microstructure of the Ce-doped CaYAlO4 system at atomic resolution. The quantitive results indicated that the structure distortion greatly influenced the valence state of the Ce dopant, which is critical to its luminescence efficiency. In addition, valence variations also exist from surface to inner structure due to the big distortion area around the surface. Our results unravel the interplay of local structure and valence transitions in Ce-doped aluminate phosphors, which has the potential to be applied in other luminescent materials.


Assuntos
Cério , Substâncias Luminescentes , Metais Terras Raras , Luminescência , Substâncias Luminescentes/química , Metais Terras Raras/química , Cério/química
19.
J Biochem Mol Toxicol ; 38(1): e23608, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38084607

RESUMO

This study aimed to explore the impact of different pH values of resuscitation fluid on traumatic hemorrhagic shock (THS), focusing on their effects on glycocalyx and inflammation. A rat model of THS was induced by hemorrhage from a left femur fracture, while an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HULEC-5a cell model was considered as an in vitro THS model. The lung tissue pathology and glycocalyx structure were assessed through hematoxylin-eosin (H&E) staining and transmission electron microscope examination. The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme-linked immunosorbent assay (ELISA). The expression of glycocalyx-related proteins, cell junction-related proteins, and proteins involved in the PI3K/Akt/NF-κB signaling pathway was analyzed by western blot. The results showed that both sodium bicarbonate Ringer's solution (BRS) and lactate Ringer's solution (LRS) were effective in restoring mean arterial pressure and heart rate in THS rats. However, LRS has a stronger impact on promoting inflammation and damaging the glycocalyx compared with BRS. In OGD/R-induced HULEC-5a cells, a pH of 7.4 and 6.5 increased inflammation and disrupted the glycocalyx, while a pH of 8.1 had no significant effect on inflammation or glycocalyx. Furthermore, the PI3K/Akt/NF-κB signaling pathway was activated by fluid resuscitation and different pH values. However, the activating effect of BRS and pH 8.1 on the PI3K/Akt/NF-κB signaling pathway was milder compared with LRS and pH6.5. In conclusion, an alkaline recovery environment was more beneficial for the treatment of THS.


Assuntos
Lesão Pulmonar , Choque Hemorrágico , Ratos , Animais , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Choque Hemorrágico/patologia , Solução de Ringer , Soluções Isotônicas/química , Soluções Isotônicas/farmacologia , Bicarbonato de Sódio , Proteínas Proto-Oncogênicas c-akt , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Ratos Sprague-Dawley , Hemorragia , Lactato de Ringer , Inflamação , Modelos Animais de Doenças
20.
Aging (Albany NY) ; 15(22): 13134-13149, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37983179

RESUMO

BACKGROUND: The prevalence of bone metastasis (BM) varies among primary cancer patients, and it has a significant impact on prognosis. However, there is a lack of research in this area. This study aims to explore the clinical characteristics, prevalence, and risk factors, and to establish a prognostic classification system for pan-cancer patients with BM. METHODS: The data obtained from the Surveillance, Epidemiology and End Results database were investigated. The prevalence and prognosis of patients with BM were analyzed. Hierarchical clustering was used to develop a prognostic classification system. RESULTS: From 2010 to 2019, the prevalence of BM has increased by 41.43%. BM most commonly occurs in cancers that originate in the adrenal gland, lung and bronchus and overlapping lesion of digestive systems. Negative prognostic factors included older age, male sex, poorer grade, unmarried status, low income, non-metropolitan living, advanced tumor stages, previous chemotherapy, and synchronous liver, lung, and brain metastasis. Three categories with significantly different survival time were identified in the classification system. CONCLUSIONS: The clinical features, prevalence, risk factors, and prognostic factors in pan-cancer patients with BM were investigated. A prognostic classification system was developed to provide survival information and aid physicians in selecting personalized treatment plans for patients with BM.


Assuntos
Neoplasias Ósseas , Humanos , Masculino , Prognóstico , Prevalência , Osso e Ossos , Fatores de Risco
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