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1.
BMC Cancer ; 24(1): 79, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225540

RESUMO

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.


Assuntos
MicroRNAs , RNA Longo não Codificante , Rabdomiossarcoma , Serina-Treonina Quinases TOR , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Rabdomiossarcoma/genética , Rabdomiossarcoma/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima
2.
BMC Cardiovasc Disord ; 24(1): 150, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475731

RESUMO

BACKGROUND AND AIMS: The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. METHODS: This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. RESULTS: This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. CONCLUSION: According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.


Assuntos
Adiposidade , Hipertensão , Adulto , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Adulto Jovem , Idoso , Estudos Prospectivos , Fatores de Risco , Obesidade/epidemiologia , Índice de Massa Corporal , Relação Cintura-Quadril , Circunferência da Cintura , Razão Cintura-Estatura
3.
Inorg Chem ; 61(12): 4938-4947, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35275482

RESUMO

Attracted by the exceptional structural rigidity and inherent porous structures of the Hf-based metal-organic frameworks (MOFs), we adopted a rapid synthesis approach to preparing three nanoscale MOFs, Hf-UiO-66 (1), Hf-UiO-66-(OH)2 (2), and Hf-UiO-66-NH2 (3), and systematically explored the water-assisted proton conductivities of the original ones and the post-modified products. Interestingly, the proton conductivities (σ) of all three MOFs exhibit significant temperature and humidity dependence. At 98% RH and 100 °C, their optimal σ values can reach up to 10-3 S·cm-1. Consequently, imidazole units are loaded into 1-3 to obtain related MOFs, Im@1, Im@2, and Im@3, and the σ values of the imidazole-loaded products are boosted to 10-2 S·cm-1. Note that these modifications not only do not change the frameworks of the pristine MOFs but also do not affect their high chemical and water stability. The proton-conductive mechanisms of these MOFs before and after modification have been thoroughly discussed based on structural analyses, N2 and H2O vapor adsorptions, and activation energy values. The excellent structural stability as well as the durability and stability of their proton conduction ability indicate that these MOFs can be used in the field of fuel cells and so on.

4.
Bioorg Chem ; 103: 104172, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890991

RESUMO

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway works as the key regulator against oxidative stress damage in many cells and organs. It has been a widely proposed therapeutic target for neurodegenerative diseases, including Alzheimer's disease (AD). This study aimed at determining the neuroprotective activity of 9 (NXPZ-2), a small-molecule compound that directly inhibits the Keap1-Nrf2 protein-protein interaction, in an amyloid beta 1-42 (Aß1-42) oligomer intracerebroventricularly (i.c.v.) injected mouse model. Behavioral tests showed that NXPZ-2 treatment dose-relatedly ameliorated learning and memory dysfunction in Aß1-42-treated mice. HE and Nissl staining showed that NXPZ-2 improved brain tissue pathological changes in AD mice by increasing neuron quantity and function. Western blot analysis of the hippocampus and cortex showed up-regulated Nrf2 in whole cell lysate, with increased nuclear translocation to increase Nrf2-targeted antioxidant enzymes (HO-1, NQO-1) and decreased p-Tau in NXPZ-2-treated mice. ELISA results showed that NXPZ-2 treatment increased serum Nrf2 and significantly decreased serum Aß1-42 levels in AD mice. Furthermore, hippocampal and cortical superoxide dismutase (SOD) and glutathione (GSH) levels increased, while malondialdehyde (MDA) levels decreased. No obvious toxicity was observed in primary cultured mouse cortical neurons and organs with NXPZ-2 treatment. No ameliorative effect was observed of NXPZ-2 in Nrf2 knockout AD mice. Collectively, our findings demonstrated that NXPZ-2 could be a promising therapeutic agent against AD, and provided the first set of experimental evidence, in a mouse model, to support Keap1-Nrf2 interaction as a validated target for the Nrf2 reactivation in AD.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Doença de Alzheimer , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
5.
Environ Res ; 190: 109931, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32781323

RESUMO

Removal of toxic aniline from wastewater is of great importance in industrial manufacture. Traditional electrochemical methods encounter obstacles such as high energy consumption in mineralization and severe electrode passivation in electro-polymerization. In this paper, we report a practical electro-polymerization method by using Ti/Sb-SnO2/PbO2 anode to treat high concentration aniline wastewater. The cyclic voltammetric experiment was conducted and the problem of electrode passivation was solved by increasing the electrode potential. In the experiments of treating aniline wastewater, the produced solid polymer can separate from water rather than sticking to electrode surface. Elemental analysis shows that oxygen is incorporated in the polymer. Experiments were conducted under different conditions, including current density, pH and initial concentration of aniline and Na2SO4. The electro-polymerization route accounts for nearly 50% contribution in the removal of chemical oxygen demand (COD). Our electro-polymerization method gives an apparent current efficiency (ACE) of 232.15% and an energy consumption (Ep) of 0.008658 kWh g-1COD-1 when half of COD is removed at a current density of 15 mA cm-2, pH of 7.0, initial aniline concentration of 1.2 g L-1 and Na2SO4 concentration of 4 g L.-1.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Compostos de Anilina , Eletroquímica , Oxirredução , Polimerização , Eliminação de Resíduos Líquidos , Águas Residuárias
6.
J Environ Manage ; 253: 109680, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634748

RESUMO

Microalgae produce increased lipid content accompanied by a significant decrease in cell density with decreasing nitrate concentration. Magnetic fields (MF) have been reported as a factor that could accelerate metabolism and growth in microalgae culture. Thus, this study aimed to optimize the influence of MF and nitrate concentration (sodium nitrate, N) on the growth and lipid productivity of Nannochloropsis oculata. A single-factor experiment integrated with response surface methodology (RSM) via central composite design (CCD) was performed. The results showed that the maximum specific growth rate (0.24 d-1) and maximum lipid productivity (38 mg L-1 d-1) obtained in this study were higher than those of the control culture (by 166% and 103%, respectively). This study also found that the two-way interaction term MF × N had a significant effect on cell growth but not on lipid production. It was concluded that to design appropriate MF for enhanced lipid productivity due to cell growth, further research must focus on developing an understanding of the relationship between the bioeffects of the magnetic field and the proteomic changes involved in lipid accumulation strategies. This approach would enable the design of conditions to obtain inexpensive high-value products from N. oculata.


Assuntos
Microalgas , Estramenópilas , Biomassa , Lipídeos , Campos Magnéticos , Proteômica
7.
Bioinformatics ; 34(1): 109-111, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968788

RESUMO

Summary: Advances in next generation sequencing have generated massive amounts of short reads. However, assembling genome sequences from short reads still remains a challenging task. Due to errors in reads and large repeats in the genome, many of current assembly tools usually produce just collections of contigs whose relative positions and orientations along the genome being sequenced are still unknown. To address this issue, a scaffolding process to order and orient the contigs of a draft genome is needed for completing the genome sequence. In this work, we propose a new scaffolding tool called CSAR that can efficiently and more accurately order and orient the contigs of a given draft genome based on a reference genome of a related organism. In particular, the reference genome required by CSAR is not necessary to be complete in sequence. Our experimental results on real datasets have shown that CSAR outperforms other similar tools such as Projector2, OSLay and Mauve Aligner in terms of average sensitivity, precision, F-score, genome coverage, NGA50 and running time. Availability and implementation: The program of CSAR can be downloaded from https://github.com/ablab-nthu/CSAR. Contact: hchiu@mail.ncku.edu.tw or cllu@cs.nthu.edu.tw. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Mapeamento de Sequências Contíguas/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Software , Algoritmos , Bactérias/genética , Genoma , Genômica/métodos , Humanos
8.
Opt Express ; 27(2): 1164-1177, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30696184

RESUMO

In recent years, head-mounted display technologies have greatly advanced. In order to overcome the accommodation-convergence conflict, light field displays reconstruct three-dimensional (3D) images with a focusing cue but sacrifice resolution. In this paper, a hybrid head-mounted display system that is based on a liquid crystal microlens array is proposed. By using a time-multiplexed method, the display signals can be divided into light field and two-dimensional (2D) modes to show comfortable 3D images with high resolution compensated by the 2D image. According to the experimental results, the prototype supports a 12.28 ppd resolution in the diagonal direction, which reaches 82% of the traditional virtual reality (VR) head-mounted display (HMD).

9.
BMC Cancer ; 19(1): 181, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819119

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. METHODS: To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. RESULTS: After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. CONCLUSIONS: This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China/epidemiologia , Mapeamento Cromossômico , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Padrões de Herança , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de Chances
10.
J Mater Sci Mater Med ; 28(1): 16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28000112

RESUMO

Calcification is a major factor that limits the durability of bioprosthetic valve. A novel bovine pericardial tissue treated with aldehyde capping chemistry and glycerolization was evaluated for its resistance to calcification in comparison with porcine tissues treated with amino oleic acid and bovine pericardial tissue with ethanol rinsing in a rabbit intramuscular model. Tissue discs from the test and control tissues were implanted in rabbits for 60 days. The explanted discs were subject to X-ray imaging, calcium quantification and histology analysis. The test tissue showed 95 and 96 % reduction in calcification in comparison with amino oleic acid treatment and ethanol rinsing treatment, respectively. In addition, the test tissue showed the least inflammatory response as evidenced by a reduced amount of macrophages and giant cells in histology analysis. Furthermore, the aldehyde analysis of the pre-implanted samples showed associated reduction in free aldehyde levels with the test tissue. The reduction in calcification is consistent with previously reported results and is hypothesized to be attributed to the capping of free aldehydes in the test tissue.


Assuntos
Aldeídos/química , Bioprótese , Calcinose/prevenção & controle , Pericárdio/metabolismo , Animais , Cálcio/análise , Bovinos , Etanol/farmacologia , Próteses Valvulares Cardíacas , Macrófagos/metabolismo , Teste de Materiais , Músculo Esquelético/metabolismo , Ácido Oleico/farmacologia , Falha de Prótese , Coelhos , Distribuição Aleatória , Suínos
11.
BMC Bioinformatics ; 17(Suppl 17): 469, 2016 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-28155633

RESUMO

BACKGROUND: A draft genome assembled by current next-generation sequencing techniques from short reads is just a collection of contigs, whose relative positions and orientations along the genome being sequenced are unknown. To further obtain its complete sequence, a contig scaffolding process is usually applied to order and orient the contigs in the draft genome. Although several single reference-based scaffolding tools have been proposed, they may produce erroneous scaffolds if there are rearrangements between the target and reference genomes or their phylogenetic relationship is distant. This may suggest that a single reference genome may not be sufficient to produce correct scaffolds of a draft genome. RESULTS: In this study, we design a simple heuristic method to further revise our single reference-based scaffolding tool CAR into a new one called Multi-CAR such that it can utilize multiple complete genomes of related organisms as references to more accurately order and orient the contigs of a draft genome. In practical usage, our Multi-CAR does not require prior knowledge concerning phylogenetic relationships among the draft and reference genomes and libraries of paired-end reads. To validate Multi-CAR, we have tested it on a real dataset composed of several prokaryotic genomes and also compared its accuracy performance with other multiple reference-based scaffolding tools Ragout and MeDuSa. Our experimental results have finally shown that Multi-CAR indeed outperforms Ragout and MeDuSa in terms of sensitivity, precision, genome coverage, scaffold number and scaffold N50 size. CONCLUSIONS: Multi-CAR serves as an efficient tool that can more accurately order and orient the contigs of a draft genome based on multiple reference genomes. The web server of Multi-CAR is freely available at http://genome.cs.nthu.edu.tw/Multi-CAR/ .


Assuntos
Mapeamento de Sequências Contíguas/métodos , Análise de Sequência de DNA/métodos , Software , Bactérias/genética , Genoma Bacteriano , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
13.
Biochem Biophys Res Commun ; 465(3): 387-93, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26255201

RESUMO

Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3'-untranslated region (3'-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3'-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-ß1 (TGF-ß1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis.


Assuntos
Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , MicroRNAs/metabolismo , PPAR gama/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Regulação para Baixo/genética , Cirrose Hepática/genética , Masculino , MicroRNAs/genética , PPAR gama/genética , Ratos , Ratos Sprague-Dawley
14.
Soft Matter ; 11(4): 646-54, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25515644

RESUMO

The Pickering emulsion process is an important and interesting way of forming hybrid soft matter particles stabilized by solid particles as surfactants instead of the extensive use of conventionally available organic surfactant molecules. This Highlight briefly reviews stimuli-responsive polymer/inorganic hybrid materials fabricated by Pickering emulsion polymerization along with the rheological characteristics of their electrorheological and magnetorheological smart fluids under electric and magnetic fields, respectively.

15.
Int Immunopharmacol ; 138: 112282, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38936058

RESUMO

Hypoxia is a hallmark of solid tumors. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, and CAF-derived exosomes are involved in cancer genesis and progression. Here, this work investigated the role and mechanism of exosomal circHIF1A derived from hypoxia-induced CAFs in hepatocellular carcinoma (HCC) tumorigenesis. CAFs isolated from fresh HCC tissues were incubated in normoxia or hypoxia condition (N/CAFs or H/CAFs), and then the exosomes from N/CAFs or H/CAFs were isolated for functional analysis. Cell proliferation, migration and invasion were analyzed by cell counting kit-8, colony formation, and transwell assays. Immune evasion was evaluated by measuring the cytotoxicity and viability of CD8+T cells. qRT-PCR and western blotting analyses were used for the level measurement of genes and proteins. The binding between Hu antigen R (HuR) and circHIF1A or Programmed death ligand 1 (PD-L1) was analyzed by RNA immunoprecipitation assay. Functionally, we found that CAFs, especially CAFs under hypoxic stress (H/CAFs), promoted the proliferation, migration, invasion and EMT progression in HCC cells, as well as induced immune escape by suppressing CD8+T cell cytotoxicity and activity in an exosome-dependent manner. H/CAFs-derived exosomes showed highly expressed circHIF1A, and could secrete circHIF1A into HCC cells via exosomes. The oncogenic effects of H/CAFs-secreted exosomes were abolished by circHIF1A knockdown. Mechanistically, circHIF1A interacted with HuR to stabilize PD-L1 expression in HCC cells. Meanwhile, circHIF1A silencing suppressed HCC cell proliferation, mobility and immune escape by regulating PD-L1 expression. In all, exosomal circHIF1A derived from hypoxic-induced CAFs promoted the proliferation, migration, invasion, EMT progression and immune escape in HCC cells by up-regulating PD-L1 expression in a HuR-dependent manner.


Assuntos
Antígeno B7-H1 , Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Proliferação de Células , Exossomos , Neoplasias Hepáticas , Evasão Tumoral , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Exossomos/metabolismo , Exossomos/imunologia , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Movimento Celular , Microambiente Tumoral/imunologia , Linfócitos T CD8-Positivos/imunologia , Animais
16.
Comput Struct Biotechnol J ; 23: 688-699, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38292476

RESUMO

The self-assembly of Aß peptides into toxic oligomers and fibrils is the primary cause of Alzheimer's disease. Moreover, the conformational transition from helix to sheet is considered a crucial step in the aggregation of Aß peptides. However, the structural details of this process still remain unclear due to the heterogeneity and transient nature of the Aß peptides. In this study, we developed an enhanced sampling strategy that combines artificial neural networks (ANN) with metadynamics to explore the conformational space of the Aß42 peptides. The strategy consists of two parts: applying ANN to optimize CVs and conducting metadynamics based on the resulting CVs to sample conformations. The results showed that this strategy achieved better sampling performance in terms of the distribution of sampled conformations. The sampling efficiency is increased by 10-fold compared to our previous Hamiltonian Exchange Molecular Dynamics (MD) and by 1000-fold compared to ordinary MD. Based on the sampled conformations, we constructed a Markov state model to understand the detailed transition process. The intermediate states in this process are identified, and the connecting paths are analyzed. The conformational transitions in D23-K28 and M35-V40 are proven to be crucial for aggregation. These results are helpful in clarifying the mechanism and process of Aß42 peptide aggregation. D23-K28 and M35-V40 can be identified as potential targets for screening and designing inhibitors of Aß peptide aggregation.

17.
Aging (Albany NY) ; 16(9): 7578-7595, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568089

RESUMO

BACKGROUND: Studies have shown that coagulation and fibrinolysis (CFR) are correlated with Hepatocellular carcinoma (HCC) progression and prognosis. We aim to build a model based on CFR-correlated genes for risk assessment and prediction of HCC patient. METHODS: HCC samples were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. The Molecular Signatures Database (MSigDB) was used to select the CFR genes. RiskScore model were established by single sample gene set enrichment analysis (ssGSEA), weighted correlation network analysis (WGCNA), multivariate Cox regression analysis, LASSO regression analysis. RESULTS: PCDH17, PGF, PDE2A, FAM110D, FSCN1, FBLN5 were selected as the key genes and designed a RiskScore model. Those key genes were Differential expressions in HCC cell and patients. Overexpression PDE2A inhibited HCC cell migration and invasion. The higher the RiskScore, the lower the probability of survival. The model has high AUC values in the first, third and fifth year prediction curves, indicating that the model has strong prediction performance. The difference analysis of clinicopathological features found that a great proportion of high clinicopathological grade samples showed higher RiskScore. RiskScore were positively correlated with immune scores and TIDE scores. High levels of immune checkpoints and immunomodulators were observed in high RiskScore group. High RiskScore groups may benefit greatly from taking traditional chemotherapy drugs. CONCLUSIONS: We screened CFR related genes to design a RiskScore model, which could accurately evaluate the prognosis and survival status of HCC patients, providing certain value for optimizing the clinical treatment of cancer in the future.


Assuntos
Coagulação Sanguínea , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Prognóstico , Coagulação Sanguínea/genética , Fibrinólise/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Feminino , Masculino , Perfilação da Expressão Gênica , Medição de Risco
18.
Int J Biol Macromol ; 275(Pt 1): 133336, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936568

RESUMO

Exosomes (Exo) generated from mesenchymal stem cells (MSCs) have great therapeutic potential in ischemia-reperfusion treatment. For best therapeutic effect, high quality Exo product and effective delivery system are indispensable. In this study, we developed a new strategy for ischemia-reperfusion recovery by combining MSCs 3D (3D-MSC) culturing technology to generate Exo (3D-MSC-Exo) and microneedle for topical delivery. Firstly, primary MSCs from neonatal mice were isolated and 3D cultured with gelatin methacryloyl (GelMA) hydrogel to prepare 3D-MSC-Exo. The 3D-MSC showed better viability and 3D-MSC-Exo exhibited more effective effects of reducing neuroinflammation, inhibiting glial scarring, and promoting angiogenesis. Subsequently, the biocompatible GelMA was used to construct microneedles for 3D-Exo delivery (GelMA-MN@3D-Exo). The results demonstrated GelMA microneedles had excellent 3D-Exo loading capacity and enabled continuous 3D-Exo release to maintain effective therapeutic concentrations. Furthermore, the rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic effect of GelMA-MN@3D-Exo in ischemia-reperfusion in vivo. Animal experiments showed that the GelMA-MN@3D-Exo system could effectively reduce the local neuroinflammatory reaction, promote angiogenesis and minimize glial scar proliferation in ischemia-reperfusion. The underlying reasons for the stronger neuroprotective effect of 3D-Exo was further studied using mass spectrometry and transcriptome assays, verifying their effects on immune regulation and cell proliferation. Taken together, our findings demonstrated that GelMA-MN@3D-Exo microneedle can effectively attenuate ischemia-reperfusion cell damage in the MCAO model, which provides a promising therapeutic strategy for ischemia-reperfusion recovery.


Assuntos
Exossomos , Gelatina , Células-Tronco Mesenquimais , Agulhas , Traumatismo por Reperfusão , Animais , Gelatina/química , Camundongos , Ratos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia , Metacrilatos/química , Masculino , Modelos Animais de Doenças , Hidrogéis/química , Ratos Sprague-Dawley , Infarto da Artéria Cerebral Média/terapia
19.
Int J Food Microbiol ; 421: 110806, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38941886

RESUMO

Lactic acid bacteria (LAB) are frequently used in meat fermentation, and mixed stater cultures are reported to perform better than single ones. Lactiplantibacillus plantarum 3-19 and Pediococcus pentosaceus 18-1 were chosen from 28 sour-meat-origin strains to examine the effects of single and combined inoculation on sour meat quality. Natural fermentation was used as a control to investigate changes in pH, water activity (aw), amino acid nitrogen (AN), texture, microbial diversity, and volatile organic compounds (VOCs) during fermentation. The pH and aw of each inoculation group were significantly decreased, and AN content was significantly increased. The inoculation of P. pentosaceus 18-1 significantly reduced putrescine, cadaverine, and tryptamine content (p < 0.05), while the inoculation of Lpb. plantarum 3-19 significantly reduced cadaverine amounts (p < 0.05). At the fermentation endpoint, the total biogenic amines content in the C group was 992.96 ± 14.07, which was 1.65, 2.57, and 3.07 times higher than that in the Lp, Pe, and M groups, respectively. The mixed inoculation group combined the advantages of both strains and decreased total biogenic amines most significantly. At the end of fermentation, the VOCs in C, Lp, Pe, and M groups were 10.11, 11.56, 12.45, and 13.39 times higher than those at the beginning of fermentation. Inoculation promoted the production of key VOCs (OAV > 2000) such as heptanal, octanal, and (E)-2-nonanal. The mixed inoculation group had the highest variety and content of VOCs and the highest content of the above key VOCs, significantly enhancing its fruity, floral, ester, and other aromas. Sensory evaluation indicated that the M group had the best overall acceptability. Finally, it was suggested that a combination of Lpb. plantarum 3-19 and P. pentosaceus 18-1 is a novel and efficient starter culture for processing sour meat since they lower the amounts of biogenic amines in the meat and promote the production of VOCs.


Assuntos
Aminas Biogênicas , Fermentação , Microbiologia de Alimentos , Pediococcus pentosaceus , Compostos Orgânicos Voláteis , Aminas Biogênicas/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Pediococcus pentosaceus/metabolismo , Lactobacillus plantarum/metabolismo , Carne/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Cadaverina/metabolismo
20.
Curr Med Imaging ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37921150

RESUMO

BACKGROUND: Lung ultrasound (LUS) is gaining recognition as an indispensable diagnostic tool in critical care. OBJECTIVE: The study aimed to characterize the global research landscape and trend of LUS with quantification and visualization approaches. METHODS: Documents related to LUS published between 2007 and 2023 were selected from the Web of Science Core Collection and identified. Visualization and statistical analysis were conducted with the VOSviewer 1.6.18, CiteSpace 5.7.R5, and Bibliometrix 4.1.0 Package, including analysis of the trend of global publications, prominent countries, active institutions, and funding agencies, key authors and journals, co-cited references, and keywords. RESULTS: A total of 3010 publications, including 2434 articles and 576 reviews, were retrieved. The output of LUS-related research has increased steadily over the years, especially after 2018. Italy (n=756; 25.12%) has shown the highest output, being the country with the highest total citations (23423 times). The most influential author was Gargani Luna with 52 documents, who worked at the Consiglio Nazionale delle Ricerche. Chest and Intensive Care Medicine with high citations and impact factor scores were the most influential journals. Besides "lung ultrasonography", the keywords developed included "coronavirus disease 2019 (COVID-19)", "acute respiratory distress syndrome", and "acute heart failure". CONCLUSION: Research output on LUS has increased steadily, especially after 2018. Italy and the United States are staying ahead in this field. Research collaboration still needs to be strengthened. This comprehensive analysis has presented the global research landscape and trends of LUS-related research, providing valuable information for researchers to pursue further exploration.

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