Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 797
Filtrar
1.
Methods Mol Biol ; 2594: 107-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36264492

RESUMO

Deregulation of transcription factors is critical to hallmarks of cancer. Genetic mutations, gene fusions, amplifications or deletions, epigenetic alternations, and aberrant post-transcriptional modification of transcription factors are involved in the regulation of various stages of carcinogenesis, including cancer initiation, progression, and metastasis. Thus, targeting the dysfunctional transcription factors may lead to new cancer therapeutic strategies. However, transcription factors are conventionally considered as "undruggable." Here, we summarize the recent progresses in understanding the regulation of transcription factors in cancers and strategies to target transcription factors and co-factors for preclinical and clinical drug development, particularly focusing on c-Myc, YAP/TAZ, and ß-catenin due to their significance and interplays in cancer.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , beta Catenina , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Carcinogênese/genética
2.
J Colloid Interface Sci ; 630(Pt B): 426-435, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36334479

RESUMO

Pure phase MoS2 has low conductivity, but with high theoretical specific capacity, and WS2 possesses a high intrinsic conductivity, but suffer from rapid capacity fading. Predictably, the combination of these two transition metal sulfide compounds can complement each other and improve electrochemical performance comprehensively. Whereas, bimetallic phase sulfide of MoS2 and WS2 composites have not been researched in SIBs. In this paper, 1T metallic phase MoS2 and WS2 vertically growth on flexible carbon cloth (CC) surface (1T-MoS2@WS2@CC) by a simple hydrothermal method. The electrochemical performance was improved by heterojunction synergistic effect and the enhanced interlayers of the composite material. Specifically, the superelevation reversible capacity of 529.4 mAh/g can be obtained even after 100 cycles at the current density of 100 mA g-1, and the 259.2 mAh/g capacity can be maintained even at high current density of 1000 mA g-1 after 60 cycles. Besides, the designed 1T-MoS2@WS2@CC composite material has excellent rate performance and cycle stability which are guarantee for battery core performance. Thus, there is every reason to believe that the advanced 1T-MoS2@WS2@CC electrode material has great potential in the future high performance energy storage devices.

3.
Sci Total Environ ; 855: 158880, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36130629

RESUMO

Lead dioxide (PbO2) materials have been widely employed in various fields such as batteries, electrochemical engineering, and more recently environmental engineering as anode materials, due to their unique physicochemical properties. Key performances of PbO2 electrodes, such as energy efficiency and space-time yield, are influenced by morphological as well as compositional factors. Micro-nano structure regulation and decoration of metal/non-metal on PbO2 is an outstanding technique to revamp its electrocatalytic activities and enhance environmental engineering efficiency. The aim of this review is to comprehensively summarize the recent research progress in the morphology control, the structure constructions, and the element doping of PbO2 materials, further with many environmental application cases evaluated. Concerning electrochemical environmental engineering, the lead dioxide employed in chemical oxygen demand detection, ozone generators, and wastewater treatment has been comprehensively reviewed. In addition, the future research perspectives, challenges and the opportunities on PbO2 materials for environmental applications are proposed.


Assuntos
Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Titânio/química , Oxirredução , Óxidos/química , Eletrodos
4.
J Hazard Mater ; 443(Pt A): 130177, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36308932

RESUMO

Disinfection plays an essential role in waterborne pathogen control and disease prevention, especially during the COVID-19 pandemic. Catalyst-free solar light/periodate (PI) system has recently presented great potential in water disinfection, whereas the in-depth chemical and microbiological mechanisms for efficient bacterial inactivation remain unclear. Our work delineated firstly the critical role of singlet oxygen, instead of reported hydroxyl radicals and superoxide radicals, in dominating bacterial inactivation by the PI/simulated sunlight (SSL) system. Multi-evidence demonstrated the prominent disinfection performance of this system for Staphylococcus aureus in terms of culturability (> 6 logs CFU), cellular integrity, and metabolic activity. Particularly, the excellent intracellular DNA removal (> 95%) indicated that PI/SSL system may function as a selective disinfection strategy to diminish bacterial culturability without damaging the cell membrane. The PI/SSL system could also effectively inhibit bacterial regrowth for > 5 days and horizontal gene transfer between E. coli genera. Nontargeted metabolomic analysis suggested that PI/SSL system inactivated bacteria by triggering the accumulation of intracellular reactive oxygen species and the depletion of reduced glutathione. Additionally, the PI/SSL system could accomplish simultaneous micropollutant removal and bacterial inactivation, suggesting its versatility in water decontamination. Overall, this study deciphers more comprehensive antibacterial mechanisms of this environmentally friendly disinfection system, facilitating the technical development and application of the selective disinfection strategy in environmental pathogen control.


Assuntos
COVID-19 , Purificação da Água , Humanos , Desinfecção , Oxigênio Singlete , Escherichia coli , Pandemias , Água/farmacologia
5.
Front Pharmacol ; 13: 930593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386221

RESUMO

Acute respiratory distress syndrome (ARDS) is a common critical illness in respiratory care units with a huge public health burden. Despite tremendous advances in the prevention and treatment of ARDS, it remains the main cause of intensive care unit (ICU) management, and the mortality rate of ARDS remains unacceptably high. The poor performance of ARDS is closely related to its heterogeneous clinical syndrome caused by complicated pathophysiology. Based on the different pathophysiology phases, drugs, protective mechanical ventilation, conservative fluid therapy, and other treatment have been developed to serve as the ARDS therapeutic methods. In recent years, there has been a rapid development in nanomedicine, in which nanoparticles as drug delivery vehicles have been extensively studied in the treatment of ARDS. This study provides an overview of pharmacologic therapies for ARDS, including conventional drugs, natural medicine therapy, and nanomedicine. Particularly, we discuss the unique mechanism and strength of nanomedicine which may provide great promises in treating ARDS in the future.

6.
Heliyon ; 8(11): e11399, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36387469

RESUMO

Lung adenocarcinoma (LUAD) is one of the world's commonest malignancies with a high fatality rate. Chemokines not only regulate immune response but also participate in tumor development and metastasis and yet the mechanism of chemokines in LUAD remains unclear. In this study, transcriptional expression profiles, mutation data, and copy number variation data were downloaded from The Cancer Genome Atlas (TCGA). Risk gene protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA). Gene Expression Omnibus (GEO) data was used to validate the prognostic model. We summarized the genetic mutation variation landscape of chemokines. The risk prognosis model was developed based on differentially expressed chemokines, and patients in the high-risk score (RS) group had lower survival rates. Gene Set Enrichment Analysis (GSEA) revealed that high-RS patients were associated with metabolic transformation pathways, while low-RS patients were associated with immune-related pathways. Compared with the high-RS group, the low-RS group had higher immune/stromal/estimate scores calculated by the ESTIMATE package. The proportion of immune cells obtained using the CIBERSORT package was significantly different between the two groups. Most of the immune checkpoints were highly expressed in low-RS samples. Finally, we discovered that the lncRNA MIR17HG/AC009299.3/miR-21-5p/CCL20 regulatory network might be crucial in the pathogenesis of LUAD. In conclusion, we developed a risk signature and chemokine-related competing endogenous RNA (ceRNA) network.

7.
Elife ; 112022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36398861

RESUMO

The TEA domain (TEAD) transcription factor forms a transcription co-activation complex with the key downstream effector of the Hippo pathway, YAP/TAZ. TEAD-YAP controls the expression of Hippo-responsive genes involved in cell proliferation, development, and tumorigenesis. Hyperactivation of TEAD-YAP activities is observed in many human cancers, and is associated with cancer cell proliferation, survival and immune evasion. Therefore, targeting the TEAD-YAP complex has emerged as an attractive therapeutic approach. We previously reported that the mammalian TEAD transcription factors (TEAD1-4) possess auto-palmitoylation activities and contain an evolutionarily conserved palmitate-binding pocket (PBP), which allows small molecule modulation. Since then, several reversible and irreversible inhibitors have been reported by binding to PBP. Here, we report a new class of TEAD inhibitors with a novel binding mode. Representative analog TM2 shows potent inhibition of TEAD auto-palmitoylation both in vitro and in cells. Surprisingly, the co-crystal structure of the human TEAD2 YAP-binding domain (YBD) in complex with TM2 reveals that TM2 adopts an unexpected binding mode by occupying not only the hydrophobic PBP, but also a new side binding pocket formed by hydrophilic residues. RNA-seq analysis shows that TM2 potently and specifically suppresses TEAD-YAP transcriptional activities. Consistently, TM2 exhibits strong anti-proliferation effects as a single agent or in combination with a MEK inhibitor in YAP-dependent cancer cells. These findings establish TM2 as a promising small molecule inhibitor against TEAD-YAP activities and provide new insights for designing novel TEAD inhibitors with enhanced selectivity and potency.

8.
Nat Commun ; 13(1): 6744, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347861

RESUMO

Targeting TEAD autopalmitoylation has been proposed as a therapeutic approach for YAP-dependent cancers. Here we show that TEAD palmitoylation inhibitor MGH-CP1 and analogues block cancer cell "stemness", organ overgrowth and tumor initiation in vitro and in vivo. MGH-CP1 sensitivity correlates significantly with YAP-dependency in a large panel of cancer cell lines. However, TEAD inhibition or YAP/TAZ knockdown leads to transient inhibition of cell cycle progression without inducing cell death, undermining their potential therapeutic utilities. We further reveal that TEAD inhibition or YAP/TAZ silencing leads to VGLL3-mediated transcriptional activation of SOX4/PI3K/AKT signaling axis, which contributes to cancer cell survival and confers therapeutic resistance to TEAD inhibitors. Consistently, combination of TEAD and AKT inhibitors exhibits strong synergy in inducing cancer cell death. Our work characterizes the therapeutic opportunities and limitations of TEAD palmitoylation inhibitors in cancers, and uncovers an intrinsic molecular mechanism, which confers potential therapeutic resistance.


Assuntos
Neoplasias , Fosfatidilinositol 3-Quinases , Humanos , Lipoilação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição de Domínio TEA/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36377619

RESUMO

BACKGROUND: Pulmonary transit time (PTT) and pulmonary pulse wave transit time (pPTT) are useful parameters for the evaluation of cardiopulmonary circulation and vascular alterations, but their relationship remains unknown. The aim of this study was to investigate the correlation between PTT and pPTT. METHODS: A total of 60 healthy volunteers were involved in this study. They were divided into two groups (30 participants per group): <50 years and >50 years. They all underwent Doppler echocardiography of pulmonary vein flow and contrast echocardiography with the measurement of pPTT and PTT, respectively. The correlation between PTT and pPTT was deduced. RESULTS: Compared with Group of <50 years, there was a significant increment in left atrial volume index, left atrial pressure and pulmonary artery stiffness but a significant reduction in acceleration times of pulmonary artery flow in Group of >50 years (p < 0.05). Group >50 years had longer PTT and but reduced normalized PTT by R-R interval (NPTT), reduced normalized pPTT by R-R interval (NpPTT) than Group <50 years (p < 0.05), while there was no significant difference in pPTT between the two groups (p > 0.05). PTT and NPTT were all negatively correlated with pPTT and NpPTT. The statistically significant strongest correlation was observed between PTT and NpPTT (r = -0.886, p < 0.0001). The regression equation for them was y = 7.4396-13.095x (R2 = 0.785; p < 0.001), where x and y represent NpPTT and PTT, respectively. CONCLUSION: PTT had close relation with pPTT in normal subjects. From the regression equation for them, we can get the value of PTT simply and easily by non-invasively measured pPTT.

10.
Mol Ther Oncolytics ; 27: 204-223, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36420306

RESUMO

Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.

11.
Front Immunol ; 13: 1024931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341345

RESUMO

The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptome sequencing datasets and performs a series of silico analyses as nicely as validation of molecular biology techniques. A core set of immune escape related genes was identified through Lawson et al. and the ImmPort portal. The differential proteins were identified through the cBioPortal database. Regression analysis was used to profile independent prognostic factors. Correlation with the level of immune cell infiltration was evaluated by multiple algorithms. The capacity of LCK to predict response was assessed in two independent immunotherapy cohorts. High LCK expression is associated with better prognosis, high levels of TILs and better clinical staging. Pathway analysis showed that high expression of LCK was significantly associated with activation of multiple tumor pathways as well as immune-related pathways. LCK expression tends to be higher in immunotherapy-responsive patients and those with lower IC50s treated with chemotherapeutic agents. RT-qPCR detected that LCK expression was significantly upregulated in melanoma cell lines. Single-cell transcriptome analysis showed that LCK was specifically highly expressed on T cells. CellChat analysis confirmed that LCK in C2 subpopulations and T cell subpopulations exerted immune promotion between cells by binding to CD8 receptors. In conclusion, LCK is a reliable biomarker for melanoma and will contribute to its immunotherapy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma , Humanos , Prognóstico , Biomarcadores Tumorais/metabolismo , Melanoma/patologia , Microambiente Tumoral/genética
12.
Clin Exp Immunol ; 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36370151

RESUMO

Non-small cell lung cancer (NSCLC) is the primary reason of tumor morbidity and mortality worldwide. We aimed to study the transfer process of S100A4 between cells and whether it affected NSCLC development by affecting STAT3 expression. First, S100A4 expression in NSCLC cells was measured. The exosomes in MRC-5, A549, and H1299 cells were isolated and identified. We constructed si-S100A4 and si-PD-L1 to transfect A549 cells and oe-S100A4 to transfect H1299 cells, and tested the transfection efficiency. Cell function experiments were performed to assess cell proliferation, clone number, apoptosis, cell cycle, migration and invasion abilities. In addition, ChIP was applied to determine the targeting relationship between S100A4 and STAT3. Next, we explored NSCLC cell-derived exosomes role in NSCLC progress by transmitting S100A4. Finally, we verified the function of exosome-transmitted S100A4 in NSCLC in vivo. High expression of S100A4 was secreted by exosomes. After knocking down S100A4, cell proliferation ability was decreased, clones number was decreased, apoptosis was increased, G1 phase was increased, S phase was repressed, and migration and invasion abilities were also decreased. ChIP validated STAT3 and PD-L1 interaction. After knocking down S100A4, PD-L1 expression was decreased, while ov-STAT3 reversed the effect of S100A4 on PD-L1 expression. Meanwhile, S100A4 inhibited T cell immune activity by activating STAT3. In addition, knockdown of PD-L1 inhibited cell proliferation, migration and invasion. NSCLC cell-derived exosomes promoted cancer progression by transmitting S100A4 to activate STAT3 pathway. Finally, in vivo experiments further verified that exosome-transmitted S100A4 promoted NSCLC progression. Exosome-transmitted S100A4 induces immunosuppression and the development of NSCLC by activating STAT3.

13.
Front Immunol ; 13: 1026076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311731

RESUMO

Background: Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear. Methods: Data were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat. Results: The expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells. Conclusions: Dysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.


Assuntos
Microambiente Tumoral , Neoplasias Uveais , Humanos , Antígenos HLA-C/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismo , Neoplasias Uveais/patologia , Proteínas de Ligação ao Cálcio
14.
Mol Psychiatry ; 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36280756

RESUMO

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

15.
ACS Omega ; 7(39): 35063-35068, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36211056

RESUMO

Chlorfortunones A (1) and B (2), two novel sesquiterpenoid dimers, were isolated from the roots of Chloranthus fortunei. Their structures were elucidated by spectroscopic analysis and X-ray diffraction analysis. Compounds 1 and 2 represent a new type of sesquiterpenoid dimer possessing an unprecedented 3/5/6/6/6/5 hexacyclic system with a unique dispiro[4,2,5,2]pentadecane-6,10,14-trien moiety. A plausible biosynthetic pathway of 1 and 2 was proposed. Compound 1 showed transforming growth factor (TGF)-ß inhibitory activity in MDA-MB-231 cells.

16.
Front Cell Infect Microbiol ; 12: 998748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204652

RESUMO

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus; however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , MicroRNAs , RNA Longo não Codificante , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , RNA Circular , RNA Longo não Codificante/genética , RNA Mensageiro/genética , SARS-CoV-2/genética
17.
Genet Res (Camb) ; 2022: 2276175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101746

RESUMO

Background: Ultrafiltration failure remains one of the most severe complications of long-term peritoneal dialysis (PD), which results in death. This study aimed to characterize the circulating exosomal microRNA (miRNA) profiles associated with ultrafiltration failure and explore its underlying mechanisms. Methods: Exosomes were isolated from the peritoneal dialysis effluent (PDE) of patients with ultrafiltration failure or success using the ultracentrifugation method, and then transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot were used for exosome characterization. After that, the isolated exosomes were sent for small RNA sequencing, and eight differentially expressed miRNAs (DE-miRNAs) were chosen for RT-qPCR validation. Results: TEM, NTA, and western blot revealed that exosomes were successfully isolated. After sequencing, 70 DE-miRNAs involved in ultrafiltration were identified, including 41 upregulated ones and 29 downregulated ones. Functional analyses revealed that these DE-miRNAs were significantly enriched in pathways of cancer, ubiquitin-mediated proteolysis, axon orientation, and the Rap1 and Ras signaling pathways. In addition, the consistency rate of RT-qPCR and sequencing results was 75%, which indicated the relatively high reliability of the sequencing data. Conclusions: Our findings implied that these DE-miRNAs may be potential biomarkers of ultrafiltration failure, which would help us to discover novel therapeutic targets/pathways for ultrafiltration failure in patients with end-stage renal disease.


Assuntos
MicroRNA Circulante , Exossomos , MicroRNAs , Diálise Peritoneal , MicroRNA Circulante/metabolismo , Exossomos/genética , Exossomos/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Reprodutibilidade dos Testes , Ultrafiltração
18.
Andrologia ; : e14568, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36054412

RESUMO

This study aimed to assess the relationship between 25(OH) levels and erectile dysfunction (ED), particularly arteriogenic ED (A-ED). From September 2020 to January 2022, 150 patients diagnosed with ED by the International Index of Erectile Function-5 (IIEF-5) questionnaire were included. All patients were classified as organic ED and psychological ED by nocturnal penile tumescence and rigidity (NPTR) examination. Organic ED patients were divided into A-ED and NA-ED by penile doppler ultrasound (PDU) examination. Finally, 150 patients complaining of ED were enrolled in our study. 25(OH)D levels were significantly lower in patients with organic ED (18.24 ± 6.04 ng/ml) than in patients with psychogenic ED (20.90 ± 8.79 ng/ml) (p = 0.032). In A-ED and NA-ED, the mean of peak systolic flow velocity (PSV) values was 18.94 ± 5.28 cm/s and 51.57 ± 15.42 cm/s (p < 0.001), and the mean of 25(OH)D was 15.66 ± 5.86 ng/ml and 20.48 ± 5.90 ng/ml, respectively (p < 0.001). The results showed that 25(OH)D levels were positively correlated with IIEF-5 scores and the PSV values in A-ED patients. The 25(OH)D cut-off value differentiating between A-ED and NA-ED was 15.05 ng/ml. Low 25(OH)D levels may be an independent risk factor for ED, especially A-ED. ED patients should routinely undergo serum 25(OH)D level measurement, and 25(OH)D replacement therapy is necessary for patients with low vitamin D levels.

19.
J Adv Res ; 40: 263-276, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36100331

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated. OBJECTIVES: Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei Radix et Rhizoma and Coptidis Rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC. METHODS: TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system. RESULTS: TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis. CONCLUSION: Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.


Assuntos
Antineoplásicos , Berberina , Colite Ulcerativa , Colite , Animais , Antineoplásicos/uso terapêutico , Benzopiranos , China , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos , Salicilatos , Taninos/metabolismo , Proteínas de Junções Íntimas/metabolismo , Distribuição Tecidual
20.
J Integr Neurosci ; 21(5): 139, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36137953

RESUMO

As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.


Assuntos
Esquizofrenia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Esquizofrenia/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...