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1.
Geriatr Nurs ; 58: 200-207, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824882

RESUMO

There is a paucity of evidence on exercise interventions for frail older adults with diabetes. This scoping review aims to identify the scope of the current literature on the characteristics and effects of exercise interventions for frail older adults with diabetes. A search without time limitation was conducted in eight databases. 14 studies were finally included. Resistance exercise and multicomponent exercise were the most common types of exercise. There was considerable variation in the frequency, duration and intensity of exercise interventions. Studies reported improvements in frailty status, physical function, blood glucose and lipid levels and economic effectiveness. The most frequent combined interventions involved nutrition and education. Although evidence was limited, the potential benefits of exercise interventions for frail older adults with diabetes were substantial. Further high-quality studies are needed to explore the most effective and cost-saving exercise interventions for frail older adults with diabetes.

2.
J Phys Chem A ; 128(24): 4765-4774, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38840312

RESUMO

The development of the velocity map ion imaging (VMI) technique has greatly advanced the study of photodissociation dynamics. The high-resolution imaging study of the photodissociation allows for the acquisition of precise and detailed information on the fragments. This information can further provide more insight into the energy partition and potential pathways involved in the photodissociation process. In this study, we report the investigation on the photodissociation of OCS+ via the A2ΠΩ=1/2,3/2 states following the excitation of A2Π (ν1 0 ν3) ← X2Π (0 0 0) by using time-sliced VMI techniques in the ultraviolet region. Our investigation revealed significant mode-dependent recoil anisotropies and branching ratios of two product channels for both Ω = 1/2 and Ω = 3/2. The photolysis products also exhibited dramatic deviation in angular distributions and generally comparable kinetic energy distributions following the excitation to the same vibrational modes of A2ΠΩ states with two separate spin-orbit components. According to the observation in this study and previously reported photodissociation mechanisms of the OCS+ cations, the decay from the A2Π3/2 state was more likely via the internal conversion to high rovibrational states of the X2Π state, in comparison to the A2Π1/2 state.

3.
Colloids Surf B Biointerfaces ; 241: 114049, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38908043

RESUMO

The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the "one stone, three birds" strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.

4.
Med Sci Monit ; 30: e943414, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937949

RESUMO

BACKGROUND Sepsis-associated acute kidney injury (SA-AKI) is linked to high mortality rates and an unfavorable prognosis. Early identification of patients with poor prognosis is crucial. This study aimed to investigate the relationship between the systemic immune-inflammation index (SII) and mortality in this specific patient population. MATERIAL AND METHODS This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database. Data on patient demographics, comorbidities, vital signs, laboratory parameters, treatment usage, acute kidney injury staging, and renal replacement therapy were collected within 48 h of intensive care unit admission. Restricted cubic splines, Kaplan-Meier curves, and Cox regression models were used for analysis. Stratified analyses were performed on the basis of various factors. RESULTS In total, 7856 patients were included, with a median age of 66.9 years and a male-to-female ratio of 57.7%-42.3%. A J-shaped relationship was observed between SII and mortality risk. The lowest mortality risk occurred at an SII of 760.078×109/L. Compared to the reference group (second quartile of SII), the highest and third quartiles had increased 28-day mortality risk, with adjusted hazard ratios (HRs) of 1.33 (1.16-1.52) and 1.55 (1.36-1.77), respectively. Although a trend towards higher mortality hazard was observed in the lowest SII group (Q1), it was not statistically significant, with an adjusted HR of 1.15 (1-1.32). CONCLUSIONS In patients with SA-AKI, both low and high SII were associated with increased short-term mortality risk. The lowest mortality risk was observed at an SII of 760.078×109/L within a 28-day period.


Assuntos
Injúria Renal Aguda , Inflamação , Unidades de Terapia Intensiva , Sepse , Humanos , Masculino , Feminino , Estudos Retrospectivos , Sepse/mortalidade , Sepse/complicações , Sepse/imunologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/imunologia , Idoso , Pessoa de Meia-Idade , Prognóstico , Inflamação/complicações , Fatores de Risco , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier
5.
Materials (Basel) ; 17(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930372

RESUMO

Frequent removal and reapplication of wound dressings can cause mechanical disruption to the healing process and significant physical discomfort for patients. In response to this challenge, a dynamic covalent hydrogel has been developed to advance wound care strategies. This system comprises aldehyde functionalized chondroitin sulfate (CS-CHO) and thiolated hyaluronic acid (HA-SH), with the distinct ability to form in situ via thiol-aldehyde addition and dissolve on-demand via the thiol-hemithioacetal exchange reaction. Although rarely reported, the dynamic covalent reaction of thiol-aldehyde addition holds great promise for the preparation of dynamic hydrogels due to its rapid reaction kinetics and easy reversible dissociation. The thiol-aldehyde addition chemistry provides the hydrogel system with highly desirable characteristics of rapid gelation (within seconds), self-healing, and on-demand dissolution (within 30 min). The mechanical and dissolution properties of the hydrogel can be easily tuned by utilizing CS-CHO materials of different aldehyde functional group contents. The chemical structure, rheology, self-healing, swelling profile, degradation rate, and cell biocompatibility of the hydrogels are characterized. The hydrogel possesses excellent biocompatibility and proves to be significant in promoting cell proliferation in vitro when compared to a commercial hydrogel (HyStem® Cell Culture Scaffold Kit). This study introduces the simple fabrication of a new dynamic hydrogel system that can serve as an ideal platform for biomedical applications, particularly in wound care treatments as an on-demand dissolvable wound dressing.

6.
Small ; : e2312254, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874100

RESUMO

Nanoimprinting large-area structures, especially high-density features like meta lenses, poses challenges in achieving defect-free nanopatterns. Conventional high-resolution molds for nanoimprinting are often expensive, typically constructed from inorganic materials such as silicon, nickel (Ni), or quartz. Unfortunately, replicated nanostructures frequently suffer from breakage or a lack of definition during demolding due to the high adhesion and friction at the polymer-mold interface. Moreover, mold degradation after a limited number of imprinting cycles, attributed to contamination and damaged features, is a common issue. In this study, a disruptive approach is presented to address these challenges by successfully developing an anti-sticking nanocomposite mold. This nanocomposite mold is created through the co-deposition of nickel atoms and low surface tension polytetrafluoroethylene (PTFE) nanoparticles via electroforming. The incorporation of PTFE enhances the ease of polymer release from the mold. The resulting Ni-PTFE nanocomposite mold exhibits exceptional lubrication properties and a significantly reduced surface energy. This robust nanocomposite mold proves effective in imprinting fine, densely packed nanostructures down to 100 nm using thermal nanoimprinting for at least 20 cycles. Additionally, UV nanoimprint lithography (UV-NIL) is successfully performed with this nanocomposite mold. This work introduces a novel and cost-effective approach to reusable high-resolution molds, ensuring defect-reduction production in nanoimprinting.

7.
J Mater Chem B ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899871

RESUMO

Three-dimensional bioprinting is a potent biofabrication technique in tissue engineering but is limited by inadequate bioink availability. Plant-derived proteins are increasingly recognized as highly promising yet underutilized materials for biomedical product development and hold potential for use in bioink formulations. Herein, we report the development of a biocompatible plant protein bioink from pea protein isolate. Through pH shifting, ethanol precipitation, and lyophilization, the pea protein isolate (PPI) transformed from an insoluble to a soluble form. Next, it was modified with glycidyl methacrylate to obtain methacrylate-modified PPI (PPIGMA), which is photocurable and was used as the precursor of bioink. The mechanical and microstructural studies of the hydrogel containing 16% PPIGMA revealed a suitable compress modulus and a porous network with a pore size over 100 µm, which can facilitate nutrient and waste transportation. The PPIGMA bioink exhibited good 3D bioprinting performance in creating complex patterns and good biocompatibility as plenty of viable cells were observed in the printed samples after 3 days of incubation in the cell culture medium. No immunogenicity of the PPIGMA bioink was identified as no inflammation was observed for 4 weeks after implantation in Sprague Dawley rats. Compared with methacrylate-modified gelatin, the PPIGMA bioink significantly enhanced cartilage regeneration in vitro and in vivo, suggesting that it can be used in tissue engineering applications. In summary, the PPIGMA bioink can be potentially used for tissue engineering applications.

8.
Bioorg Med Chem ; 107: 117750, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776567

RESUMO

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.


Assuntos
Analgésicos , Hipoglicemiantes , Canais de Cátion TRPV , Animais , Humanos , Masculino , Camundongos , Ratos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Relação Dose-Resposta a Droga , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
9.
Anal Chem ; 96(23): 9379-9389, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38805056

RESUMO

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Animais , Fatores de Tempo , Análise de Dados
10.
Proc Natl Acad Sci U S A ; 121(23): e2322359121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38805286

RESUMO

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion-related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion-driven diseases.


Assuntos
Proteína Adaptadora GRB2 , Sistema de Sinalização das MAP Quinases , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas c-ret , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Proteínas ras , Humanos , Proteína Adaptadora GRB2/metabolismo , Proteína Adaptadora GRB2/genética , Células HEK293 , Proteínas de Fusão Oncogênica/metabolismo , Proteínas de Fusão Oncogênica/genética , Fosforilação , Proteínas Proto-Oncogênicas c-ret/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas ras/metabolismo , Proteínas ras/genética , Transdução de Sinais , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética
12.
Int J Biol Macromol ; 271(Pt 2): 132442, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38761903

RESUMO

During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Macrófagos , Agulhas , Polissacarídeos , Espécies Reativas de Oxigênio , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/administração & dosagem , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Polímeros/química , Células RAW 264.7 , Inflamação/tratamento farmacológico , Humanos , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Citocinas/metabolismo , Morfinanos
13.
Heliyon ; 10(10): e31478, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38818139

RESUMO

Background and objective: Circular RNAs (circRNAs) have garnered considerable attention in the study of various human diseases due to their ubiquitous expression and potential biological functions. This study conducts a bibliometric and visualization-based analysis of circRNA-related research in diseases, aiming to reveal the current status, hotspots and emerging trends within the field. Methods: Literature published between 2013 and 2022 and indexed in the Web of Science core databases was retrieved. Visualizations of publication volume, countries, authors, institutions, journals, references, and keywords were performed. Microsoft Excel (2021) was used to analyze and graph publication volume and growth trends. Additionally, CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.18) were employed to visualize the bibliographic information. Results: Between 2013 and 2022, a total of 4195 relevant articles on circRNA in the context of diseases were identified. These articles covered 56 countries, 2528 institutions, 19,842 authors and 698 journals, citing 85,541 references. The annual publication volume showed an exponential growth trend, with rapid development post-2017. China, the United States and Germany emerged as the top three contributors, demonstrating high publication volume and total citations. Notably, Nanjing Medical University exhibited the highest publication volume, boasting 291 articles. Burton B. Yang and Li Yang consistently ranked among the top 10 authors in terms of publication volume and citations, emerging as core contributors in this research field. The journal Bioengineered ranked first in terms of published articles (160), with an impact factor of 6.832, while Molecular Cancer garnered the highest impact factor (41.4), solidifying its position as a top journal in this field. Furthermore, high-frequency keywords included "expression" "proliferation" "biomarker" "microRNA" "cancer", signifying the prevailing research hotspots and principal themes of this field over the past decade. As of 2022, "biomarker", "prostate cancer","drug resistance","papillary thyroid carcinoma", etc. continued as keywords during the outbreak period. At present, the value of circRNA application is mainly reflected in the two aspects of biomarkers and therapeutic targets, and the prediction of accurate diagnosis and precise treatment based on big data analysis, especially in cancer, will become a hot spot of research in the future. Conclusion: The trajectory of circRNA research from its biological origins to its applications in diseases has been delineated from 2013 to 2022. However, the transition to disease-specific applications and exploration of biological functions warrants further attention in future research endeavors.

14.
Food Chem ; 452: 139544, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723571

RESUMO

This study investigated the effects of high hydrostatic pressure (HHP) on the binding interactions of cyanindin-3-O-glucoside (C3G) to bovine serum albumin, human serum albumin (HSA), bovine lactoferrin, and ovotransferrin. Fluorescence quenching revealed that HHP reduced C3G-binding affinity to HSA, while having a largely unaffected role for the other proteins. Notably, pretreating HSA at 500 MPa significantly increased its dissociation constant with C3G from 24.7 to 34.3 µM. Spectroscopic techniques suggested that HSA underwent relatively pronounced tertiary structural alterations after HHP treatments. The C3G-HSA binding mechanisms under pressure were further analyzed through molecular dynamics simulation. The localized structural changes in HSA under pressure might weaken its interaction with C3G, particularly polar interactions such as hydrogen bonds and electrostatic forces, consequently leading to a decreased binding affinity. Overall, the importance of pressure-induced structural alterations in proteins influencing their binding with anthocyanins was highlighted, contributing to optimizing HHP processing for anthocyanin-based products.


Assuntos
Antocianinas , Pressão Hidrostática , Ligação Proteica , Antocianinas/química , Antocianinas/metabolismo , Humanos , Animais , Bovinos , Albumina Sérica/química , Albumina Sérica/metabolismo , Simulação de Dinâmica Molecular
15.
Environ Pollut ; 352: 124022, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38679130

RESUMO

The health risks associated with combined exposure to microplastics (MPs) and cyanobacteria toxins have gained increasing attention due to the large-scale prevalence of cyanobacterial blooms and accumulation of MPs in aquatic environments. Therefore, we explored the cardiovascular toxic effects of microcystin-LR (MC-LR, 1, 10, 100 µg/L) in the presence of 5 µm polystyrene microplastics (PS-MPs, 100 µg/L) and 80 nm polystyrene nanoplastics (PS-NPs, 100 µg/L) in zebrafish models. Embryos were exposed to certain PS-MPs and PS-NPs conditions in water between 3 h post-fertilization (hpf) and 168 hpf. Compared to MC-LR alone, a significant decrease in heart rate was observed as well as notable pericardial edema in the MC-LR + PS-MPs/NPs groups. At the same time, sinus venosus and bulbus arteriosus (SV-BA) distances were significantly increased. Furthermore, the addition of PS-MPs/NPs caused thrombosis in the caudal vein and more severe vascular damage in zebrafish larvae compared to MC-LR alone. Our findings revealed that combined exposure to PS-NPs and MC-LR could significantly decreased the expression of genes associated with cardiovascular development (myh6, nkx2.5, tnnt2a, and vegfaa), ATPase (atp1a3b, atp1b2b, atp2a1l, atp2b1a, and atp2b4), and the calcium channel (cacna1ab and ryr2a) compared to exposure to MC-LR alone. In addition, co-exposure with PS-MPs/NPs exacerbated the MC-LR-induced reactive oxygen species (ROS) production, as well as the ROS-stimulated apoptosis and heightened inflammation. We also discovered that astaxanthin (ASTA) treatment partially attenuated these cardiovascular toxic effects. Our findings confirm that exposure to MC-LR and PS-MPs/NPs affects cardiovascular development through calcium signaling interference and ROS-induced cardiovascular cell apoptosis. This study highlights the potential environmental risks of the co-existence of MC-LR and PS-MPs/NPs for fetal health, particularly cardiovascular development.


Assuntos
Embrião não Mamífero , Toxinas Marinhas , Microcistinas , Microplásticos , Estresse Oxidativo , Poliestirenos , Poluentes Químicos da Água , Peixe-Zebra , Animais , Microcistinas/toxicidade , Microplásticos/toxicidade , Toxinas Marinhas/toxicidade , Poliestirenos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
16.
Noncoding RNA Res ; 9(3): 913-920, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38638146

RESUMO

Myeloid-derived suppressor cells (MDSCs) are closely related to the occurrence and development of many cancers, but the specific mechanism is not fully understood. It has been found that N6-methyladenosine (m6A) plays a key role in RNA metabolism, but its function in MDSCs has yet to be revealed. In this study, we found that MDSCs in mice with colorectal cancer (CRC) have significantly elevated levels of m6A, while ALKBH5 expression is decreased. Overexpression of ALKBH5 can reduce the immunosuppressive function of MDSCs in vivo and in vitro, and attenuates the protumorigenic ability of MDSCs. Mechanism study found that the overexpression of ALKBH5 in MDSCs reduced the m6A modification level of Arg-1 mRNA, and then weakened the stability of Arg-1 mRNA and protein expression. These data suggest that the decreased expression of ALKBH5 in CRC tumor mice may promote the expression of Arg-1, enhance the immunosuppressor function of MDSCs, and promote tumor growth. These findings highlight that ALKBH5 may regulate the function of MDSCs in tumor-bearing mice and may be a new target for immunotherapy. This research provides a new perspective for our understanding of the role of MDSCs in cancer development, and also brings new hope for cancer treatment.

17.
Eur J Med Chem ; 270: 116358, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574638

RESUMO

The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50 = 4.46 ± 0.54 µM). Molecular docking studies revealed that 44 forms stable hydrogen bonds with amino acids around the active pocket of FABP1. Moreover, 44 alleviated the typical histological features of fatty liver in NASH mice, including steatosis, lobular inflammation, ballooning and fibrosis. Additionally, 44 has been demonstrated to have lipid metabolism regulating, anti-oxidative stress and hepatoprotective properties. This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Simulação de Acoplamento Molecular , Metabolismo dos Lipídeos , Fibrose , Proteínas de Ligação a Ácido Graxo/metabolismo , Fígado/metabolismo
18.
Plant Physiol Biochem ; 210: 108570, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38560957

RESUMO

The WUSCHEL-related homeobox (WOX) gene family is vital for plant development and stress response. In this study, we conducted a comprehensive analysis of WOX genes in Cunninghamia lanceolata (C. lanceolata) and subsequently explored the potential roles of two ClWOX genes within the WUS clade. In total, six ClWOX genes were identified through a full-length transcriptome analysis. These genes, exhibiting conserved structural and functional motifs, were assigned to the ancient clade and Modern/WUS clade, respectively, through a phylogenetic analysis. Our expression analysis indicated that these ClWOX genes were highly expressed in the middle and late developmental stages of zygotic embryos in C. lanceolata. Moreover, only ClWOX5 and ClWOX6 within the Modern/WUS clade exhibited transcriptional activity, and their expressions were also induced in response to auxin and wounding. Overexpression of ClWOX5 and ClWOX6 in Arabidopsis caused a partially sterile phenotype, resulting in a very low seed setting rate. Transcriptomic analysis revealed that expressions of many embryo-defective (EMB) genes, phytohormone-related genes, and transcription factors (TFs) were dramatically altered in ClWOX5 and ClWOX6 transgenic plants, which suggested that ClWOX5 and ClWOX6 may play specific important roles in embryo development via complex gene networks. In addition, overexpression of ClWOX5 and ClWOX6 in leaf segments promoted shoot regeneration in tobacco, indicating that ClWOX5 and ClWOX6 can promote plant regeneration and could be used to improve genetic transformation. In conclusion, these results help to elucidate the function of the WOX gene and provide a valuable basis for future studies of the developmental regulation and applications of WOX genes in C. lanceolata.


Assuntos
Cunninghamia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cunninghamia/genética , Família Multigênica , Arabidopsis/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Filogenia , Plantas Geneticamente Modificadas/genética , Genes de Plantas
19.
Lab Chip ; 24(9): 2537-2550, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38623757

RESUMO

The diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression. We introduced representative gut microbiota from individuals with depression into our constructed DoGC model, successfully recapitulating the gut microbiota structure of depressed patients. This further led to the manifestation of physiological characteristics resembling depression, such as reduced gut barrier function, chronic low-grade inflammatory responses and decreased neurotransmitter 5-HT levels. Metabolome analysis of substances in the DoGC revealed a significant increase in lipopolysaccharides and tyrosine, while hyodeoxycholic acid, L-proline and L-threonine were significantly reduced, indicating the occurrence of depression. The proposed DoGC can serve as an effective platform for studying the gut microbiota of patients with depression, providing important cues for their roles in the pathology of this condition and acting as a powerful tool for personalized medicine.


Assuntos
Depressão , Microbioma Gastrointestinal , Dispositivos Lab-On-A-Chip , Humanos , Depressão/metabolismo , Depressão/microbiologia , Técnicas de Cocultura , Técnicas Analíticas Microfluídicas/instrumentação , Células CACO-2 , Modelos Biológicos
20.
Small ; : e2400885, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616736

RESUMO

The development of pure-blue perovskite light-emitting diodes (PeLEDs) faces challenges of spectral stability and low external quantum efficiency (EQE) due to phase separation in mixed halide compositions. Perovskite quantum dots (QDs) with strong confinement effects are promising alternatives to achieve high-quality pure-blue PeLEDs, yet their performance is often hindered by the poor size distribution and high trap density. A strategy combining thermodynamic control with a polishing-driven ligand exchange process to produce high-quality QDs is developed. The strongly-confined pure-blue (≈470 nm) CsPbBr3 QDs exhibit narrow size distribution (12% dispersion) and are achieved in Br-rich ion environment based on growth thermodynamic control. Subsequent polishing-driven ligand exchange process removes imperfect surface sites and replaces initial long-chain organic ligands with short-chain benzene ligands. The resulting QDs exhibit high photoluminescence quantum yield (PLQY) to near-unity. The resulting PeLEDs exhibit a pure-blue electroluminescence (EL) emission at 472 nm with narrow full-width at half-maximum (FWHM) of 25 nm, achieving a maximum EQE of 10.7% and a bright maximum luminance of 7697 cd m-2. The pure-blue PeLEDs show ultrahigh spectral stability under high voltage, a low roll-off of EQE, and an operational half-lifetime (T50) of 127 min at an initial luminance of 103 cd m-2 under continuous operation.

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