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1.
Life Sci Alliance ; 7(10)2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111820

RESUMO

The mRNA 5'cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in the control of mRNA translation in health and disease. One mechanism of regulation of eIF4E activity is via phosphorylation of eIF4E by MNK kinases, which promotes the translation of a subset of mRNAs encoding pro-tumorigenic proteins. Work on eIF4E phosphatases has been paltry. Here, we show that PPM1G is the phosphatase that dephosphorylates eIF4E. We describe the eIF4E-binding motif in PPM1G that is similar to 4E-binding proteins (4E-BPs). We demonstrate that PPM1G inhibits cell proliferation by targeting phospho-eIF4E-dependent mRNA translation.


Assuntos
Proliferação de Células , Fator de Iniciação 4E em Eucariotos , Biossíntese de Proteínas , Proteína Fosfatase 2C , RNA Mensageiro , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Proliferação de Células/genética , Proteína Fosfatase 2C/metabolismo , Proteína Fosfatase 2C/genética , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/genética , Ligação Proteica , Células HEK293 , Animais
2.
Int Rev Cell Mol Biol ; 387: 1-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39179345

RESUMO

Epigenetics has transformed our understanding of cancer by revealing how changes in gene activity, which do not alter the DNA itself, can initiate and progress the disease. These changes include adjustments in DNA methylation, histone configuration, and non-coding RNA activity. For instance, DNA methylation can inactivate genes that typically protect against cancer, leading to broader genomic instability. Histone modifications can alter how tightly DNA is wound, influencing which genes are active or silenced; while non-coding RNAs can interfere with the messages that direct protein production, impacting cancer-related processes. Unlike genetic mutations, which are permanent and irreversible, epigenetic changes provide a malleable target for therapeutic intervention, allowing potentially reversible adjustments to gene expression patterns. This flexibility is essential in the complex landscape of cancer where static genetic solutions may be insufficient. Additionally, epigenetics bridges the gap between genetic predispositions and environmental influences on cancer, offering a comprehensive framework for understanding how lifestyle factors and external exposures impact cancer risk and progression. The integration of epigenetics into cancer research not only enhances our understanding of the disease but also opens innovative avenues for intervention that were previously unexplored in traditional genetic-focused studies. Technologies like advanced sequencing and precise epigenetic modification are paving the way for early cancer detection and more personalized treatment approaches, highlighting the critical role of epigenetics in modern cancer care.


Assuntos
Epigênese Genética , Neoplasias , Humanos , Neoplasias/genética , Animais , Metilação de DNA
4.
Int J Mol Sci ; 25(15)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39126025

RESUMO

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention.


Assuntos
Neoplasias da Mama , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Transcriptoma , Biomarcadores Tumorais/genética , Prognóstico
5.
BMC Public Health ; 24(1): 1817, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978061

RESUMO

BACKGROUND: The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated. METHODS: For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999-2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality. RESULTS: The study population was divided into young (< 60 years, N = 8,258) and old (≥ 60 years, N = 4,363) groups. The median follow-up time was 203 months. In both young and old group, sedentary lifestyle combined with even minimal AU were associated with elevated risk of death (all P < 0.05). In young group, the integration of high volume AU with any degree of PA, including sedentary PA (HR = 2.35, 95% CI 1.24-4.44, P = 0.009), low PA (HR = 1.64, 95% CI 1.01-2.68, P = 0.047), and moderate-to-vigorous PA (HR = 1.99, 95% CI 1.03-3.84, P = 0.041), was associated with an increased risk of mortality. This relationship persisted as significant after adjusting for potential confounders (all P < 0.05). In old group, combining moderate-to-vigorous PA and low volume AU (HR = 0.59, 95% CI 0.37-0.94, P = 0.027) was associated with a reduction in mortality. After adjustment, the combination of moderate-to-vigorous PA and low volume AU was independently associated with favorable prognostic outcomes (all P < 0.05). CONCLUSIONS: In both age groups, combining sedentary lifestyle with even minimal AU was a risk factor for death. In young group, combining any level of PA with high volume AU was associated with increased mortality. In old group, combining moderate-to-vigorous PA with low volume AU was related to reduced mortality.


Assuntos
Consumo de Bebidas Alcoólicas , Mortalidade , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/mortalidade , Mortalidade/tendências , Idoso , Fatores Etários , Exercício Físico , Comportamento Sedentário , Modelos de Riscos Proporcionais , Adulto Jovem , Fatores de Risco , Seguimentos
6.
Biomolecules ; 14(7)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39062572

RESUMO

Osteoarthritis (OA), a chronic joint disease affecting over 500 million individuals globally, is characterized by the destruction of articular cartilage and joint inflammation. Conventional treatments are insufficient for repairing damaged joint tissue, necessitating novel therapeutic approaches. Mesenchymal stem cells (MSCs), with their potential for differentiation and self-renewal, hold great promise as a treatment for OA. However, challenges such as MSC viability and apoptosis in the ischemic joint environment hinder their therapeutic effectiveness. Hydrogels with biocompatibility and degradability offer a three-dimensional scaffold that support cell viability and differentiation, making them ideal for MSC delivery in OA treatment. This review discusses the pathological features of OA, the properties of MSCs, the challenges associated with MSC therapy, and methods for hydrogel preparation and functionalization. Furthermore, it highlights the advantages of hydrogel-based MSC delivery systems while providing insights into future research directions and the clinical potential of this approach.


Assuntos
Hidrogéis , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite , Humanos , Osteoartrite/terapia , Osteoartrite/patologia , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Diferenciação Celular , Cartilagem Articular/patologia
7.
Support Care Cancer ; 32(7): 484, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958768

RESUMO

PURPOSE: This article provided a comprehensive scoping review, synthesizing existing literature on the financial distress faced by breast cancer patients. It examined the factors contributing to financial distress, the impact on patients, coping mechanisms employed, and potential alleviation methods. The goal was to organize existing evidence and highlight possible directions for future research. METHODS: We followed the scoping review framework proposed by the Joanna Briggs Institute (JBI) to synthesize and report evidence. We searched electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, for relevant literature. We included English articles that met the following criteria: (a) the research topic was financial distress or financial toxicity, (b) the research subjects were adult breast cancer patients, and (c) the article type was quantitative, qualitative, or mixed-methods research. We then extracted and integrated relevant information for reporting. RESULTS: After removing duplicates, 5459 articles were retrieved, and 43 articles were included based on the inclusion and exclusion criteria. The articles addressed four main themes related to financial distress: factors associated with financial distress, impact on breast cancer patients, coping mechanisms, and potential methods for alleviation. The impact of financial distress on patients was observed in six dimensions: financial expenses, financial resources, social-psychological reactions, support seeking, coping care, and coping lifestyle. While some studies reported potential methods for alleviation, few discussed the feasibility of these solutions. CONCLUSIONS: Breast cancer patients experience significant financial distress with multidimensional impacts. Comprehensive consideration of possible confounding factors is essential when measuring financial distress. Future research should focus on exploring and validating methods to alleviate or resolve this issue.


Assuntos
Adaptação Psicológica , Neoplasias da Mama , Estresse Financeiro , Humanos , Neoplasias da Mama/psicologia , Neoplasias da Mama/economia , Estresse Financeiro/psicologia , Feminino , Efeitos Psicossociais da Doença
8.
Int J Ophthalmol ; 17(7): 1273-1282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026905

RESUMO

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

9.
ACS Appl Mater Interfaces ; 16(30): 39021-39034, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39033517

RESUMO

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and ß-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.


Assuntos
Naftoquinonas , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Animais , Camundongos , Naftoquinonas/química , Naftoquinonas/farmacologia , Linhagem Celular Tumoral , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Peróxido de Hidrogênio/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Estresse Oxidativo/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Glutationa/metabolismo , Glutationa/química , Sistemas de Liberação de Medicamentos
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124758, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38963945

RESUMO

In this study, electroporation-surface-enhanced Raman scattering (SERS) was applied to rapidly measure intracellular pH. The generation of a sensitive SERS probe for measuring pH in the range of 6.0-8.0 was accomplished through the conjugation of the pH-sensitive molecule 4-mercaptobenzoic acid (4-MBA) to the surface of gold nanoparticles (Au NPs) through its thiol functional group. This bioprobe was then rapidly introduced into nasopharyngeal carcinoma CNE-1 cells by electroporation, followed by SERS scanning and the fitting of intensity ratios of each detection point's Raman peaks at 1423 cm-1 and 1072 cm-1, to create the pH distribution map of CNE-1 cells. The electroporation-SERS assay introduces pH bioprobes into a living cell in a very short time and disperses the nanoprobe throughout the cytoplasm, ultimately enabling rapid and comprehensive pH analysis of the entire cell. Our work demonstrates the potential of electroporation-SERS for the biochemical analysis of live cells.


Assuntos
Eletroporação , Ouro , Nanopartículas Metálicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Concentração de Íons de Hidrogênio , Eletroporação/métodos , Humanos , Ouro/química , Nanopartículas Metálicas/química , Linhagem Celular Tumoral , Compostos de Sulfidrila/química , Compostos de Sulfidrila/análise , Benzoatos/química
11.
Fitoterapia ; 177: 106108, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38964561

RESUMO

BACKGROUND: In Chinese Pharmacopeia, Picrasma quassioides (PQ) stems and leaves are recorded as Kumu with antimicrobial, anti-cancer, anti-parasitic effects, etc. However, thick stems are predominantly utilized as medicine in many Asian countries, with leaves rarely used. By now, the phytochemistry and bioactivity of PQ leaves are not well investigated. METHODS: An Orbitrap Elite mass spectrometer was employed to comprehensively investigate PQ stems and leaves sourced from 7 different locations. Additionally, their bioactivities were evaluated against 5 fungi, 6 Gram-positive bacteria and 9 Gram-negative bacteria, a tumor cell line (A549), a non-tumor cell line (WI-26 VA4) and N2 wild-type Caenorhabditis elegans. RESULTS: Bioassay results demonstrated the efficacy of both leaves and stems against tumor cells, several bacteria and fungi, while only leaves exhibited anthelmintic activity against C. elegans. A total of 181 compounds were identified from PQ stems and leaves, including 43 ß-carbolines, 20 bis ß-carbolines, 8 canthinone alkaloids, 56 quassinoids, 12 triterpenoids, 13 terpenoid derivatives, 11 flavonoids, 7 coumarins, and 11 phenolic derivatives, from which 10 compounds were identified as indicator components for quality evaluation. Most alkaloids and triterpenoids were concentrated in PQ stems, while leaves exhibited higher levels of quassinoids and other carbohydrate (CHO) components. CONCLUSION: PQ leaves exhibit distinct chemical profiles and bioactivity with the stems, suggesting their suitability for medicinal purposes. So far, the antibacterial, antifungal, and anthelmintic activities of PQ leaves were first reported here, and considering PQ sustainability, the abundant leaves are recommended for increased utilization, particularly for their rich content of PQ quassinoids.


Assuntos
Caenorhabditis elegans , Compostos Fitoquímicos , Picrasma , Folhas de Planta , Caules de Planta , Folhas de Planta/química , Picrasma/química , Animais , Caules de Planta/química , Caenorhabditis elegans/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Estrutura Molecular , Antineoplásicos Fitogênicos/farmacologia , Alcaloides/farmacologia , Quassinas/farmacologia , Quassinas/química , Quassinas/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Helmínticos/química , Fungos/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/análise
12.
Pharmaceutics ; 16(7)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39065602

RESUMO

Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness of chemotherapy. This system delivers nano-sized dasatinib and atovaquone specifically to liver tumor sites and facilitates intra-tumoral permeation upon release. Through JC-1, immunohistochemistry, and DNA damage analyses, the therapeutic effect of DASA+ATO@PLT was assessed. In vitro simulation and intravital imaging were carried out to determine the accumulation of dasatinib and atovaquone in liver tumor sites. The experiment demonstrated the accumulation of dasatinib and atovaquone in tumor sites, followed by deep permeation in the tumor microenvironment with the assistance of PLTs, while simultaneously revealing the ability of DASA+ATO@PLT to remodel the liver cancer microenvironment (overcoming hypoxia) and enhance chemotherapeutic efficacy. This system utilizes the natural tumor recognition ability of PLTs and enhances the chemo-immunotherapeutic effect through targeted delivery of nano-chemotherapeutic drugs to the tumor, resulting in effective accumulation and infiltration. The PLT-mediated nanodrug delivery system serves as a "Trojan horse" to carry therapeutic drugs as cargo and deliver them to target cells, leading to favorable outcomes.

13.
Cancer Biol Med ; 21(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825813

RESUMO

In exploring persistent infections and malignancies, a distinctive subgroup of CD8+ T cells, progenitor exhausted CD8+ T (Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8+ T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.


Assuntos
Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia/métodos , Linfócitos T CD8-Positivos/imunologia , Animais , Microambiente Tumoral/imunologia
14.
Int Immunopharmacol ; 137: 112289, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38889505

RESUMO

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) primarily expressed in hematopoietic stem cells and dendritic cells (DCs). While FLT3 plays a critical role in the proliferation, development and maintenance of DCs, thus influencing immune responses under both normal and pathological conditions, there also exists some evidence that FLT3+DC may be involved with immune responses in liver transplantation (LT). In this study, results from single-cell sequencing data analysis revealed a clear relationship between FLT3+DCs and Regulatory T cells (Tregs) in liver tissue of LT recipients. In peripheral blood samples of LT patients, levels of FLT3+DCs were decreased post-LT-surgery, while Tregs were increased. In a LT mouse model, levels of FLT3+DCs in the liver and bone marrow exhibited an initial time-dependent decrease followed by an increase after LT surgery. Results as obtained with co-culture experiments using mature BMDCs and CD4+ T cells revealed fluctuations in Tregs in response to FLT3 inhibitors and the FLT3 ligand. These findings suggest that FLT3+DCs could emerge as a novel target for mitigating immune rejection in LT.


Assuntos
Células Dendríticas , Rejeição de Enxerto , Transplante de Fígado , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Tirosina Quinase 3 Semelhante a fms , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Masculino , Camundongos , Fígado/imunologia , Feminino , Técnicas de Cocultura , Pessoa de Meia-Idade , Células Cultivadas , Camundongos Endogâmicos BALB C , Proteínas de Membrana
15.
Phytother Res ; 38(7): 3782-3800, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38839050

RESUMO

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.


Assuntos
Enteropatias , Polifenóis , Humanos , Polifenóis/farmacologia , Criança , Enteropatias/tratamento farmacológico , Enteropatias/dietoterapia , Enteropatias/prevenção & controle , Antioxidantes/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Dieta
16.
Sheng Li Xue Bao ; 76(3): 429-437, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38939937

RESUMO

As a multifunctional adipokine, chemerin plays a crucial role in various pathophysiological processes through endocrine and paracrine manner. It can bind to three known receptors (ChemR23, GPR1 and CCRL2) and participate in energy metabolism, glucose and lipid metabolism, and inflammation, especially in metabolic diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, which seriously affects the normal life of women of childbearing age. Patients with PCOS have significantly increased serum levels of chemerin and high expression of chemerin in their ovaries. More and more studies have shown that chemerin is involved in the occurrence and development of PCOS by affecting obesity, insulin resistance, hyperandrogenism, oxidative stress and inflammatory response. This article mainly reviews the production, subtypes, function and receptors of chemerin protein, summarizes and discusses the research status of chemerin protein in PCOS from the perspectives of metabolism, reproduction and inflammation, and provides theoretical basis and reference for the clinical diagnosis and treatment of PCOS.


Assuntos
Quimiocinas , Peptídeos e Proteínas de Sinalização Intercelular , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/metabolismo , Humanos , Quimiocinas/metabolismo , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores de Quimiocinas/metabolismo , Resistência à Insulina , Animais , Receptores Acoplados a Proteínas G/metabolismo , Fatores Quimiotáticos/metabolismo
17.
Fish Shellfish Immunol ; 151: 109691, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38871138

RESUMO

Viral hemorrhagic septicemia virus (VHSV) poses a significant threat to the aquaculture industry, prompting the need for effective preventive measures. Here, we developed an inactivated VHSV and revealed the molecular mechanisms underlying the host's protective response against VHSV. The vaccine was created by treating VHSV with 0.05 % formalin at 16 °C for 48 h, which was determined to be the most effective inactivation method. Compared with nonvaccinated fish, vaccinated fish exhibited a remarkable increase in survival rate (99 %) and elevated levels of serum neutralizing antibodies, indicating strong immunization. To investigate the gene changes induced by vaccination, RNA sequencing was performed on spleen samples from control and vaccinated fish 14 days after vaccination. The analysis revealed 893 differentially expressed genes (DEGs), with notable up-regulation of immune-related genes such as annexin A1a, coxsackievirus and adenovirus receptor homolog, V-set domain-containing T-cell activation inhibitor 1-like, and heat shock protein 90 alpha class A member 1 tandem duplicate 2, indicating a vigorous innate immune response. Furthermore, KEGG enrichment analysis highlighted significant enrichment of DEGs in processes related to antigen processing and presentation, necroptosis, and viral carcinogenesis. GO enrichment analysis further revealed enrichment of DEGs related to the regulation of type I interferon (IFN) production, type I IFN production, and negative regulation of viral processes. Moreover, protein-protein interaction network analysis identified central hub genes, including IRF3 and HSP90AA1.2, suggesting their crucial roles in coordinating the immune response elicited by the vaccine. These findings not only confirm the effectiveness of our vaccine formulation but also offer valuable insights into the underlying immunological mechanisms, which can be valuable for future vaccine development and disease management in the aquaculture industry.


Assuntos
Bass , Doenças dos Peixes , Septicemia Hemorrágica Viral , Novirhabdovirus , Vacinas de Produtos Inativados , Vacinas Virais , Animais , Novirhabdovirus/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Septicemia Hemorrágica Viral/prevenção & controle , Septicemia Hemorrágica Viral/imunologia , Bass/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Imunidade Inata , Genótipo , Vacinação/veterinária , Imunização/veterinária
18.
Mol Cancer ; 23(1): 122, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844984

RESUMO

Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.


Assuntos
Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Epigênese Genética , Terapia de Alvo Molecular , Transição Epitelial-Mesenquimal
19.
J Robot Surg ; 18(1): 248, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856862

RESUMO

The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.


Assuntos
Tempo de Internação , Obesidade , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Obesidade/complicações , Neoplasias da Próstata/cirurgia , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Laparoscopia/métodos , Duração da Cirurgia , Transfusão de Sangue/estatística & dados numéricos
20.
J Robot Surg ; 18(1): 261, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904929

RESUMO

This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.


Assuntos
Períneo , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Períneo/cirurgia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Incontinência Urinária/etiologia , Complicações Pós-Operatórias/etiologia
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