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1.
Quant Imaging Med Surg ; 14(5): 3489-3500, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38720866

RESUMO

Background: Hypoxia is the bottleneck that affects the response of conventional photon radiotherapy, but it does not seem to have much effect on carbon ion radiotherapy (CIRT). This study aimed to evaluate the changes of hypoxia before and after CIRT in patients with non-small cell lung cancer (NSCLC) and whether 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) imaging could predict the response to CIRT in NSCLC patients. Methods: A total of 29 patients with NSCLC who received CIRT were retrospectively included. 18F-FMISO PET/CT imaging was performed before and after treatment, and chest CT was performed after radiotherapy. Radiation response within 1 week after radiotherapy and at the initial follow-up were defined as the immediate response (IR) and early response (ER), respectively. The tumor-to-muscle ratio (TMR), hypoxia volume (HV), and the ΔTMR and ΔHV values of 18F-FMISO uptake were collected. Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and binary logistic regression were used to analyze data. Results: (I) Baseline TMR could predict the IR to CIRT with a baseline TMR cut-off value of 2.35, an area under the curve (AUC) of 0.85 [95% confidence interval (CI): 0.62-1.00], a sensitivity of 80.0%, a specificity of 87.5%, and an accuracy of 85.7%. Taking the baseline TMR =2.35 as the cut-off value of high-hypoxia and low-hypoxia group, the IR rate of the high-hypoxia group [66.7% (4/6)] and the low-hypoxia group [6.7% (1/15)] was statistically different (P=0.01). (II) ΔTMR could predict early treatment response after CIRT at initial follow-up, with a cut-off value of ΔTMR =36.6%, AUC of 0.80 (95% CI: 0.61-1.00), sensitivity of 72.7%, specificity of 90.0% and accuracy of 71.4%. Conclusions: A higher degree of tumor hypoxia may be associated with a better IR to CIRT. ΔTMR could predict early treatment response after CIRT.

2.
Mol Neurobiol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767836

RESUMO

Duchenne muscular dystrophy (DMD), a lethal X-linked recessive genetic disease, is characterized by progressive muscle wasting which will lead to premature death by cardiorespiratory complications in their late twenties. And 2.5-19% DMD carriers that also suffer from skeletal muscle damage or dilated cardiomyopathy when diagnosed as soon as possible is meaningful for prenatal diagnosis and advance warning for self-health. The current DMD carrier screening mainly relies on detecting serum creatine kinase activity, covering only 50-70% DMD carriers which will cause many false negatives and require the discovery of highly effective biomarker and simple detection procedure for DMD carriers. In this article, we have compiled a comprehensive summary of all documented biomarkers associated with DMD and categorized them based on their expression patterns. We specifically pinpointed novel DMD biomarkers, previously unreported in DMD carriers, and conducted further investigations to explore their potential. Compared to creatine kinase activity alone in DMD carriers, creatine kinase-MM can improve the specificity from 73 to 81%. And our investigation revealed another promising protein: proto-oncogene tyrosine-protein kinase receptor (RET). When combined with creatine kinase-MM (creatine kinase-MM/RET ratio), it significantly enhances the specificity (from 81 to 83%) and sensitivity (from 71.4 to 93%) of detecting DMD carriers in serum. Moreover, we successfully devised an efficient method for extracting RET from dried blood spots. This breakthrough allowed us to detect both creatine kinase-MM and RET using dried blood spots without compromising the detection rate.

3.
Cell Commun Signal ; 22(1): 280, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773448

RESUMO

INTRODUCTION: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV- and HBV+ HCC have remained unchanged, limiting HCC treatment options. OBJECTIVES: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. METHODS: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. RESULTS: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. CONCLUSION: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Serina-Treonina Quinases TOR , Humanos , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Serina-Treonina Quinases TOR/metabolismo , Vírus da Hepatite B/fisiologia , Metabolismo dos Lipídeos , Masculino , Lipídeos/sangue , Transdução de Sinais , Sistema de Sinalização das MAP Quinases , Hepatite B/complicações , Hepatite B/virologia , Hepatite B/metabolismo , Pessoa de Meia-Idade , Feminino
4.
Biomaterials ; 309: 122615, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38759486

RESUMO

Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.

5.
Reprod Biol Endocrinol ; 22(1): 46, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637876

RESUMO

BACKGROUND: Metformin is an insulin sensitizer that is widely used for the treatment of insulin resistance in polycystic ovary syndrome patients. However, metformin can cause gastrointestinal side effects. PURPOSE: This study showed that the effects of quercetin are comparable to those of metformin. Therefore, this study aimed to systematically evaluate the efficacy of quercetin in treating PCOS. METHODS: The present systematic search of the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data Information Site, Chinese Scientific Journals Database (VIP), SinoMed, Web of Science, and PubMed databases was performed from inception until February 2024. The methodological quality was then assessed by SYRCLE's risk of bias tool, and the data were analyzed by RevMan 5.3 software. RESULTS: Ten studies were included in the meta-analysis. Compared with those in the model group, quercetin in the PCOS group had significant effects on reducing fasting insulin serum (FIS) levels (P = 0.0004), fasting blood glucose (FBG) levels (P = 0.01), HOMA-IR levels (P < 0.00001), cholesterol levels (P < 0.0001), triglyceride levels (P = 0.001), testosterone (T) levels (P < 0.00001), luteinizing hormone (LH) levels (P = 0.0003), the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (P = 0.01), vascular endothelial growth factor (VEGF) levels (P < 0.00001), malondialdehyde (MDA) levels (P = 0.03), superoxide dismutase (SOD) levels (P = 0.01) and GLUT4 mRNA expression (P < 0.00001). CONCLUSION: This meta-analysis suggested that quercetin has positive effects on PCOS treatment. Quercetin can systematically reduce insulin, blood glucose, cholesterol, and triglyceride levels in metabolic pathways. In the endocrine pathway, quercetin can regulate the function of the pituitary-ovarian axis, reduce testosterone and luteinizing hormone (LH) levels, and lower the ratio of LH to follicle-stimulating hormone (FSH). Quercetin can regulate the expression of the GLUT4 gene and has antioxidative effects at the molecular level.


Assuntos
Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Feminino , Animais , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Glicemia , Fator A de Crescimento do Endotélio Vascular , Hormônio Luteinizante , Insulina , Hormônio Foliculoestimulante , Metformina/uso terapêutico , Testosterona , Colesterol , Triglicerídeos
7.
ACS Appl Mater Interfaces ; 16(17): 21546-21556, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626342

RESUMO

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.


Assuntos
Microambiente Tumoral , Animais , Camundongos , Humanos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Oxigênio/química , Compostos de Tungstênio/química , Compostos de Tungstênio/farmacologia , Linhagem Celular Tumoral
8.
Clin Chim Acta ; 557: 117889, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38531466

RESUMO

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.


Assuntos
Doença de Fabry , Humanos , Recém-Nascido , Feminino , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Estudos Retrospectivos , Triagem Neonatal/métodos , Mutação , Testes Genéticos , alfa-Galactosidase/genética , China
9.
Sci Total Environ ; 926: 171809, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513845

RESUMO

Soil cadmium (Cd) can affect crop growth and food safety, and through the enrichment in the food chain, it ultimately poses a risk to human health. Reducing the re-mobilization of Cd caused by the release of protons and acids by crops and microorganisms after stabilization is one of the significant technical challenges in agricultural activities. This study aimed to investigate the re-mobilization of stabilized Cd within the clay mineral-bound fraction of soil and its subsequent accumulation in crops utilizing nitrogen ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N), at 60 and 120 mg kg-1. Furthermore, the study harvested root exudates at various growth stages to assess their direct influence on the re-mobilization of stabilized Cd and to evaluate the indirect effects mediated by soil microorganisms. The results revealed that, in contrast to the NO3--N treatment, the NH4+-N treatment significantly enhanced the conversion of clay mineral-bound Cd in the soil to NH4NO3-extractable Cd. It also amplified the accumulation of Cd in edible amaranth, with concentrations in roots and shoots rising from 1.7-6.0 mg kg-1 to 4.3-9.8 mg kg-1. The introduction of NH4+-N caused a decrease in the pH value of the rhizosphere soil and stimulated the production and secretion organic and amino acids, such as oxalic acid, lactic acid, stearic acid, succinic acid, and l-serine, from the crop roots. Furthermore, compared to NO3--N, the combined interaction of root exudates with NH4+-N has a more pronounced impact on the abundance of microbial genes associated with glycolysis pathway and tricarboxylic acid cycle, such as pkfA, pfkB, sucB, sucC, and sucD. The effects of NH4+-N on crops and microorganisms ultimately result in a significant increase in the re-mobilization of stabilized Cd. However, the simulated experiments showed that microorganisms only contribute to 3.8-6.6 % of the re-mobilization of clay mineral-bound Cd in soil. Therefore, the fundamental strategy to inhibit the re-mobilization of stabilized Cd in vegetable cultivation involves the regulation of proton and organic acid secretion by crops.


Assuntos
Poluentes do Solo , Solo , Humanos , Solo/química , Cádmio/análise , Argila , Nitrogênio/metabolismo , Compostos Orgânicos/metabolismo , Produtos Agrícolas/metabolismo , Minerais/metabolismo , Fertilização , Poluentes do Solo/análise
10.
Fish Shellfish Immunol ; 148: 109494, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499217

RESUMO

Vibrio harveyi poses a significant threat to fish and invertebrates in mariculture, resulting in substantial financial repercussions for the aquaculture sector. Valine-glycine repeat protein G (VgrG) is essential for the type VI secretion system's (T6SS) assembly and secretion. VgrG from V. harveyi QT520 was cloned and analyzed in this study. The localization of VgrG was determined by Western blot, which revealed that it was located in the cytoplasm, secreted extracellularly, and attached to the membrane. The effectiveness of two vaccinations against V. harveyi infection-a subunit vaccine (rVgrG) and a DNA vaccine (pCNVgrG) prepared with VgrG was evaluated. The findings indicated that both vaccines provided a degree of protection against V. harveyi challenge. At 4 weeks post-vaccination (p.v.), the rVgrG and pCNVgrG exhibited relative percent survival rates (RPS) of 71.43% and 76.19%, respectively. At 8 weeks p.v., the RPS for rVgrG and pCNVgrG were 68.21% and 72.71%, respectively. While both rVgrG and pCNVgrG elicited serum antibody production, the subunit vaccinated fish demonstrated significantly higher levels of serum anti-VgrG specific antibodies than the DNA vaccine group. The result of qRT-PCR demonstrated that the expression of major histocompatibility complex (MHC) class Iα, tumor necrosis factor-alpha (TNF-α), interferon γ (IFNγ), and cluster of differentiation 4 (CD4) were up-regulated by both rVgrG and pCNVgrG. Fish vaccinated with rVgrG and pCNVgrG exhibited increased activity of acid phosphatase, alkaline phosphatase, superoxide dismutase, and lysozyme. These findings suggest that VgrG from V. harveyi holds potential for application in vaccination.


Assuntos
Doenças dos Peixes , Vacinas de DNA , Vibrioses , Vibrio , Animais , Vibrioses/prevenção & controle , Vibrioses/veterinária , Valina , Vacinas Bacterianas , Peixes , Doenças dos Peixes/prevenção & controle
11.
ACS Appl Mater Interfaces ; 16(13): 15916-15930, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38416419

RESUMO

Photodynamic therapy's antitumor efficacy is hindered by the inefficient generation of reactive oxygen species (ROS) due to the photogenerated electron-hole pairs recombination of photosensitizers (PS). Therefore, there is an urgent need to develop efficient PSs with enhanced carrier dynamics. Herein, we designed Schottky junctions composed of cobalt tetroxide and palladium nanocubes (Co3O4@Pd) with a built-in electric field as effective PS. The built-in electric field enhanced photogenerated charge separation and migration, resulting in the generation of abundant electron-hole pairs and allowing effective production of ROS. Thanks to the built-in electric field, the photocurrent intensity and carrier lifetime of Co3O4@Pd were approximately 2 and 3 times those of Co3O4, respectively. Besides, the signal intensity of hydroxyl radical and singlet oxygen increased to 253.4% and 135.9%, respectively. Moreover, the localized surface plasmon resonance effect of Pd also enhanced the photothermal conversion efficiency of Co3O4@Pd to 40.50%. In vitro cellular level and in vivo xenograft model evaluations demonstrated that Co3O4@Pd could generate large amounts of ROS, trigger apoptosis, and inhibit tumor growth under near-infrared laser irradiation. Generally, this study reveals the contribution of the built-in electric field to improving photodynamic performance and provides new ideas for designing efficient inorganic PSs.


Assuntos
Cobalto , Neoplasias , Óxidos , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Neoplasias/tratamento farmacológico , Raios Infravermelhos
12.
J Craniofac Surg ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38330493

RESUMO

Forearm skin flaps are widely used to reconstruct oral cancer due to their advantages, such as vascular stability, simple preparation, and a high success rate. However, traditional forearm skin flaps have shortcomings: the donor site requires grafting, which increases surgical trauma by creating a second surgical area, and the scarring at the donor site significantly affects the esthetics of the forearm. Therefore, we have designed a new ^-shaped radial forearm skin flap, in which the flap is designed as 2 semi-elliptical subunits. After the flap is harvested, these 2 subunits are joined, and the reserved skin at the donor site is directly sutured to the outer part of the donor site. The area of the ^-shaped radial forearm skin flap can be as large as that prepared with traditional forearm skin flaps, and there is no need for grafting at the donor site. This avoids additional trauma to the donor site after surgery, significantly reduces related complications, and enhances the esthetic outcome. This paper reports a case of a cheek cancer (carcinoma of the buccal mucosa) patient (T3N0M0), where the flap survived postoperatively, and both the surgical site and donor site healed in the first phase. The patient has no sensory or functional impairments; swallowing and speech functions are satisfactory.

13.
Ann Nucl Med ; 38(5): 360-368, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38407800

RESUMO

OBJECTIVE: In this study, the uptake characteristics of [18F]fibroblast activation protein inhibitor (FAPI) molecular imaging probe were investigated in acute radiation pneumonia and lung cancer xenografted mice before and after radiation to assess the future applicability of [18F]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response. METHODS: Initially, the biodistribution of [18F]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [18F]FAPI and [18F]fluorodeoxyglucose (FDG) PET/CT imaging efficacy in normal ICR, LLC tumor-bearing mice was evaluated. A radiation pneumonia model was then investigated using a gamma counter, small animal PET/CT, and autoradiography. The uptake properties of [18F]FAPI in lung cancer and acute radiation pneumonia were investigated using autoradiography and PET/CT imaging in mice. RESULTS: The tumor area was visible in [18F]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [18F]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [18F]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-ɑ decreased after thorax irradiation. Correspondingly, there was no notable [18F]FAPI uptake after irradiation, but there was an increase of [18F]FDG uptake in malignancies and lungs. CONCLUSIONS: The background uptake of [18F]FAPI is negligible. Moreover, the uptake of [18F]FAPI may not be affected by acute radiation pneumonitis compared to [18F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.


Assuntos
Neoplasias Pulmonares , Quinolinas , Pneumonite por Radiação , Animais , Camundongos , Camundongos Endogâmicos ICR , Pneumonite por Radiação/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Modelos Animais de Doenças , Radioisótopos de Gálio
14.
Am J Cancer Res ; 14(1): 130-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323291

RESUMO

Circular RNAs (circRNAs) have been extensively studied for their critical roles as noncoding RNAs (ncRNAs) in gastric cancer (GC). In this study, we focused on the expression, function and molecular mechanism of circRNA_0023685 in gastric cancer (GC) to provide new ways for the diagnosis and treatment of GC. Firstly, a novel differentially expressed circRNA, circRNA_0023685, was identified, and its differential expression in GC plasma, tissue, and cell lines was further verified by RT-qPCR. Next, circRNA_0023685 was verified to promote the proliferation, migration and apoptosis of GC cells in vitro. CircRNA_0023685 was also proved to enhance the growth of GC tumors in xenograft models. Finally, for excavating the mechanism to promote GC, downstream microRNAs (miRNAs) and mRNAs were screened by bioinformatics analyses. After intersecting the target genes and genes enriched in GO analysis, a circRNA competing endogenous RNAs (ceRNAs) network was built. A protein-protein interaction (PPI) network was then constructed to find the candidate gene, APP. Our study confirmed that the highly expressed circRNA_0023685 could promote GC, which provided a new clinical diagnostic biomarker and therapeutic target for GC.

15.
Cancer Med ; 13(2): e6950, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38379323

RESUMO

BACKGROUND AND PURPOSE: As an advanced radiotherapy technique, carbon ion radiotherapy has demonstrated good efficacy and low toxicity for prostate cancer patients, but the radiobiological mechanism of killing tumor cells has not been fully elucidated. This study aims to explore the antitumor effects of carbon ion irradiation (CIR) through investigating the immune response induced by CIR in prostate cancer-bearing mice and the underlying molecular mechanism. MATERIALS AND METHODS: We established subcutaneous transplantation tumor models of prostate cancer to evaluate the tumor inhibition effect of CIR. Investigation of immunophenotype alterations were assessed by flow cytometry. Immunofluorescence, western blot, and real-time quantitative PCR was employed to analyze the activation of cGAS-STING pathway. RESULTS: CIR showed more powerful tumor growth control than photon irradiation in immunocompetent syngeneic C57BL/6 mice. CIR exerts antitumor effect by triggering immune response, characterized by increased CD4+ T cells and macrophages in tumor, enhanced CD8+ T cells and T effector memory cells in spleen, improved IFN-γ production of CD8+ tumor-infiltrating lymphocytes, and reduced exhausted T cells in tumor and spleen. Additionally, production of cytoplasmic double-stranded DNA, protein levels of p-TBK1 and p-IRF3 in the cGAS-STING pathway, and gene expression levels of downstream interferon-stimulated genes were significantly increased after CIR in a dose-dependent manner. Treatment of RM1 tumor-bearing mice with the STING inhibitor C-176 impaired the antitumor effect of CIR. CONCLUSION: The excellent antitumor activity of CIR in immunocompetent prostate cancer-bearing C57BL/6 mice may be attributed to stronger induction of antitumor immune response and higher activation of cGAS-STING pathway.


Assuntos
Radioterapia com Íons Pesados , Neoplasias da Próstata , Humanos , Masculino , Camundongos , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Linfócitos T CD8-Positivos/metabolismo , Camundongos Endogâmicos C57BL , Nucleotidiltransferases/genética , Imunidade , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Carbono
16.
J Ethnopharmacol ; 326: 117867, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38342155

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.


Assuntos
Interleucina-17 , Psoríase , Animais , Camundongos , Imiquimode , Interleucina-17/genética , Interleucina-17/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Imunidade Inata , Interleucina-6/metabolismo , Linfócitos/metabolismo , Pele , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Citocinas/metabolismo , Interleucina-23/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
17.
Fish Physiol Biochem ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411877

RESUMO

Herbs and their by-products are important traditional medicines and food supplements; they provide numerous beneficial effects for animals. Consequently, probiotics are living cell organisms, nontoxic, and friendly microbes. Probiotics have numerous beneficial activities such as inhibition of pathogens, enhancement of the immune system, growth, disease resistance, improving water quality, reducing toxic effects, synthesis of vitamins, prevention of cancer, reduction of irritable bowel syndrome, and more positive responses in animals. Herbal and probiotic combinations have more active responses and produce new substances to enhance beneficial responses in animals. Herbal and probiotic mixture report is still limited applications for animals. However, the mechanisms by which they interact with the immune system and gut microbiota in animals are largely unclear. This review provides some information on the effect of herbal and probiotic blend on animals. This review discusses current research advancements to fulfill research gaps and promote effective and healthy animal production.

18.
Fish Physiol Biochem ; 50(2): 635-651, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165563

RESUMO

Largemouth bass (Micropterus salmoides) were fed with three diets containing 6%, 12%, and 18% wheat starch for 70 days to examine their impacts on growth performance, glucose and lipid metabolisms, and liver and intestinal health. The results suggested that the 18% starch group inhibited the growth, and improved the hepatic glycogen content compared with the 6% and 12% starch groups (P < 0.05). High starch significantly improved the activities of glycolysis-related enzymes, hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), and pyruvate kinase (PK) (P < 0.05); promoted the mRNA expression of glycolysis-related phosphofructokinase (pfk); decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC), and phosphoenolpyruvate carboxykinase (PEPCK); and reduced the mRNA expression of gluconeogenesis-related fructose-1,6-bisphosphatase-1(fbp1) (P < 0.05). High starch reduced the hepatic mRNA expressions of bile acid metabolism-related cholesterol hydroxylase (cyp7a1) and small heterodimer partner (shp) (P < 0.05), increased the activity of hepatic fatty acid synthase (FAS) (P < 0.05), and reduced the hepatic mRNA expressions of lipid metabolism-related peroxisome proliferator-activated receptor α (ppar-α) and carnitine palmitoyltransferase 1α (cpt-1α) (P < 0.05). High starch promoted inflammation; significantly reduced the mRNA expressions of anti-inflammatory cytokines transforming growth factor-ß1 (tgf-ß1), interleukin-10 (il-10), and interleukin-11ß (il-11ß); and increased the mRNA expressions of pro-inflammatory cytokine tumor necrosis factor-α (tnf-α), interleukin-1ß (il-1ß), and interleukin-8 (il-8) in the liver and intestinal tract (P < 0.05). Additionally, high starch negatively influenced the intestinal microbiota, with the reduced relative abundance of Trichotes and Actinobacteria and the increased relative abundance of Firmicutes and Proteobacteria. In conclusion, low dietary wheat starch level (6%) was more profitable to the growth and health of M. salmoides, while high dietary starch level (12% and 18%) could regulate the glucose and lipid metabolisms, impair the liver and intestinal health, and thus decrease the growth performance of M. salmoides.


Assuntos
Bass , Glucose , Animais , Glucose/metabolismo , Amido/farmacologia , Bass/fisiologia , Triticum/metabolismo , Metabolismo dos Lipídeos , Dieta/veterinária , Fígado/metabolismo , Carboidratos da Dieta/metabolismo , Lipídeos , Fosfofrutoquinases/metabolismo , RNA Mensageiro/metabolismo
19.
J Fish Dis ; 47(5): e13916, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38226408

RESUMO

Nanotechnology is an expanding and new technology that prompts production with nanoparticle-based (1-100 nm) organic and inorganic materials. Such a tool has an imperative function in different sectors like bioengineering, pharmaceuticals, electronics, energy, nuclear energy, and fuel, and its applications are helpful for human, animal, plant, and environmental health. In exacting, the nanoparticles are synthesized by top-down and bottom-up approaches through different techniques such as chemical, physical, and biological progress. The characterization is vital and the confirmation of nanoparticle traits is done by various instrumentation analyses like UV-Vis spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, X-ray diffraction, atomic force microscopy, annular dark-field imaging, and intracranial pressure. In addition, probiotics are friendly microbes which while administered in sufficient quantity confer health advantages to the host. Characterization investigation is much more significant to the identification of good probiotics. Similarly, haemolytic activity, acid and bile salt tolerance, autoaggregation, antimicrobial compound production, inhibition of pathogens, enhance the immune system, and more health-beneficial effects on the host. The synergistic effects of nanoparticles and probiotics combined delivery applications are still limited to food, feed, and biomedical applications. However, the mechanisms by which they interact with the immune system and gut microbiota in humans and animals are largely unclear. This review discusses current research advancements to fulfil research gaps and promote the successful improvement of human and animal health.


Assuntos
Anti-Infecciosos , Doenças dos Peixes , Nanopartículas Metálicas , Nanopartículas , Drogas Veterinárias , Humanos , Animais , Extratos Vegetais/química , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia
20.
Eur J Med Res ; 29(1): 9, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173034

RESUMO

BACKGROUND: The aim of this study was to evaluate the efficacy of fluorine 18 (18F) labeled fibroblast activation protein inhibitor (FAPI) in identifying mediastinal and hilar lymph node metastases and to develop a model to quantitatively and repeatedly identify lymph node status. METHODS: Twenty-seven patients with 137 lymph nodes were identified by two PET/CT images. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of lymph node status were analyzed, and the optimal cut-off value was identified by ROC analysis. RESULTS: The SUVmax of metastatic lymph nodes on 18F-FAPI was higher than that on 18F-FDG PET/CT (10.87 ± 7.29 vs 6.08 ± 5.37, p < 0.001). 18F-FAPI presented much greater lymph node detection sensitivity, specificity, accuracy, PPV and NPV than 18F-FDG PET/CT (84% vs. 71%; 92% vs. 67%; 90% vs. 69%, 84% vs. 52%, and 92% vs. 83%, respectively). Additionally, the diagnostic effectiveness of 18F-FAPI in small lymph nodes was greater than that of 18F-FDG PET/CT (specificity: 96% vs. 72%; accuracy: 93% vs. 73%; PPV: 77% vs. 33%, respectively). Notably, the optimal cut-off value for specificity and PPV of 18F-FAPI SUVmax was 5.3; the optimal cut-off value for sensitivity and NPV was 2.5. CONCLUSION: 18F-FAPI showed promising diagnostic efficacy in metastatic mediastinal and hilar lymph nodes from lung cancer patients, with a higher SUVmax, especially in small metastatic nodes, compared with 18F-FDG. In addition, this exploratory work recommended optimal SUVmax cutoff values to distinguish between nonmetastatic and metastatic lymph nodes, thereby advancing the development of image-guided radiation. Trial registration ClinicalTrials.gov identifier: ChiCTR2000036091.


Assuntos
Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia
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