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1.
Heliyon ; 10(11): e32360, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961913

RESUMO

Background: The presence of peripheral inflammatory cells has been linked to the prognosis of cancer. This study aims to investigate the distinct roles of absolute neutrophil count (ANC) and absolute monocyte count (AMC) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML), as well as their prognostic significance in RCC. Methods: We conducted a comprehensive analysis of peripheral immune cell data, clinicopathological data, and tumor characteristics in patients diagnosed with RCC or RAML from January 2015 to December 2021. Receiver operating characteristic (ROC) curves, as well as univariate and multivariate analyses, were employed to assess the diagnostic utility of AMC and ANC in differentiating between RCC and RAML. Kaplan-Meier curve analysis was used to study the survival of RCC patients with different AMC and ANC. The prognostic value of AMC and ANC in RCC was investigated using COX univariate and multivariate analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for bioinformatic correlation analysis. Results: A total of 1120 eligible patients were included in the study. The mean preoperative AMC and ANC in patients with RCC were found to be significantly higher compared to those in patients with RAML (P = 0.001 and P < 0.001, respectively). High preoperative AMC and ANC significantly correlated with smoking history, tumor length, gross hematuria, and high T Stage, N stage, and pathological grade. In multivariate analyses, an ANC> 3.205 *10^9/L was identified to be independently associated with the presence of RCC (HR = 1.618, P = 0.008). High AMC and ANC were significantly associated with reduced OS and PFS (P < 0.05), and ANC may be an independent prognostic factor. Public database analysis showed that signature genes of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) were highly expressed in ccRCC. Conclusions: Elevated preoperative ANC and AMC can distinguish RCC from RAML and predict poor prognosis in patients with RCC. Furthermore, the signature genes of TAMs and TANs exhibit high expression levels in clear cell RCC.

2.
J Orthop Surg Res ; 19(1): 240, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622736

RESUMO

OBJECTIVE: To assess the radiographic outcomes, clinical outcomes and complications of percutaneous kyphoplasty (PKP) with and without posterior pedicle screw fixation (PPSF) in the treatment of severe osteoporotic vertebral compression fractures (sOVCF) with nonunion. METHODS: This study involved 51 patients with sOVCF with nonunion who underwent PKP or PPSF + KP. The operation time, intraoperative blood loss, volume of injected bone cement, operation costs and hospital stays were all recorded. In addition, the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) were assessed separately for each patient before and after surgery. RESULTS: Compared with the PPSF + KP group, the PKP group had shorter operation time, less intraoperative blood loss, shorter hospital stays and fewer operation costs. However, cobb's angle improvement (13.4 ± 4.3° vs. 21.4 ± 5.3°), VWR improvement ratio (30.4 ± 11.5% vs. 52.8 ± 12.7%), HA (34.9 ± 9.0% vs. 63.7 ± 7.6%) and HM (28.4 ± 11.2% vs. 49.6 ± 7.7%) improvement ratio were all higher in PPSF + KP group than that in PKP group. In addition, the ODI index and VAS score in both groups were significantly decreased at the postoperative and final follow-up. PKP group's postoperative VAS score was significantly lower than that in PPSF + KP group, but there was no statistically significant difference in VAS score at the last follow-up. CONCLUSION: PKP and PPSF + KP can both effectively relieve the pain associated with sOVCF with nonunion. PPSF + KP can achieve more satisfactory vertebral reduction effects compared to PKP. However, PKP was less invasive and it has more advantages in shortening operation time and hospital stay, as well as decreasing intraoperative blood loss and operation costs.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Parafusos Pediculares , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas por Compressão/tratamento farmacológico , Perda Sanguínea Cirúrgica , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/tratamento farmacológico , Resultado do Tratamento , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/tratamento farmacológico , Cimentos Ósseos/uso terapêutico , Estudos Retrospectivos
3.
Stem Cells ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655883

RESUMO

Fully grown oocytes have the natural ability to transform two terminally differentiated gametes into a totipotent zygote representing acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1, Zar1, Padi6 and Npm2, designated as MFiTLSCs. MFiTLSCs exhibited unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodelled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for development of oocyte biology-based reprogramming technology.

5.
Heliyon ; 10(3): e25458, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327434

RESUMO

Obesity has a significant impact on endocrine function, which leads to metabolic diseases including diabetes, insulin resistance, and other complications associated with obesity. Development of effective and safe anti-obesity drugs is imperative and necessary. Equisetin (EQST), a tetramate-containing marine fungal product, was reported to inhibit bacterial fatty acid synthesis and affect mitochondrial metabolism. It is tempting to speculate that EQST might have anti-obesity effects. This study was designed to explore anti-obesity effects and underlying mechanism of EQST on 3T3-L1 adipocytes differentiated from 3T3-L1 cells. Oil Red O staining showed that EQST reduced lipid accumulation in 3T3-L1 adipocytes. Quantitative real-time polymerase chain reaction and Western blot analysis revealed that EQST significantly inhibited expression of adipogenesis/lipogenesis-related genes C/ebp-α, Ppar-γ, Srebp1c, Fas, and reduced protein levels. There was also increased expression of key genes and protein levels involved in lipolysis (Perilipin, Atgl, Hsl), brown adipocyte differentiation (Prdm16, Ucp1), mitochondrial biogenesis (Pgc1α, Tfam) and ß-oxidation Acsl1, Cpt1. Moreover, mitochondrial content, their membrane potential ΔΨM, and respiratory chain genes Mt-Co1, Cox7a1, Cox8b, and Cox4 (and protein) exhibited marked increase in expression upon EQST treatment, along with increased protein levels. Importantly, EQST induced expression and activation of AMPK, which was compromised by the AMPK inhibitor dorsomorphin, leading to rescue of EQST-downregulated Fas expression and a reduction of the EQST-increased expression of Pgc1α, Ucp1, and Cox4. Together, EQST robustly promotes fat clearance through the AMPK pathway, these results supporting EQST as a strong candidate for the development into an anti-obesity therapeutic agent.

6.
Arab J Gastroenterol ; 25(1): 28-36, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38220479

RESUMO

BACKGROUND AND STUDY AIM: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide, and, more than half of these cases are diagnosed in China. However, effective treatment for HCC is still limited. MATERIAL AND METHODS: C-X-C motif chemokine receptor 4 (CXCR4) was first activated and inhibited in HepG2 cells using a pharmacological method. HepG2 cell proliferation was detected using the CCK-8 method. Metastasis and apoptosis of HepG2 cells were detected using wound healing and flow cytometry. The expression of each target molecule related to metastasis and invasion, such as MMPs, E-cadherin and the PI3K/AKT/Mcl-1/PARP signaling pathway was detected by western blotting. The secretion of molecular metastases was detected using competitive ELISA. RESULTS: This study constructed a CXCR4 activation and inhibition model in HepG2 cells. CXCR4 inhibition promoted the inhibitory effect of plantamajoside on the proliferation and metastasis of cells, which led to apoptosis. Furthermore, we found that the expression of apoptosis-related proteins was increased after treatment with plantamajoside combined with CXCR4 inhibition. In addition, the expression and secretion of pro-metastatic proteins, including MMPs and E-cadherin were decreased. We also noticed that this effect might be mediated by the PI3K/AKT/Mcl-1/PARP signaling pathway. CONCLUSION: CXCR4 inhibition may contribute to the treatment of HCC. Inhibition of CXCR4 expression contributes to the therapeutic effect of plantamajoside; the effect of plantamajoside might be mediated by the PI3K/AKT/Mcl-1/PARP signaling pathway; and CXCR4 might be a therapeutic target of HCC.


Assuntos
Carcinoma Hepatocelular , Catecóis , Glucosídeos , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Fosfatidilinositol 3-Quinases/uso terapêutico , Proteína de Sequência 1 de Leucemia de Células Mieloides/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Movimento Celular , Apoptose , Caderinas , Receptores de Quimiocinas/uso terapêutico
7.
Prep Biochem Biotechnol ; 54(3): 382-392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37565933

RESUMO

In this study, we utilized the remarkable capabilities of Bacillus subtilis ls-45 during the fermentation process to generate pine nut peptide. Through gene sequencing, we confirmed the proficiency of Bacillus subtilis ls-45 in producing protease, thereby serving as a valuable enzymatic source for protein hydrolysis. Our investigation focused on examining the variations in amino acid types and quantities between enzymatic pine nut protein peptide (EPP) and fermented pine nut protein polypeptide (FPP). Furthermore, we conducted a comprehensive assessment of the in vitro antioxidant activities of EPP and FPP, encompassing measurements of their Hydroxyl radical scavenging rate, Total reducing capacity, Superoxide anion scavenging rate, and ABTS+ radical scavenging rate. Notably, FPP exhibited superior antioxidant capacity compared to EPP. By employing semi-inhibitory mass concentration (IC50) analysis, we determined that FPP displayed enhanced efficacy in neutralizing hazardous free radicals when compared to EPP.


Assuntos
Proteínas de Nozes , Pinus , Antioxidantes/farmacologia , Bacillus subtilis , Nozes , Peptídeos/farmacologia
8.
Autophagy ; 20(3): 712-713, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38054642

RESUMO

Reticulophagy is a selective autophagy of the endoplasmic reticulum (ER) mediated by cargo receptors. It plays a crucial role in ER quality control, yet the mechanisms that initiate reticulophagy remain poorly understood. Our study identified the multifunctional protein UVRAG (UV radiation resistance associated gene) as a novel regulator of reticulophagy. UVRAG interacts with sheet and tubular reticulophagy receptors, regulates the oligomerization of receptors and facilitates their interaction with LC3/GABARAP, critical for ER fragmentation and autophagosome targeting. Remarkably, we found that UVRAG's function in reticulophagy initiation is independent of its traditional role in macroautophagy. Furthermore, UVRAG enhances the degradation of ER-associated mutant proteins linked to diseases like diabetes. Our findings offer insights into the mechanisms of reticulophagy initiation and highlight UVRAG's therapeutic potential in ER-related diseases.


Assuntos
Autofagossomos , Autofagia , Autofagossomos/metabolismo , Proteínas de Transporte/metabolismo
9.
Aging (Albany NY) ; 15(23): 13753-13775, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38048211

RESUMO

PURPOSE: Immune checkpoint therapy (ICT) provides a new idea for the treatment of advanced clear cell renal cell carcinoma (ccRCC), which can bring significant benefits to patients. However, the clinical application of ICT is limited because of the lack of predictive biomarkers to select potential responders. This study aims to propose a new biomarker to predict the response to Nivolumab in patients with ccRCC. MATERIALS AND METHODS: The genes that significantly improve the prognosis of ccRCC were retrieved from The Cancer Genome Atlas (TCGA) database. The genomic and clinical data were from patients that had been registered in prospective clinical trials (CheckMate 009, CheckMate 010 and CheckMate 025). TCGA, Gene Expression Omnibus (GEO), and The Human Protein Atlas database were used to analyze the gene and protein expression of WD repeat-containing protein 72 (WDR72) in ccRCC. Gene Ontology (GO) & The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to dig relevant mechanisms of WDR72. Single sample gene set enrichment analysis (ssGSEA) was conducted to evaluate the role of WDR72 in immune infiltration. Cell proliferation assay, FAO and ATP quantification were used to explore and verify the molecular mechanisms. The expression of WDR72, FOXP3, CD8, and CPT1A was examined by IHC in 20 advanced ccRCC tissue samples at the Urology Department of our hospital. The MethSurv was used to identify PBRM1 and WDR72 gene methylation and its effect on prognosis of ccRCC. RESULTS: WDR72 is the most significant gene for improving overall survival (OS) in ccRCC. In all three checkmates, OS and progression free survival (PFS) were found to be significantly higher in WDR72 high expression group than that in WDR72 low expression group (P=0.040 and P=0.012, respectively), and similar conclusions could be drawn from the PBRM1-mutation (MUT) compared with the PBRM1-wildtype (WT) (P=0.007 and P=0.006, respectively). What's more, high expression of WDR72 plus PBRM1-MUT as a combinatorial biomarker showed improved OS (HR=0.388, P=0.0026) and PFS (HR=0.39, P=0.0066) compared to low expression of WDR72 plus PBRM1-WT. Functional enrichment analysis showed that WDR72 was closely positively related to fatty acid degradation and fatty acid beta oxidation pathway in ccRCC. In vitro experiments showed that high expression of WDR72 can promote fatty acids oxidation and inhibit the proliferation of ccRCC cells. Immune analysis revealed that WDR72 high expression was associated with decreased infiltration of Treg cells and low ssGSEA score of check-point. IHC results showed that WDR72 was negatively correlated with FOXP3 expression (r=-0.506, P=0.023) and positively correlated with CPT1A expression (r=0.529, P=0.017). CONCLUSIONS: The present study indicated that high expression of WDR72 may indicate a good prognosis of patients treated with Nivolumab and WDR72 expression combined with PBRM1 mutation could be more persuasive to predict the response for ICT in ccRCC patients.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Biomarcadores Tumorais/genética , Prognóstico , Nivolumabe , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Estudos Prospectivos , Fatores de Transcrição Forkhead , Ácidos Graxos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Proteínas de Ligação a DNA , Fatores de Transcrição/genética , Proteínas
10.
Virol J ; 20(1): 266, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968649

RESUMO

BACKGROUND: Omicron's high transmissibility and variability present new difficulties for COVID-19 vaccination prevention and therapy. In this article, we analyzed the sensitivity of vaccine-induced antibodies as well as the effect of booster vaccinations against Omicron sublineages. METHODS: We looked for Randomized Controlled Trials and cohort studies that reported the COVID-19 vaccines against Omicron sublineages up to 28 July 2022 through PubMed, the Cochrane Library, EMBASE, and Web of Science. Quantitative synthesis was carried out using Stata 16.0 and RevMa5.3, then the serum NT50 and antibody sensitivity to neutralize Omicron sublineages were assessed before and after booster vaccination. This study was registered with PROSPERO number CRD42022350477. RESULTS: This meta-analysis included 2138 patients from 20 studies, and the booster vaccination against Omicron sublineages showed a significant difference compared to 2 dosage: BA.1/BA.1.1 (SMD = 0.80, 95% CI: 0.75-0.85, P = 0.00), BA.2/BA.2.12.1 (SMD = 0.77, 95% CI: 0.69-0.85, P = 0.00), BA.3 (SMD = 0.91, 95% CI: 0.83-1.0, P = 0.00), and BA.4/5 (SMD = 0.77, 95% CI: 0.60-0.94, P = 0.00). The sensitivity of vaccines-induced antibodies decreased by at least 5-folds after booster vaccination, particularly in the case of BA.4/5 which had the most notable decline in vaccine effectiveness. CONCLUSION: After the booster vaccination, the NT50 and the neutralization ability of vaccine-induced antibodies increased, but the susceptibility of antibodies decreased compared with the control virus, which may be a clue for future Omicron sublineages prevention.


Assuntos
Anticorpos Monoclonais , COVID-19 , Humanos , Anticorpos Monoclonais/uso terapêutico , SARS-CoV-2/genética , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Anticorpos Antivirais , Anticorpos Neutralizantes
11.
Technol Cancer Res Treat ; 22: 15330338231198348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37981789

RESUMO

In recent years, genitourinary system tumors are common in people of all ages, seriously affecting the quality of life of patients, the pathogenesis and treatment of these diseases are constantly being updated and improved. Exosomes, with a lipid bilayer that enable delivery of their contents into body fluids or other cells. Exosomes can regulate the tumor microenvironment, and play an important role in tumor development. In turn, cellular and non-cellular components of tumor microenvironment also affect the occurrence, progression, invasion and metastasis of tumor. Non-coding RNAs have been shown to be able to be ingested and released by exosomes, and are seen as a potential tool in cancer diagnosis and treatment. Here, we summarize the effect of non-coding RNAs of exosome contents on the tumor microenvironment of genitourinary system tumor, expound the significance of non-coding RNAs of exosome in the occurrence, development, diagnosis and treatment of cancers.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Qualidade de Vida , Sistema Urogenital , RNA não Traduzido/genética
12.
Front Immunol ; 14: 1216094, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022595

RESUMO

Renal ischemia-reperfusion injury (IRI) is a non-negligible clinical challenge for clinicians in surgeries such as renal transplantation. Functional loss of renal tubular epithelial cell (TEC) in IRI leads to the development of acute kidney injury, delayed graft function (DGF), and allograft rejection. The available evidence indicates that cellular oxidative stress, cell death, microvascular dysfunction, and immune response play an important role in the pathogenesis of IRI. A variety of immune cells, including macrophages and T cells, are actively involved in the progression of IRI in the immune response. The role of B cells in IRI has been relatively less studied, but there is a growing body of evidence for the involvement of B cells, which involve in the development of IRI through innate immune responses, adaptive immune responses, and negative immune regulation. Therefore, therapies targeting B cells may be a potential direction to mitigate IRI. In this review, we summarize the current state of research on the role of B cells in IRI, explore the potential effects of different B cell subsets in the pathogenesis of IRI, and discuss possible targets of B cells for therapeutic aim in renal IRI.


Assuntos
Injúria Renal Aguda , Transplante de Rim , Traumatismo por Reperfusão , Humanos , Rim/patologia , Transplante de Rim/efeitos adversos , Traumatismo por Reperfusão/patologia , Transplante Homólogo/efeitos adversos , Injúria Renal Aguda/complicações
13.
EMBO J ; 42(23): e113625, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902287

RESUMO

ER-phagy is a selective autophagy process that targets specific regions of the endoplasmic reticulum (ER) for removal via lysosomal degradation. During cellular stress induced by starvation, cargo receptors concentrate at distinct ER-phagy sites (ERPHS) to recruit core autophagy proteins and initiate ER-phagy. However, the molecular mechanism responsible for ERPHS formation remains unclear. In our study, we discovered that the autophagy regulator UV radiation Resistance-Associated Gene (UVRAG) plays a crucial role in orchestrating the assembly of ERPHS. Upon starvation, UVRAG localizes to ERPHS and interacts with specific ER-phagy cargo receptors, such as FAM134B, ATL3, and RTN3L. UVRAG regulates the oligomerization of cargo receptors and facilitates the recruitment of Atg8 family proteins. Consequently, UVRAG promotes efficient ERPHS assembly and turnover of both ER sheets and tubules. Importantly, UVRAG-mediated ER-phagy contributes to the clearance of pathogenic proinsulin aggregates. Remarkably, the involvement of UVRAG in ER-phagy initiation is independent of its canonical function as a subunit of class III phosphatidylinositol 3-kinase complex II.


Assuntos
Retículo Endoplasmático , Raios Ultravioleta , Retículo Endoplasmático/metabolismo , Autofagia/genética , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Proteínas de Transporte/metabolismo , Estresse do Retículo Endoplasmático/genética
14.
J Phys Chem B ; 127(40): 8681-8689, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37782892

RESUMO

The assembly of artificial nano- or microstructured materials with tunable functionalities and structures, mimicking nature's complexity, holds great potential for numerous novel applications. Despite remarkable progress in synthesizing colloidal molecules with diverse functionalities, most current methods, such as the capillarity-assisted particle assembly method, the ionic assembly method based on ionic interactions, or the field-directed assembly strategy based on dipole-dipole interactions, are confined to focusing on achieving symmetrical molecules. But there have been few examples of fabricating asymmetrical colloidal molecules that could exhibit unprecedented optical properties. Here, we introduce a microfluidic and magnetic template-assisted self-assembly protocol that relies mainly on the magnetic dipole-dipole interactions between magnetized magnetic-plasmonic nanoparticles and the mechanical constraints resulting from the specially designed traps. This novel strategy not only requires no specific chemistry but also enables magnetophoretic control of magnetic-plasmonic nanoparticles during the assembly process. Moreover, the assembled asymmetrical colloidal molecules also exhibit interesting hybridized plasmon modes and produce exotic optical properties due to the strong coupling of the individual nanoparticle. The ability to fabricate asymmetrical colloidal molecules based on the bottom-up method opens up a new direction for the fabrication of novel microscale structures for biosensing, patterning, and delivery applications.

15.
Exp Gerontol ; 183: 112308, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821052

RESUMO

In this study, 50 SD adult male mice were used to create an Alzheimer's disease model. The mice's learning and memory abilities were evaluated using an eight-arm radial maze experiment, and changes in body weight and food intake were noted. This helped to better validate the improvement of Alzheimer's disease caused by pine nut peptide-zinc chelate (Korean pine). For a more thorough investigation, mice's brains were dissected, Endogenous mercaptan antioxidants (enzymes), which are markers of brain tissue, were assessed, and mouse gut flora was analyzed. The findings demonstrated that pine nut peptide-zinc chelate (Korean pine) can improve learning and memory, stop brain aging and damage, and control gut flora in mice. It may exert its effects by ameliorating decreased AChE levels and increased ChAT levels in the central cholinergic system, endogenous thiol antioxidants (enzymes) in the cerebral cortex, and by controlling the bacterial flora in the gut.


Assuntos
Doença de Alzheimer , Masculino , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Nozes , Antioxidantes/farmacologia , Peptídeos , República da Coreia , Zinco/farmacologia , Modelos Animais de Doenças
16.
Drug Dev Res ; 84(8): 1709-1723, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37732677

RESUMO

The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2-d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC50 = 2.82 nM) and strong antiproliferation activity against SU-DHL-6 cells (IC50 = 0.035 µM). Besides, S5 inhibited the phosphorylation of Akt, which is downstream of PI3Kδ, in concentration-dependent manner. In view of the significant improvement in potency of PI3Kδ and selectivity over other PI3K isoforms, Compound S5 deserved further investigation as a promising PI3Kδ inhibitor.


Assuntos
Inibidores de Proteínas Quinases , Pirimidinas , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Proliferação de Células , Pirimidinas/farmacologia
17.
ACS Appl Bio Mater ; 6(10): 4042-4059, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37725557

RESUMO

Early-stage screening of cancer is critical in preventing its development and therefore can improve the prognosis of the disease. One accurate and effective method of cancer screening is using high sensitivity biosensors to detect optically, chemically, or magnetically labeled cancer biomarkers. Among a wide range of biosensors, giant magnetoresistance (GMR) based devices offer high sensitivity, low background noise, robustness, and low cost. With state-of-the-art micro- and nanofabrication techniques, tens to hundreds of independently working GMR biosensors can be integrated into fingernail-sized chips for the simultaneous detection of multiple cancer biomarkers (i.e., multiplexed assay). Meanwhile, the miniaturization of GMR chips makes them able to be integrated into point-of-care (POC) devices. In this review, we first introduce three types of GMR biosensors in terms of their structures and physics, followed by a discussion on fabrication techniques for those sensors. In order to achieve target cancer biomarker detection, the GMR biosensor surface needs to be subjected to biological decoration. Thus, commonly used methods for surface functionalization are also reviewed. The robustness of GMR-based biosensors in cancer detection has been demonstrated by multiple research groups worldwide and we review some representative examples. At the end of this review, the challenges and future development prospects of GMR biosensor platforms are commented on. With all their benefits and opportunities, it can be foreseen that GMR biosensor platforms will transition from a promising candidate to a robust product for cancer screening in the near future.

18.
BMC Musculoskelet Disord ; 24(1): 605, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491231

RESUMO

BACKGROUND & OBJECTIVE: Little research was available to explore which surgical fixation was better between fixation of both clavicle and scapula and clavicle alone in management of floating shoulder injury. METHODS: Total 69 patients with floating shoulder injury receiving surgery from February 2005 to July 2020 participated in the study. 49 patients underwent fixation of the clavicle alone (Group C) while 20 patients underwent fixation of both clavicle and scapula (Group C + S). They were further divided into subgroups according to age: Group C1, Group C + S1 (age ≤ 55 years old) and Group C2, Group C + S2 (age>55 years old). The radiological parameter (glenopolar angle (GPA)) and clinical outcomes (Herscovici score, Constant-Murley shoulder outcome score (CSS score), and Visual Analogue Scale score (VAS score)) were collected and compared between these groups. The correlation between age and radiological parameter and clinical outcomes was calculated by the Spearman correlation analysis. RESULTS: All people were followed up for at least 1 year. The degree of change in GPA before and after surgery in Group C + S is significantly better than that in Group C. The Herscovici and CSS score in Group C + S2 were significantly higher than those in Group C2 at 1 month, 3 months and 1 year after surgery. However, no significant difference in Herscovici and CSS score was found at final follow-up (1 year after surgery) between Group C + S1 and Group C1. The VAS score in Group C + S2 at final follow-up was significantly lower than that in Group C2. No significant difference in VAS score at final follow-up was found between Group C + S1 and Group C1. In addition, the VAS score was negatively correlated with Herscovici and CSS score. No correlation was found between VAS score and GPA. CONCLUSIONS: Both types of surgical fixation are effective in management of floating shoulder injury. For young people with floating shoulder injury, both types of surgical fixation are equally effective. However, for older people with floating shoulder injury, fixation of both clavicle and scapula is better in prognosis than fixation of clavicle alone.


Assuntos
Fraturas Ósseas , Lesões do Ombro , Humanos , Idoso , Adolescente , Pessoa de Meia-Idade , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Clavícula/lesões , Estudos Retrospectivos , Fraturas Ósseas/cirurgia , Resultado do Tratamento , Escápula/diagnóstico por imagem , Escápula/cirurgia , Lesões do Ombro/cirurgia , Fixação Interna de Fraturas
19.
Medicine (Baltimore) ; 102(25): e34114, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37352031

RESUMO

Clinically, for testicular tumor patients with negative tumor markers, how to distinguish the malignant from the benign is a difficult problem. This study aimed to assess the clinical significance of the absolute monocyte count (AMC) in differential diagnosis of testicular germ cell tumor with stage S0 (TGCTS0) and benign testicular tumor. In this retrospective single-center study, a total of 90 patients newly diagnosed with benign testicular tumor or TGCTS0 were reviewed. All patients received surgical intervention as the primary treatment method. AMC and other clinicopathological parameters were analyzed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic power of investigated parameters, and to determine the optimal cutoff values. Kaplan-Meier curve analysis was used to study the survival of patients with TGCTS0. qRT-PCR and immunohistochemistry (IHC) were performed to examine the expression of C-C motif chemokine ligand 2 (CCL2) mRNA and protein respectively. Differential gene expression and functional enrichment analysis were performed using Gene Expression Omnibus and the Cancer Genome Atlas databases. The mean preoperative AMC in patients with TGCTS0 was significantly higher than that in patients with benign testicular tumor (P = .020). AMC > 0.485*10^9/L was identified to be associated with the presence of TGCTS0 (hazard ratio [HR] = 3.074, P = .026), and patients with higher AMC level had worse progression free survival (PFS) (P = .047). Furthermore, AMC combined with lactate dehydrogenase (LDH) achieved a better diagnostic efficacy for TGCTS0 (area under curve [AUC] = 0.695). Tumor-associated macrophages (TAMs) signature gene CCL2 was highly expressed in TGCT compared with normal testicular tissue. Functional enrichment analysis showed that CCL2 is closely involved in the Extracellular Matrix Organization pathway and positively correlated with the expression of various matrix metalloproteinases (MMPs). Elevated AMC may serve as a predictor of higher risk of TGCTS0, and CCL2 mediated TAMs infiltration and MMPs secretion is essential for the tumorigenesis of TGCT.


Assuntos
Monócitos , Neoplasias Testiculares , Masculino , Humanos , Monócitos/metabolismo , Biomarcadores Tumorais/metabolismo , Estudos Retrospectivos , Ligantes , Neoplasias Testiculares/patologia , Quimiocinas/metabolismo , Prognóstico , Quimiocina CCL2/metabolismo
20.
Life (Basel) ; 13(4)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37109561

RESUMO

Enhancing the capacity of fruit trees to propagate via cuttings is an important endeavor for the high-quality development of the fruit industry. Optimizing the conditions for the cutting propagation of mulberry seedlings is an important factor that influences the industrial production of this plant; however, the currently used mulberry breeding technology system is not mature. In this experiment, an orthogonal design was used to intercept semi-woody shoots of Yueshenda 10 as cuttings and set different hormone concentrations (200, 500, 800, and 1000 mg/L), different hormone types (NAA, IBA, IAA, and ABT-1), and different soaking times (10, 30, 60, and 120 min) for cuttings. The effects of the three factors on the rooting of mulberry cuttings were investigated by soaking the cuttings in clean water for 10 min as a control. The results showed that the primary and secondary order of the three factors affecting the rooting rate of cuttings was hormone concentration > hormone type > soaking time, and the concentration of exogenous hormones had a significant impact on all rooting indicators (p < 0.05). In addition, the rooting rate (66.24%), average number of roots (7.54 roots/plant), and rooting effect index (4.23) of Yueshenda 10 cuttings reached the optimal level when soaked with 800 mg/L ABT-1 for 30 min. The longest root length (10.20 cm) and average root length (4.44 cm) of cuttings achieved the best results when soaked with 800 mg/L NAA for 60 min and 500 mg/L NAA for 30 min, respectively. On balance, it is considered that the preferred solution is to soak the cuttings of Yueshenda 10 with 800 mg/L ABT1 solution for 0.5 h.

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