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1.
Genome Biol ; 25(1): 118, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741205

RESUMO

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.


Assuntos
Software , Humanos , Área Sob a Curva , Biologia Computacional/métodos
2.
bioRxiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38370825

RESUMO

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

3.
J Biophotonics ; 16(12): e202300193, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37556310

RESUMO

Colorectal cancer is a prevalent malignancy globally, often linked to chronic colitis. Terahertz technology, with its noninvasive and fingerprint spectroscopic properties, holds promise in disease diagnosis. This study aimed to explore terahertz technology's application in colitis-associated cancer using a mouse model. Mouse colorectal tissues were transformed into paraffin-embedded blocks for histopathological analysis using HE staining. Terahertz transmission spectroscopy was performed on the tissue blocks. By comparing terahertz absorption differences, specific frequency bands were identified as optimal for distinguishing cancerous and normal tissues. The study revealed that terahertz spectroscopy effectively differentiates colitis-related cancers from normal tissues. Remarkably, 1.8 THz emerged as a potential optimal frequency for diagnosing colorectal cancer in mice. This suggests the potential for rapid histopathological diagnosis of colorectal cancer using terahertz technology.


Assuntos
Neoplasias Colorretais , Espectroscopia Terahertz , Humanos , Espectroscopia Terahertz/métodos , Neoplasias Colorretais/diagnóstico
4.
Nano Lett ; 23(16): 7665-7674, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37535903

RESUMO

Precise manipulation of cancer cell death by harnessing reactive oxygen species (ROS) is a promising strategy to defeat malignant tumors. However, it is quite difficult to produce active ROS with spatial precision and regulate their biological outcomes. We succeed here in selectively generating short-lived and lipid-reactive hydroxyl radicals (•OH) adjacent to cancer cell membranes, successively eliciting lipid peroxidation and ferroptosis. DiFc-K-pY, a phosphorylated self-assembling precursor that consists of two branched Fc moieties and interacts specifically with epidermal growth factor receptor, can in situ produce membrane-bound nanofibers and enrich ferrocene moieties on cancer cell membranes in response to alkaline phosphatase. Within the acidic tumor microenvironment, DiFc-K-pY nanofibers efficiently convert tumoral H2O2 to active •OH around the target cell membranes via Fenton-like reactions, leading to lipid peroxidation and ferroptosis with good cellular selectivity. Our strategy successfully prevents tumor progression with acceptable biocompatibility through intratumoral administration.


Assuntos
Nanofibras , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Metalocenos , Peróxido de Hidrogênio/metabolismo , Morte Celular , Neoplasias/terapia , Oxirredução , Linhagem Celular Tumoral , Microambiente Tumoral
5.
NAR Cancer ; 5(1): zcad012, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36879684

RESUMO

Immune checkpoint inhibitors (ICIs) have led to durable responses in cancer patients, yet their efficacy varies significantly across cancer types and patients. To stratify patients based on their potential clinical benefits, there have been substantial research efforts in identifying biomarkers and computational models that can predict the efficacy of ICIs, and it has become difficult to keep track of all of them. It is also difficult to compare findings of different studies since they involve different cancer types, ICIs, and various other details. To make it easy to access the latest information about ICI efficacy, we have developed a knowledgebase and a corresponding web-based portal (https://iciefficacy.org/). Our knowledgebase systematically records information about latest publications related to ICI efficacy, predictors proposed, and datasets used to test them. All information recorded is checked carefully by a manual curation process. The web-based portal provides functions to browse, search, filter, and sort the information. Digests of method details are provided based on the original descriptions in the publications. Evaluation results of the effectiveness of the predictors reported in the publications are summarized for quick overviews. Overall, our resource provides centralized access to the burst of information produced by the vibrant research on ICI efficacy.

6.
Small Methods ; 7(5): e2201416, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36965100

RESUMO

Immunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug-loaded, cascade-targeted, and enzyme-instructed self-assembling peptide nanomedicine (Comp. 4) for ICD-based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD-L1) binding peptide sequence (NTYYEDQG) and a mitochondria-specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a -GD FD FpD Y- assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD-L1. Moreover, the presence of PD-L1- and mitochondria-specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD-based antitumor immunity.


Assuntos
Antígeno B7-H1 , Neoplasias , Animais , Camundongos , Morte Celular Imunogênica , Imunoterapia , Fosfatase Alcalina , Peptídeos , Corantes , Neoplasias/terapia
7.
Arch Oral Biol ; 147: 105632, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36736069

RESUMO

OBJECTIVE: The present study aimed to investigate whether Ginsenoside Rg1 alleviated lipopolysaccharide (LPS) - induced pyroptosis of human periodontal ligament cells (HPDLCs) and further explore the underlying mechanism. DESIGN: Cell viability was detected using the CCK-8 assay. Proinflammatory cytokine secretion and lactate dehydrogenase release were examined by ELISA. Flow cytometry analysis was conducted to determine the pyroptosis ratio, and ATP production was estimated using the ATP assay kit. Fluorescence staining was utilized to visualize mitochondrial morphology and analyze mitochondrial reactive oxygen species (mtROS), and the mitochondrial membrane potential level. Western blot and qRT-PCR were used to determine the expression of signaling pathway-related proteins and mRNA, respectively. RESULTS: The results discovered that Ginsenoside Rg1 treatment enhanced cell viability in comparison to LPS stimulation, attenuated pyroptosis in HPDLCs, and reduced the release of lactate dehydrogenase, IL-1ß, and IL-18 significantly. Additionally, we found that Ginsenoside Rg1 upregulated ATP content and mitochondrial membrane potential level while reducing aberrant mitochondrial fission and mtROS production. Mechanistically, we found that Ginsenoside Rg1 upregulated dynamin-related protein 1 (Drp1) phosphorylation at Ser 637 in an AMP-activated protein kinase (AMPK)-dependent manner, and reduced pyroptosis-related proteins expression, including NLRP3, ASC, Caspase-1, and GSDMD-NT. CONCLUSIONS: These findings demonstrate that Ginsenoside Rg1 treatment attenuates LPS-induced pyroptosis and inflammation damage in HPDLCs, which may connect to the activation of the AMPK/Drp1/NLRP3 signaling pathway. Moreover, the results offer a potential theoretical foundation for applying Ginsenoside Rg1 in inflammatory diseases such as periodontitis.


Assuntos
Lipopolissacarídeos , Piroptose , Humanos , Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por AMP , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ligamento Periodontal/metabolismo , Dinâmica Mitocondrial , Dinaminas , Trifosfato de Adenosina , Lactato Desidrogenases
8.
J Am Chem Soc ; 145(8): 4366-4371, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669158

RESUMO

Innovative methods for engineering cancer cell membranes promise to manipulate cell-cell interactions and boost cell-based cancer therapeutics. Here, we illustrate an in situ approach to selectively modify cancer cell membranes by employing an enzyme-instructed peptide self-assembly (EISA) strategy. Using three phosphopeptides (pY1, pY2, and pY3) targeting the membrane-bound epidermal growth factor receptor (EGFR) and differing in just one phosphorylated tyrosine, we reveal that site-specific phosphorylation patterns in pY1, pY2, and pY3 can distinctly command their preorganization levels, self-assembling kinetics, and spatial distributions of the resultant peptide assemblies in cellulo. Overall, pY1 is the most capable of producing preorganized assemblies and shows the fastest dephosphorylation reaction in the presence of alkaline phosphatase (ALP), as well as the highest binding affinity for EGFR after dephosphorylation. Consequently, pY1 exhibits the greatest capacity to construct stable peptide assemblies on cancer cell membranes with the assistance of both ALP and EGFR. We further use peptide-protein and peptide-peptide co-assembly strategies to apply two types of antigens, namely ovalbumin (OVA) protein and dinitrophenyl (DNP) hapten respectively, on cancer cell membranes. This study demonstrates a very useful technique for the in situ construction of membrane-bound peptide assemblies around cancer cells and implies a versatile strategy to artificially enrich cancer cell membrane components for potential cancer immunotherapy.


Assuntos
Neoplasias , Humanos , Neoplasias/metabolismo , Receptores ErbB/metabolismo , Membrana Celular/metabolismo , Fosforilação , Fosfopeptídeos/metabolismo , Fosfatase Alcalina/metabolismo
9.
Acta Biochim Biophys Sin (Shanghai) ; 55(2): 274-284, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36082934

RESUMO

Hypertrophic scar is a problem for numerous patients, especially after burns, and is characterized by increased fibroblast proliferation and collagen deposition. Increasing evidence demonstrates that lncRNAs contribute to the development and progression of various diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly characterized. In this study, a novel fibroblast proliferation-associated lncRNA, named lncRNA FPASL (MSTRG.389905.1), which is mainly localized in the cytoplasm, is found to be downregulated in hypertrophic scar, as detected by lncRNA microarray and qRT-PCR. The full-length FPASL is characterized and further investigation confirms that it has no protein-coding potential. FPASL knockdown in fibroblasts triggers fibroblast proliferation, whereas overexpression of FPASL directly attenuates the proliferation of fibroblasts. Furthermore, target genes of the differentially expressed lncRNAs in hypertrophic scars and the matched adjacent normal tissues are enriched in fibroblast proliferation signaling pathways, including the PI3K/AKT and MAPK signaling pathways, as determined by GO annotation and KEGG enrichment analysis. We also demonstrate that knockdown of FPASL activates the PI3K/AKT and MAPK signaling pathways, and specific inhibitors of the PI3K/AKT and MAPK signaling pathways can reverse the proliferation of fibroblasts promoted by FPASL knockdown. Our findings contribute to a better understanding of the role of lncRNAs in hypertrophic scar and suggest that FPASL may act as a potential novel therapeutic target for hypertrophic scar.


Assuntos
Cicatriz Hipertrófica , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cicatriz Hipertrófica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Proliferação de Células/genética , Fibroblastos/metabolismo
10.
Front Bioeng Biotechnol ; 10: 912562, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032710

RESUMO

Myocardial infarction (MI) is a serious threat to people's life and health, which is significantly hindered by effective treatment formulations. Interestingly, our recent endeavour of designing selenium-containing polymeric hydrogel has been experimentally proved to be helpful in combating inflammatory responses and treating MI. The design was inspired by selenium with anti-inflammatory and anti-fibrosis activities, and the formulation could also serve as a support of myocardial tissue upon the failure of this function. In details, an injectable selenium-containing polymeric hydrogel, namely, poly[di-(1-hydroxylyndecyl) selenide/polypropylene glycol/polyethylene glycol urethane] [poly(DH-SE/PEG/PPG urethane)], was synthesised by combining a thermosensitive PPG block, DH-Se (which has oxidation-reduction properties), and hydrophilic PEG segments. Based on the established mouse model of MI, this formulation was experimentally validated to effectively promote the recovery of cardiac function. At the same time, we confirmed by enzyme-linked immunosorbent assay, Masson staining and Western blotting that this formulation could inhibit inflammation and fibrosis, so as to significantly improve left ventricular remodelling. In summary, a selenium-containing polymeric hydrogel formulation analysed in the current study could be a promising therapeutic formulation, which can provide new strategies towards the effective treatment of myocardial infarction or even other inflammatory diseases.

11.
Biomater Sci ; 10(12): 3092-3098, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35522938

RESUMO

The development of novel vaccine adjuvants is essential for the production of modern vaccines against infectious agents and cancer. We recently reported a supramolecular hydrogel of a self-assembling D-tetra-peptide named Nap-GDFDFDY (Gel-gffy) that can evoke potent humoral and cellular immune responses; however, the determinants of its immunostimulatory properties were not characterized. In this study, we show that the amino acid sequence of the peptide determines the adjuvant potency of Gel-gffy. We designed and synthesized five Gel-gffy variants (Sol-gfgy, Sol-ggfy, Gel-gffg, Gel-gfyf, and Gel-gyff) by substituting the phenylalanine and tyrosine to glycine or changing the position of the tyrosine in the parent D-tetra-peptide. First, we characterized their gelation properties, nanomorphology, and secondary structure using transmission electron microscopy and circular dichroism; next, we examined their immunostimulatory properties. Gel-gfyf, Gel-gyff and Gel-gffy markedly upregulated maturation marker expression on bone marrow-derived dendritic cells. Moreover, the Gel-gfyf-, Gel-gyff- or Gel-gffy-encapsulated ovalbumin (OVA) vaccine induced robust humoral and cellular immune response in vivo. Notably, Gel-gffy had the strongest immunostimulatory activity. Our findings demonstrate that both the position and number of aromatic amino acids are crucial in determining the adjuvant potency of Gel-gffy, thus providing a valuable insight into designing peptide hydrogels as vaccine adjuvants.


Assuntos
Hidrogéis , Vacinas , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Sequência de Aminoácidos , Hidrogéis/química , Ovalbumina/química , Peptídeos , Tirosina
12.
Talanta ; 239: 123078, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34823863

RESUMO

Alkaline phosphatase (ALP) exists in both normal and pathological tissues. Spatiotemporal variations in ALP levels can reveal its potential physiological functions and changes that occur during pathological conditions. However, it is still challenging to exploit fluorescent probes that can measure ALP activity under good spatial and temporal resolutions. Herein, enzyme-instructed self-assembly (EISA) was used to construct a high-performing analytical tool (MN-pY) to probe ALP activity. MN-pY alone (free state) showed negligible fluorescence but presented an almost 13-fold increase in fluorescence intensity in the presence of ALP (assembly state). Mechanism study indicated the increase in fluorescence intensity was due to hydrogelation and formation of supramolecular fibrils, mainly consisting of dephosphorylated MN-Y. The dephosphorylation and further fibrillation of MN-pY could induce the formation of a "hydrophobic pocket", leading to a further increase in fluorescence intensity. Moreover, MN-pY could selectively illuminate HeLa cells with a higher ALP expression but not LO2 cells with lower ALP levels, promising a potential application in cancer diagnosis.


Assuntos
Fosfatase Alcalina , Corantes Fluorescentes , Fluorescência , Células HeLa , Humanos
13.
Bioengineered ; 12(1): 8994-9005, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34643163

RESUMO

Long noncoding RNAs (lncRNAs) have been implicated in the progression of malignant tumors, including in clear cell renal cell carcinoma (ccRCC). However, the function and the specific mechanism of lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in ccRCC remains unknown. Thus, this study explored the role of NNT-AS1 in ccRCC. We evaluated NNT-AS1 expression in ccRCC specimens. Next, CCK-8 and Transwell assays were used to evaluate cell proliferation and metastatic abilities. The interaction between miR-137 and NNT-AS1 or Y-box binding protein 1 (YBX-1) was confirmed using a dual luciferase reporter assay. The results showed that NNT-AS1 was significantly upregulated in ccRCC specimens compared with normal tissues. Inhibition of NNT-AS1 restrained ccRCC proliferation and metastasis. Mechanistically, NNT-AS1 acted as a competitive endogenous RNA to sponge miR-137, which depressed ccRCC cells proliferation and metastasis. Moreover, with the use of bioinformatics analysis, the famous oncogene YBX-1 was selected as the potential target of miR-137. Luciferase assay also confirmed the interaction between miR-137 and YBX-1. Further functional studies demonstrated that the inhibition effect of NNT-AS1 knockdown on ccRCC carcinogenesis could be partially reversed by overexpression of YBX-1, suggesting that NNT-AS1 promotes ccRCC progression through the miR-137/YBX-1 pathway. In summary, these findings indicate that NNT-AS1 promotes ccRCC progression via the miR-137/YBX-1 pathway, which may provide a promising therapeutic target for renal cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteína 1 de Ligação a Y-Box/genética , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Proteína 1 de Ligação a Y-Box/metabolismo
14.
Adv Drug Deliv Rev ; 174: 482-503, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34015417

RESUMO

Peptide-based supramolecular hydrogels have shown great promise as drug delivery systems (DDSs) because of their excellent biocompatibility, biodegradability, biological function, synthetic feasibility, and responsiveness to external stimuli. Self-assembling peptide molecules are able rationally designed into specific nanoarchitectures in response to the different environmental factors under different circumstances. Among all stimuli that have been investigated, utilizing inherent biological microenvironment, such as metal ions, enzymes and endogenous redox species, to trigger self-assembly endows such systems spatiotemporal controllability to transport therapeutics more accurately. Materials formed by weak non-covalent interactions result in the shear-thinning and immediate recovery behavior. Thus, they are injectable via a syringe or catheter, making them the ideal vehicles to deliver drugs. Based on the above merits, self-assembling peptide-based DDSs have been applied to treat various diseases via direct administration at the lesion site. Herein, in this review, we outline the triggers for inducing peptide-based hydrogels formation and serving as DDSs. We also described the advancements of peptide-based supramolecular hydrogels for local drug delivery, including intratumoral, subcutaneous, ischemia-related tissue (intramyocardial, intrarenal, and ischemic hind limb), and ocular administration. Finally, we give a brief perspective about the prospects and challenges in this field.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Peptídeos/química , Animais , Química Farmacêutica/métodos , Humanos , Estrutura Molecular , Peptídeos/administração & dosagem
15.
Poult Sci ; 99(12): 7192-7201, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33248636

RESUMO

This article presents investigation of the flavor profile on 5 different regional Chinese smoked chicken samples using gas chromatography-ion mobility spectrometry analysis methods. Five batches of samples were obtained over the course of 6 mo. A total of 34 flavor substances were identified in the 5 smoked chicken samples, including 10 aldehydes, 7 alcohols, 4 ketones, 2 hydrocarbons, 3 heterocyclic compounds, 4 esters, 2 ethers, and 2 phenolic compounds. The whole spectral fingerprint visually displayed flavor differences and relations in 5 types of smoked chicken with local characteristics. Moreover, the orthogonal projections to latent structures discriminant analysis model revealed that these samples could be separately classified into 5 groups. Multivariate statistical analysis showed that 20 chemicals with higher Variable Importance for the Projection values were the key contributors to the differences of flavor in these 5 kinds of smoked chicken. N-nonanal, heptanal, n-nonanal, heptanal, furfurol, and hexanal were the main common flavor compounds in the 5 types of Chinese smoked chicken, whereas linalool, alpha-terpineol, 1,8-cineole, and anethole were the main characteristic flavor compounds of Goubangzi chicken (No. 1); gamma-butyrolactone, 2-acetylfuran, 2-methoxyphenol, 2-acetylpyrrole, and limonene were determined as the key flavor compounds of Liaocheng chicken (No. 2); the concentration of octanal and n-nonanal was higher in Tangqiao chicken (No. 3); butyl acetate was the key contributor to the flavor compounds of Jinshan chicken (No. 4). 2-Heptanone and 2-pentylfuran had a high correlation with Zhuozishan chicken (No. 5). The different raw materials and ingredients used, especially the method of preparation and cultural differences, in different regions of the country in China were the main reasons leading to the similarities and differences of volatile compounds in the 5 kinds of Chinese traditional smoked chicken.


Assuntos
Galinhas , Análise de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Mobilidade Iônica , Produtos Avícolas , Compostos Orgânicos Voláteis , Animais , China , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Espectrometria de Mobilidade Iônica/veterinária , Produtos Avícolas/análise , Fumaça , Compostos Orgânicos Voláteis/análise
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(2): 623-628, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30998181

RESUMO

OBJECTIVE: To study the distribution of monoclonal gammopathy of undetermined significance(MGUS) in different age, sex and ethnic people over 40 years old. METHODS: Five hundred and ninety-six people(over 40 years old) examened in the Health Examination center of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to September 2017 were selected. Among 596 people, male 310, female 286, Han people 488, and Uygur ethnic people 108. According to age, 596 people were divided into 3 groups, (40-59 years old group, 60-79 years old group, over 80 years old group). First, all samples were screened by capillary serum protein electrophoresis. If the suspected monoclonal bands were found in the electrophoretogram, and then the specific protein types were determined by serum immunofixation electrophoresis. RESULTS: The total incidence of MGUS in 596 screened population was 4.027%. The incidence of MGUS in 40-59 years old group, 60-69 years old group and over 80 years old group were 1.762%, 2.929% and 10% respectively, and the differences among the groups were statistically significant(P<0.05). The incidence of MGUS in male (5.806%) was significantly higher than that in female (2.097%)(χ2=5.177,P<0.05). Binary Logistic regression analysis showed that over 80 years old and male were independent risk factors for MGUS(P=0.001, OR=4.188, 95%CI: 1.814-9.673, P=0.048, OR=2.605, 95%CI: 1.009-6.725). The types of immunoglobulin in patients with MGUS were mostly IgG, IgG(66.7%) was significantly more than IgA (29.2%)(χ2=21.375,P<0.05),and there was no significant difference in the incidence of MGUS between people with in Kappa and Lambda. CONCLUSION: The age increase and male may increase the incidence of MGUS, the IgG is the most common type of immunoglobcdin in pathogenesis of MGUS, so the early screening should be done.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulinas , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 20-24, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738442

RESUMO

OBJECTIVE: To study the expression of SOX4 gene in patients with acute myeloid leukemia (AML) and its correlation with clinical features and prognosis, and to explore the role of this gene in acute myeloid leukemia. METHODS: The real-time guantitative PCR was used to detect the expression level of SOX4 gene in bone marrow of 96 patients with newby diagmsed AML, and the features and prognosis was analyzed. RESULTS: The level of SOX4 expression in the 96 AML patients was significantly higher than that in healthy controls (P<0.01), and the expression of SOX4 gene was not significanly different between M1-M5 (P<0.05). The expression of SOX4 gene was no significanly different between different sex, nationality, and remission after chemotherapy (P>0.05). In AML patients the SOX4 gene expression level did not significantly correlated with the white blood cell count, hemoglobin level, platelet count primitive cell count, reticulocyte count and other laboratory indexes ( P>0.05), while which correlated with the overall survival (OS) (P<0.01) and erent-free survival (EFS) (P<0.05). CONCLUSION: The high expression of SOX4 gene affects the survival time of patients (OS, EFS), suggesting that may be one of the unfavorable prognostic factors for the AML patients.


Assuntos
Leucemia Mieloide Aguda , Fatores de Transcrição SOXC/genética , Medula Óssea , Humanos , Contagem de Leucócitos , Prognóstico , Fatores de Transcrição SOXC/metabolismo
18.
Oncotarget ; 8(41): 69916-69923, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050251

RESUMO

Recent studies suggest that SF3B1 might be related to poor prognosis in CLL, but the results remain controversial. This meta-analysis was performed to clarify the relationship between SF3B1 mutation and prognosis in patients with CLL. The relevant published reports were searched in PubMed, EMBASE, and Web of Science. A total of 13 articles were included in this meta-analysis as they met the inclusion and exclusion criteria. The hazard ratios (HRs) and corresponding 95% confidence intervals (95%CIs) for progression free survival (PFS) and/or overall survival (OS) were extracted from each eligible study. The pooled HR evaluating SF3B1 mutation on PFS was 1.81(95%CI 1.33-2.46, I2=78.9%, P<0.001) and on on OS was 2.57(95%CI 1.68-3.94, I2=79.3%, P<0.001) by random effects model. In conclusion, SF3B1 mutation was significantly associated with poor PFS and OS in CLL. It could be consider as a potential prognostic factor in patients with CLL.

19.
Int Immunopharmacol ; 40: 57-64, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27584054

RESUMO

OBJECTIVE: This study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL). METHODS: Totally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR. RESULTS: Treg and Th17 cell proportions in peripheral blood in the CLL patients were significantly higher than control. Serum levels of IL-10 and IL-17, and expression of Foxp3 and RORγt, were significantly increased in the CLL patients. Ratios of Treg/Th17 and IL-10/IL-17 were significantly elevated in the CLL patients. Compared with those before treatment, Treg/Th17 and IL-10/IL-17 ratios were declined in the CLL patients in remission. Compared with the non-remission group, Treg cells were significantly decreased, while Th17 cells were significantly increased, resulting in decreased Treg/Th17 ratio, in the remission group. Moreover, the serum IL-10 level was significantly decreased, while the serum IL-17 level was significantly increased, resulting in declined IL-10/IL-17 ratio, in the remission group. Correlation analysis showed that, Treg and Th17 cell counts were significantly associated with CD38 and ZAP-70 expression in the CLL patients. Moreover, the IL-10/IL-17 ratio was also significantly associated with CLL prognostic factors. CONCLUSION: Altered Treg/Th17 and IL-10/IL-17 ratios in CLL would be aggravated along with the disease progression, which might be used as indicators for the disease prognosis.


Assuntos
Interleucina-10/sangue , Interleucina-17/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Idoso , Antineoplásicos/uso terapêutico , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Imunossupressores/uso terapêutico , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Prognóstico , Rituximab/uso terapêutico , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 318-21, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948178

RESUMO

OBJECTIVE: To investigate the expression of nuclear antigen Ki-67 in CLL patients and realationship of Ki-67 expression with other clinical parameters. METHODS: Twenty-Six confirmed cases of CLL were analysised retrospectively. The immhnohistochemical method was carried out to examine the expression of Ki-67 in bone marrow cells, the flow cytometer was used to detect ZAP70 (Zeta chain-associated protein), CD38 and other markers, additionally, a panel of probes RB1 (13q14), ATM (11q22.3), P53 (17p13.1) and CSP12 (+12) FISH were perfomed to detect the cytogenetic abnormalities. RESULTS: Out of 26 patients, 15 cases (57.7%) showed positive expression of Ki-67, 11 cases (42.3%) showed negative expression of Ki-67, the average rate of Ki-67 positive expression was (10.86±7.36)%. The level of Ki-67 did not relate with sex, age, Hb, platelet, ZAP70, ATM. ß2-MG, IgHV and P53, but related to the Rai staging (P=0.01, r=0.517), CD38 (P=0.02, r=0.469), 13q14 (P=0.021, r=-0.48), and there was statistically significant difference (P<0.05). CONCLUSION: The Ki-67 level is higher in progressive stage of CLL and the Ki-67 expression is related with Rai staging, CD38, 13q14. The expression level of Ki-67 may be used as indicator for evaluation of CLL prognosis and guiding treatment for this disease.


Assuntos
Leucemia Linfocítica Crônica de Células B , Células da Medula Óssea , Aberrações Cromossômicas , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Antígeno Ki-67 , Prognóstico , Proteína-Tirosina Quinase ZAP-70
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