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4.
Clin Transl Oncol ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587602

ABSTRACT

PURPOSE: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have showed its benefits in clinical studies, and here we conducted a further evaluation on the safety and efficacy of this treatment strategy. METHODS: A systematic literature review was conducted in PubMed, Embase and Cochrane Library to identify clinical studies on ICIs and chemotherapy for metastatic breast cancer. The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS), and adverse events (AEs) were analyzed. Random or fixed effects models were used to estimate pooled Hazard ratio (HR), odds ratio (OR) and the data of 95% confidence interval (CI) depend on the Heterogeneity. Cochrane risk assessment tool was used to assess risk of bias. We also drew forest plots and funnel plots, respectively. RESULTS: Seven studies with intend-to-treat (ITT) population for 3255 patients were analyzed. ICIs pooled therapy showed clinical benefits compared with chemotherapy alone, improving PFS (HR = 0.81, 95% CI: 0.74-0.90) of patients with metastatic triple negative breast cancer (mTNBC), especially in patients with PD-L1-positive tumors. However, it had no effect on OS (HR = 0.92, 95% CI 0.85-1.01). Besides, mTNBC patients received pooled therapy were less frequently to have AEs (OR = 1.30, 95% CI: 1.09-1.54). In patients with metastatic Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, pooled therapy showed no benefit for PFS (HR = 0.80, 95% CI: 0.50-1.28) and OS (HR = 0.87, 95% CI: 0.48-1.58). CONCLUSION: Pooled therapy had improved PFS in mTNBC patients, especially in patients with PD-L1-positive tumors, and it was less likely to cause grade ≥ 3 AEs.

5.
Genet Test Mol Biomarkers ; 28(4): 144-150, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38657122

ABSTRACT

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.


Subject(s)
Asian People , Early Growth Response Protein 3 , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Schizophrenia , Humans , Schizophrenia/genetics , Polymorphism, Single Nucleotide/genetics , Early Growth Response Protein 3/genetics , Female , Male , Genetic Predisposition to Disease/genetics , Case-Control Studies , Adult , China/epidemiology , Asian People/genetics , Middle Aged , Genotype , Risk Factors , Gene Frequency/genetics , Alleles , Receptor, ErbB-4/genetics , East Asian People
6.
DNA Cell Biol ; 43(5): 219-231, 2024 May.
Article in English | MEDLINE | ID: mdl-38634815

ABSTRACT

Breast cancer risk have been discussed to be associated with polymorphisms in genes as well as abnormal DNA damage repair function. This study aims to assess the relationship between genes single nucleotide polymorphisms (SNPs) related to DNA damage repair and female breast cancer risk in Chinese population. A case-control study containing 400 patients and 400 healthy controls was conducted. Genotype was identified using the sequence MassARRAY method and expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was analyzed by immunohistochemistry assay. The results revealed that ATR rs13091637 decreased breast cancer risk influenced by ER, PR (CT/TT vs. CC: adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.032; CT/TT vs. CC: adjusted OR = 1.63, 95%CI: 1.14-2.35, p = 0.008) expression. Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.


Subject(s)
Ataxia Telangiectasia Mutated Proteins , Breast Neoplasms , DNA Repair , Genetic Predisposition to Disease , Ku Autoantigen , Polymorphism, Single Nucleotide , Receptors, Progesterone , Humans , Female , Breast Neoplasms/genetics , DNA Repair/genetics , Middle Aged , Ataxia Telangiectasia Mutated Proteins/genetics , Case-Control Studies , Adult , Ku Autoantigen/genetics , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Receptor, ErbB-2/genetics , DNA Damage/genetics , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Fanconi Anemia Complementation Group N Protein/genetics , Risk Factors
7.
Clin Transl Oncol ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38485857

ABSTRACT

BACKGROUND: Studies have shown that many exosomal microRNAs (miRNAs) can be used as non-invasive biomarkers of lung cancer, but their diagnostic and prognostic values need to be further clarified. METHODS: We conducted a systematic literature search in Web of Science, PubMed, and ScienceDirect databases, obtained relevant articles and extracted data, and used statistical methods and statistical software to comprehensively evaluate the diagnostic and prognostic value of exosomal miRNAs in lung cancer. REGISTRATION NUMBER: PROSPERO CRD42023447398. RESULTS: In terms of diagnosis, two exosomal miRNAs (miR-486-5p and miR-451a) were reported with the highest frequency in lung cancer patients, both of which had good diagnostic value. Compared with the control group, the pooled sensitivities of miR-486-5p and miR-451a were 0.80 (95% CI: 0.73-0.86) and 0.76 (95% CI: 0.60-0.87), specificities: 0.93 (95% CI: 0.63-0.99) and 0.85 (95% CI: 0.72-0.92), and AUCs: 0.85 (95% CI: 0.81-0.88) and 0.88 (95% CI: 0.84-0.90), for the respective miRNAs. For prognosis, in lung cancer patients with abnormally expressed exosomal miRNAs, miR-1290 was associated with PFS outcome; miR-382, miR-1246, miR-23b-3p, miR-21-5p, and miR-10b-5p were associated with OS outcome; miR-21 and miR-4257 were associated with DFS outcome; miR-125a-3p and miR-625-5p were associated with PFS and OS outcomes; miR-216b and miR-451a were associated with OS and DFS outcomes. CONCLUSIONS: Exosomal miRNAs are valuable biomarkers in lung cancer patients. Exosomal miR-486-5p and miR-451a can be used as new diagnostic biomarkers for lung cancer. Dysregulated exosomal miRNAs could serve as indicators of survival outcomes in lung cancer patients.

9.
ACS Nano ; 18(12): 9031-9042, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38470458

ABSTRACT

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting of acid-degradable copper hydride (CuH) nanoparticles was developed via a microfluidic synthesis. After coating with tumor-targeting hyaluronic acid (HA), the nanoplatform denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. Cu+ can induce apoptosis by relying on Fenton-like reactions and lead to cuproptosis by causing mitochondrial protein aggregation. Besides, the existence of H2 can enhance both cell death types by causing mitochondrial dysfunction and intracellular redox homeostatic disorders. In vivo experimental results further exhibit the desirable potential of HCP for killing tumor cells and inhibiting lung metastases, which will broaden the horizons of designing copper-based materials triggering apoptosis and cuproptosis for better antitumor efficacy.


Subject(s)
Copper , Nanoparticles , Microfluidics , Apoptosis , Hyaluronic Acid , Hydrogen
10.
ACS Nano ; 18(11): 7923-7936, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38445625

ABSTRACT

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.


Subject(s)
Cancer Vaccines , Neoplasms , Humans , Microfluidics , Immunotherapy , Neoplasms/therapy , Antigens, Neoplasm
11.
Acta Pharm Sin B ; 14(2): 795-807, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38322334

ABSTRACT

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

12.
Cell Death Dis ; 15(2): 153, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378679

ABSTRACT

Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.


Subject(s)
Breast Neoplasms , MicroRNAs , Female , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Breast Neoplasms/pathology , Proteolysis , In Situ Hybridization, Fluorescence , Cell Line, Tumor , Cell Proliferation/genetics , RNA/genetics , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic/genetics , Y-Box-Binding Protein 1/genetics , Y-Box-Binding Protein 1/metabolism , E2F1 Transcription Factor/metabolism
13.
Adv Healthc Mater ; 13(14): e2303683, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38386961

ABSTRACT

Employing tumor whole cells for tumor immunotherapy is a promising tumor therapy proposed in the early stage, but its therapeutic efficacy is weakened by the methods of eliminating pathogenicity and the mass ratio of the effective antigen carried by itself. Here, by adding gold ion to live cancer cells in the microfluidic droplets, this work obtains dead tumor whole cells with NIR-controlled catalytic ability whose pathogenicity is removed while plenary tumor antigens, major structure, and homing ability are reserved. The engineered tumor cell (Cell-Au) with the addition of prodrug provides 1O2 in an O2-free Russell mechanism, which serves better in a hypoxic tumor microenvironment. This tumor whole-cell catalytic vaccine (TWCV) promotes the activation of dendritic cells and the transformation of macrophages into tumor suppressor phenotype. In 4T1 tumor-bearing mice, the Cell-Au-based vaccine supports the polarization of cytotoxicity T cells, resulting in tumor eradication and long-term animal survival. Compared with antigen vaccines or adoptive cell therapy which takes months to obtain, this TWCV can be prepared in just a few days with satisfactory immune activation and tumor therapeutic efficacy, which provides an alternative way for the preparation of personalized tumor vaccines across tumor types and gives immunotherapy a new path.


Subject(s)
Cancer Vaccines , Gold , Immunotherapy , Animals , Gold/chemistry , Immunotherapy/methods , Mice , Cell Line, Tumor , Cancer Vaccines/immunology , Cancer Vaccines/chemistry , Mice, Inbred BALB C , Catalysis , Female , Tumor Microenvironment/immunology , Metal Nanoparticles/chemistry , Dendritic Cells/immunology , Humans , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/pathology
14.
Curr Pharm Des ; 29(33): 2655-2667, 2023.
Article in English | MEDLINE | ID: mdl-38018195

ABSTRACT

BACKGROUND: The outbreak of Corona Virus Disease 2019 (COVID-19) has resulted in millions of infections and raised global attention. Bitter almonds and licorice are both Traditional Chinese Medicines (TCM), often used in combination to treat lung diseases. Several prescriptions in the guidelines for the diagnosis and treatment of coronavirus disease 2019 (trial version ninth) contained bitter almond-licorice, which was effective in the treatment of COVID-19. However, the active ingredients, drug targets and therapeutic mechanisms of bitter almonds-licorice for the treatment of COVID-19 remain to be elucidated. METHODS: The active ingredients and targets were derived from the Traditional Chinese Medicine Systems Pharmacology (TCMSP). Meanwhile, targets associated with COVID-19 were obtained from the GeneCards database, PharmGkb database and DrugBank database. Then, the potential targets of bitter almond-licorice against COVID-19 were screened out. Protein-protein interaction (PPI) networks and core targets were analyzed through the String database and Cytoscape software. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed based on potential targets using R statistical software. Finally, molecular docking was used to validate the binding of the active ingredients to the core targets. RESULTS: The results of the TCMSP database showed that the bitter almond-licorice had 89 active components against COVID-19, involving 102 targets. PPI network and core target analysis indicated that IL-6, TNF, MAPK1, and IL1B were the key targets against COVID-19. In addition, GO and KEGG enrichment analysis showed that the bitter almond-licorice were involved in various biological processes through inflammation-related pathways such as TNF signaling pathway and IL-17 signaling pathway. Finally, molecular docking approaches confirmed the affinity between the active components of the bitter almond-licorice and the therapeutic targets. CONCLUSION: The bitter almond-licorice could be used to treat COVID-19 by inhibiting inflammatory responses and regulating cellular stress. This work is based on data mining and molecular docking, and the findings need to be interpreted with caution.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Glycyrrhiza , Prunus dulcis , Humans , Molecular Docking Simulation , Network Pharmacology , COVID-19 Drug Treatment , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional
15.
Microbiol Spectr ; : e0055023, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37732751

ABSTRACT

To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) in outpatients and to explore the consistency between genotype and phenotype of H. pylori antibiotic resistance. A retrospective study on outpatients screened with urea breath test for H. pylori infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the H. pylori infection was confirmed by rapid urease test (RUT) and H. pylori culture. For antibiotic resistance phenotype analysis, the H. pylori strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated H. pylori was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent H. pylori infection screening, and 3,306 H. pylori strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in H. pylori with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most H. pylori with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with H. pylori resistance. In short, this study demonstrated that drug resistance of H. pylori was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. IMPORTANCE Helicobacter pylori is a key bacterium that causes stomach diseases. There was a high prevalence of H. pylori in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of H. pylori in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. This study provides information on H. pylori infection and also provides guidance for clinical doctors' drug treatment.

16.
Nano Lett ; 23(17): 8081-8090, 2023 09 13.
Article in English | MEDLINE | ID: mdl-37615340

ABSTRACT

Since central cells are more malignant and aggressive in solid tumors, improving penetration of therapeutic agents and activating immunity in tumor centers exhibit great potential in cancer therapies. Here, polydopamine-coated Escherichia coli Nissle 1917 (EcN) bearing CRISPR-Cas9 plasmid-loaded liposomes (Lipo-P) are applied for enhanced immunotherapy in deep tumors through activation of innate and adaptive immunity simultaneously. After accumulation in the tumor center through hypoxia targeting, Lipo-P could be detached under the reduction of reactive oxygen species (ROS)-responsive linkers, lowering the thermal resistance of cancer cells via Hsp90α depletion. Owing to that, heating induced by polydopamine upon near-infrared irradiation could achieve effective tumor ablation. Furthermore, mild photothermal therapy induces immunogenic cell death, as bacterial infections in tumor tissues trigger innate immunity. This bacteria-assisted approach provides a promising photothermal-sensitized immunotherapy in deep tumors.


Subject(s)
Neoplasms , Probiotics , Humans , CRISPR-Cas Systems/genetics , Immunotherapy , Neoplasms/therapy , Escherichia coli/genetics , Liposomes
17.
BMC Cancer ; 23(1): 509, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37277745

ABSTRACT

OBJECTIVE: E2F1 has been confirmed to be highly expressed in a variety of cancers. To better understand the prognostic value of E2F1 in cancer patients, this study was conducted to comprehensively evaluate the prognostic value of E2F1 in cancer according to published data. METHOD: PubMed, Web of Science and CNKI database were searched until May 31th, 2022 by using key words to retrieve the published essays on the role of E2F1 expression in the prognostic value of cancer. The essays were identified according to the inclusion and exclusion criteria. The pooled result of hazard ratio and 95% confidence interval was calculated with Stata17.0 software. RESULT: A total of 17 articles were included in this study involved in 4481 cancer patients. The pooled results showed that higher E2F1 expression was significantly correlated with unfavorable overall survival (HR = 1.10, I2 = 95.3%, *PHeterogeneity = 0.000) and disease-free survival (HR = 1.41, I2 = 95.2%, *PHeterogeneity = 0.000) of cancer patients. Such a significant association of was maintained subgroup of sample size of patients (> 150: for OS, HR = 1.77, and for DFS, HR = 0.91; or < 150: for OS, HR = 1.93, and for DFS, HR = 4.39), ethnicity (Asian: for OS, HR = 1.65, and for DFS, HR = 1.08; or not Asian: HR = 3.55, and for DFS, HR = 2.87), the data from database (clinical: for OS, HR = 1.24, and for DFS, HR = 1.40; or database: for OS, HR = 2.29, and for DFS, HR = 3.09), paper published year (after 2014: for OS, HR = 1.90;and for DFS,HR = 1.87; or before 2014: for OS, HR = 1.40, and for DFS, HR = 1.22); cancer type (female specific cancer: for OS, HR = 1.41, and for DFS, HR = 0.64; or non-gender specific cancers: for OS, HR = 2.00, and for DFS, HR = 2.95). In addition, according to the database data, we also found that higher E2F1 expression level would lead to worse prognosis of patients, and the results were consistent with the statistical analysis results in the paper. CONCLUSION: E2F1 could be served as a prognostic biomarker in cancer patients and higher levels of in cancer patients could predict shorter overall survival and disease-free survival.


Subject(s)
Neoplasms , Humans , Female , Prognosis , Neoplasms/genetics , Neoplasms/metabolism , Disease-Free Survival , Progression-Free Survival , Gene Expression , E2F1 Transcription Factor/genetics , E2F1 Transcription Factor/metabolism
18.
Lipids Health Dis ; 22(1): 87, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37386459

ABSTRACT

OBJECTIVE: The atherogenic index of plasma (AIP), consisting of triglycerides and high-density lipoprotein cholesterol, is applied to estimate the cardiovascular disease risk. The evidence regarding the association between AIP and prehypertension or hypertension remains inconclusive. This study was conducted to investigate the association of AIP and prehypertension or hypertension in normoglycemic subjects in Japan. METHODS: In the present cross-sectional study, 15,453 normoglycemic participants aged 18 years or older in Gifu, Japan, were evaluated. The selected participants were separated into four groups in the light of AIP quartiles, ranging from the lowest quartile (Q1) to the highest quartile (Q4). And the association between AIP and prehypertension or hypertension was explored with multivariate logistic regression by gradually adjusting model. RESULTS: Among the 15,453 participants, aged of 43.7 ± 8.9 years, and of whom 45.5% were females, the prevalence rates of prehypertension or hypertension were 27.68% (4,278) and 6.23% (962) respectively. In multivariate logistic regression analyses, participants in the highest AIP quartile had an increase risk in prehypertension and hypertension, compared with participants the lowest one, the odds ratios (OR) were 1.15 (95%CI: 1.00-1.13, P = 0.045) for prehypertension and 1.54 (95%CI:1.16-2.04, P = 0.003) for hypertension after adjusting confounders. In subgroup analyses, the high risk of hypertension was also observed for female participants in the highest AIP quartile (Q4) (OR = 2.19, 95%CI: 1.37-3.49, P = 0.001), especially between the ages of 40 and 60 years (OR = 2.20, 95%CI: 1.24-3.88, P = 0.007). CONCLUSIONS: Higher AIP is significantly and positively associated with the risk of prehypertension or hypertension in normoglycemic subjects in Gifu, Japan, which was more pronounced in the female population, especially between the years of 40 and 60.


Subject(s)
Hypertension , Prehypertension , Humans , Female , Adult , Middle Aged , Male , Prehypertension/epidemiology , Cross-Sectional Studies , Japan/epidemiology , Hypertension/epidemiology , Cholesterol, HDL
19.
Aging (Albany NY) ; 15(12): 5734-5750, 2023 06 21.
Article in English | MEDLINE | ID: mdl-37348024

ABSTRACT

Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles in the initiation and progression of cancer. Here, we report that small nucleolar RNA host gene 3 (SNHG3) is a key regulator of breast cancer progression. We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in breast cancer. The effects of SNHG3 on breast cancer were investigated via in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and Western blot). The mechanism of SNHG3 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. We found that SNHG3 expression was upregulated in breast cancer tissues and that its high expression level was associated with poor survival. We also found that high SNHG3 expression was partly induced by STAT3. Moreover, SNHG3 knockdown significantly repressed breast cancer cell growth both in vitro and in vivo. In the cytoplasm, SNHG3 facilitated the expression of Casein kinase II-A1 (CSNK2A1) by absorbing miR-485-5p and recruiting the HuR protein, participating in the malignant progression of breast cancer. Taken together, our study reveals a SNHG3-based regulatory network, which plays an oncogenic role in breast cancer and suggests that SNHG3 may serve as a potential target for the diagnosis and treatment of breast cancer.


Subject(s)
Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Breast Neoplasms/genetics , Casein Kinase II/genetics , Casein Kinase II/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , In Situ Hybridization, Fluorescence , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics
20.
Pathol Res Pract ; 247: 154544, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37235911

ABSTRACT

MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.


Subject(s)
MicroRNAs , Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Neoplasms/diagnosis , Neoplasms/genetics , Proportional Hazards Models
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