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Cancers Jun 2024HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of...
HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.
PubMed: 38927930
DOI: 10.3390/cancers16122225 -
Genes Jun 2024Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and... (Observational Study)
Observational Study
BACKGROUND
Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC).
METHODS
This exploratory, observational study integrated radiomic perspectives using computed tomography (CT) and genomic perspectives through next-generation sequencing (NGS) applied to liquid biopsies. Associations between radiomic features and genetic mutations were established using the Area Under the Receiver Operating Characteristic curve (AUC-ROC). Machine learning techniques, including Support Vector Machine (SVM) classification, aim to predict genetic mutations based on radiomic features. The prognostic impact of selected gene variants was assessed using Kaplan-Meier curves and Log-rank tests.
RESULTS
Sixty-six patients underwent screening, with fifty-seven being comprehensively characterized radiomically and genomically. Predominantly males (68.4%), adenocarcinoma was the prevalent histological type (73.7%). Disease staging is distributed across I/II (38.6%), III (31.6%), and IV (29.8%). Significant correlations were identified with mutations of p.Thr145Pro (shape_Sphericity), p.Arg167Gln (glszm_ZoneEntropy, firstorder_TotalEnergy), p.Asp2213Asn (glszm_GrayLevelVariance, firstorder_RootMeanSquared), and p.Asp1529Glu (glcm_Imc1). Patients with the p.Thr145Pro variant demonstrated markedly shorter median survival compared to the wild-type group (9.7 months vs. not reached, = 0.0143; HR: 5.35; 95% CI: 1.39-20.48).
CONCLUSIONS
The exploration of the intersection between radiomics and cancer genetics in NSCLC is not only feasible but also holds the potential to improve genetic predictions and enhance prognostic accuracy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Female; Lung Neoplasms; Middle Aged; High-Throughput Nucleotide Sequencing; Aged; Tomography, X-Ray Computed; Genomics; Mutation; Proto-Oncogene Proteins; Protein-Tyrosine Kinases; Prognosis; Adult; Anaplastic Lymphoma Kinase; Radiomics
PubMed: 38927739
DOI: 10.3390/genes15060803 -
Genes May 2024The gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the... (Review)
Review
The gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in , NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.
Topics: Humans; Cataract; Proto-Oncogene Proteins c-maf; Mutation, Missense; Male; Child, Preschool; Protein Domains; Exome Sequencing
PubMed: 38927621
DOI: 10.3390/genes15060686 -
Biomolecules Jun 2024() causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain...
() causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during infection has not been studied. Here, we established a mouse model of infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood-brain barrier (BBB) integrity during infection. The results showed that induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (, , , and ) and BBB-permeability marker genes (, , , and ), increased the expression of angiogenetic genes ( and ), reduced -induced tight junction disruption, and reactivated -induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a -infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of infection.
Topics: Animals; Blood-Brain Barrier; Quercetin; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Disease Models, Animal; MAP Kinase Signaling System; Meningitis; Haemophilus Infections; Signal Transduction; Haemophilus parasuis; Cytokines; Swine
PubMed: 38927100
DOI: 10.3390/biom14060696 -
Biomolecules May 2024Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and...
Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 () mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 () mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing -null keratinocytes. HRAS-expressing -null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components.
Topics: Keratinocytes; PPAR-beta; Animals; Mice; Stearoyl-CoA Desaturase; PPAR delta; Fatty Acids; Angiopoietin-Like Protein 4; Humans; Oleic Acid; Proto-Oncogene Proteins p21(ras); Fatty Acids, Monounsaturated; Skin Neoplasms
PubMed: 38927010
DOI: 10.3390/biom14060606 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the DTA (, , ) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism.
OBJECTIVE
To analyze the DTA (, , ) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism.
METHODS
Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed.
RESULTS
75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were (38.7%, 24/62), (9.7%, 6/62) and (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old ( =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) ( =0.002). The gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) ( =0.00).
CONCLUSION
Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with mutation should be vigilant for thromboembolic events.
Topics: Humans; Mutation; Dioxygenases; Middle Aged; Myeloproliferative Disorders; Thromboembolism; Retrospective Studies; Proto-Oncogene Proteins; DNA-Binding Proteins; Repressor Proteins; DNA Methyltransferase 3A; DNA (Cytosine-5-)-Methyltransferases; Male; Female; High-Throughput Nucleotide Sequencing
PubMed: 38926973
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.025 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model.
OBJECTIVE
To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model.
METHODS
A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance.
RESULTS
Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (), mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor.
CONCLUSION
This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis; Retrospective Studies; Middle Aged; Female; Male; Mutation; ROC Curve; Core Binding Factors; Nomograms; Adult; RUNX1 Translocation Partner 1 Protein; Proto-Oncogene Proteins c-kit; Proportional Hazards Models; Oncogene Proteins, Fusion; Core Binding Factor Alpha 2 Subunit
PubMed: 38926955
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.007 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the clinical significance, functional role and potential downstream mechanism of USP5 in acute myeloid leukemia (AML).
OBJECTIVE
To investigate the clinical significance, functional role and potential downstream mechanism of USP5 in acute myeloid leukemia (AML).
METHODS
The expression of in AML and normal tissues and its correlation with patients' survival were analyzed based on TCGA database. was knocked down and overexpressed in Jurkat and HL-60 cells using lentivirus. USP5 mRNA and protein expression were detected by RT-qPCR and Western blot, respectively. Cell proliferation and growth were measured by CCK-8 and methylcellulose colony-forming assay. Flow cytometry was used to analyze cell cycle and apoptosis.
RESULTS
was highly expression in AML compared with normal tissues. Up-regulation of was negatively correlated with the survival of AML patients. knockdown and overexpression inhibited and promoted the proliferation and colony growth of AML cells, respectively. Cell cycle arrest and apoptosis were induced in knockdown Jurkat and HL-60 cells. Furthermore, knockdown inhibited the phosphrylation of AKT, mTOR and 4EBP1.
CONCLUSION
Overexpression of predicts poor survival of AML patients. Targeting USP5 suppresses AKT/mTOR/4EBP1 signaling and reduces the proliferation and growth of AML cells.
Topics: Humans; Leukemia, Myeloid, Acute; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Cell Proliferation; HL-60 Cells; Apoptosis; Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Jurkat Cells; Ubiquitin-Specific Proteases; Clinical Relevance
PubMed: 38926952
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.004 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the effects of the serine/threonine kinase family member 1 () gene on the proliferation and apoptosis of acute myeloid leukemia (AML) U937 cells, and the...
OBJECTIVE
To investigate the effects of the serine/threonine kinase family member 1 () gene on the proliferation and apoptosis of acute myeloid leukemia (AML) U937 cells, and the regulation effect on Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway.
METHODS
Bone marrow mononuclear cells from newly diagnosed adult AML patients and patients with iron deficiency anemia were collected and mRNA expression was detected by RT-qPCR. AML cell line U937 cells were divided into U937 group (U937 cells were cultured normally), Si-PIM1 group (U937 cells were transfected with low expression adenovirus vector containing mRNA), Si-NC group (U937 cells were transfected with low expression adenovirus vector without mRNA), coumermycin A1 (CoA1) group (JAK2 activator CoA1 was added to U937 cells at a concentration of 20 μmol/L), and Si-PIM1+CoA1 group (U937 cells were transfected with adenoviral vector containing low expression of mRNA and added with CoA1 at a concentration of 20 μmol/L). After culture for 24 h, the expressions of mRNA and protein, JAK2/STAT3 pathway, cell cycle and apoptosis-related proteins in U937 cells were detected by RT-qPCR and Western blot, the cell proliferation activity was detected by MTT assay, and flow cytometry was used to detect cell cycle changes and apoptosis rate.
RESULTS
The mRNA expression level in bone marrow mononuclear cells in AML patients was higher than that in patients with iron deficiency anemia ( < 0.05). Compared with U937 group, mRNA and protein, phosphorylated JAK2 (p-JAK2)/JAK2, phosphorylated STAT3 (p-STAT3)/STAT3, Cyclin D1, cyclin-dependent kinase 2 (CDK2) protein, cell proliferation activity, S phase and G /M phase proportions were decreased in Si-PIM1 group (all < 0.05), while p27, Caspase-3 protein, G/G phase proportion and apoptosis rate were increased (all < 0.05). However, the changes of above indicators in CoA1 group were just opposite to those in Si-PIM1 group, indicating that CoA1 could reverse the effect of Si-PIM1 on U937 cells. There were no significant differences in above indexes of U937 cells between U937 group, Si-PIM1+CoA1 group and Si-NC group ( >0.05).
CONCLUSION
Knockdown of gene expression can inhibit U937 cell proliferation and promote apoptosis, in order to alleviate ALM process, which may be related to the inhibition of JAK2/STAT3 pathway activation.
Topics: Humans; Janus Kinase 2; Proto-Oncogene Proteins c-pim-1; STAT3 Transcription Factor; Cell Proliferation; Apoptosis; Signal Transduction; Leukemia, Myeloid, Acute; U937 Cells
PubMed: 38926951
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.003 -
Journal of Cardiothoracic Surgery Jun 2024The purpose of this study is to investigate whether gene mutations can lead to the growth of malignant pulmonary nodules.
PURPOSE
The purpose of this study is to investigate whether gene mutations can lead to the growth of malignant pulmonary nodules.
METHODS
Retrospective analysis was conducted on patients with pulmonary nodules at Hebei Provincial People's Hospital, collecting basic clinical information such as gender, age, BMI, and hematological indicators. According to the inclusion and exclusion criteria, 85 patients with malignant pulmonary nodules were selected for screening, and gene mutation testing was performed on all patient tissues to explore the relationship between gene mutations and the growth of malignant pulmonary nodules.
RESULTS
There is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules (P < 0.05), while there is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules in the subgroup of invasive malignant pulmonary nodules (P < 0.05).
CONCLUSION
Mutations in the TP53 gene can lead to the growth of malignant pulmonary nodules and are correlated with the degree of invasion of malignant pulmonary nodules.
Topics: Humans; Male; Female; Retrospective Studies; Mutation; Middle Aged; Proto-Oncogene Proteins p21(ras); Lung Neoplasms; Tumor Suppressor Protein p53; Aged; Multiple Pulmonary Nodules; Adult; DNA Mutational Analysis; Genes, p53
PubMed: 38926874
DOI: 10.1186/s13019-024-02927-0