Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The 5­year survival rate of patients diagnosed with the early stages of the disease is markedly higher than that of patients in the advanced stages. Therefore, identifying novel biomarkers and drug targets for CRC is critical for clinical practice. Zinc finger protein 169 (ZNF169) is a crucial transcription factor, and its role in CRC remains to be explored. The present study aimed to investigate the clinical relevance, function and underlying mechanisms of ZNF169 in CRC growth and proliferation. The Cancer Genome Atlas (TCGA) database was utilized to analyze the clinical relevance of ZNF169 in patients with CRC. Immunohistochemical staining was performed on tissue samples from patients with CRC to detect the expression of ZNF169. The HCT­116, HT­29 and RKO cell lines were employed for in vitro experiments. The overexpression and knockdown of ZNF169 were achieved by transfecting the cells with lentivirus and small interfering RNAs, respectively. Cell Counting Kit­8, colony formation and EdU staining assays were applied to investigate the function of ZNF169 in CRC cells. Dual luciferase activity and chromatin immunoprecipitation (ChIP)­quantitative PCR (qPCR) assays were performed to identify the regulatory effects of ZNF169 on the ankyrin repeat and zinc­finger domain­containing 1 (ANKZF1; also known as ZNF744) gene. Reverse transcription­quantitative PCR and western blot analysis were performed to measure mRNA and protein expression, respectively. The analysis of TCGA data revealed a positive correlation between ZNF169 and ANKZF1, with the overexpression of ANKZF1 being associated with a poor prognosis of patients with CRC. The experimental results demonstrated that ZNF169 was expression upregulated in CRC tissue compared with that in normal colon tissue. Gain­of­function and loss­of­function experiments revealed that ZNF169 enhanced the intensity of EdU staining, promoting the growth and proliferation of CRC cells. Furthermore, the overexpression of ZNF169 potentiated the transcriptional activity of the ANKZF1 gene, while the knockdown of ZNF169 produced the opposite results. ChIP­qPCR confirmed the interaction between ZNF169 and the promoter sequence of ANKZF1. Rescue experiments revealed that ZNF169 accelerated CRC cell growth and proliferation through the upregulation of ANKZF1. Furthermore, there was a positive correlation identified between ZNF169 and ANKZF1, and upregulation of ANKZF1 expression was associated with the poor prognosis of patients with CRC. On the whole, the present study demonstrates that ZNF169 contributes to CRC malignancy by potentiating the expression of ANKZF1. Thus, the regulation of ZNF169 and/or ANKZF1 expression may represent a viable strategy for the treatment patients with CRC with a high expression of ZNF169.

Hub biomarkers in ultrasound-guided bladder cancer and osteosarcoma: Myosin light chain kinase and caldesmon.

Bladder cancer and osteosarcoma are 2 types of cancers that originate from epithelial tissues inside the bladder and bone or muscle tissues. Ultrasound-guided biopsies provide crucial support for the diagnosis and treatment of bladder cancer and osteosarcoma. However, the relationship between myosin light chain kinase (MYLK) and caldesmon (CALD1) and bladder cancer and osteosarcoma remains unclear. The bladder cancer datasets GSE65635 and GSE100926, the osteosarcoma dataset GSE39058, were obtained from gene expression omnibus. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis. Gene expression heat map was drawn and immune infiltration analysis was performed. The comparative toxicogenomics database analysis were performed to find disease most related to core gene. Western blotting experiments were performed. TargetScan screened miRNAs that regulated central DEGs. We obtained 54 DEGs. Functional enrichment analysis revealed significant enrichment in terms of cellular differentiation, cartilage development, skeletal development, muscle actin cytoskeleton, actin filament, Rho GTPase binding, DNA binding, fibroblast binding, MAPK signaling pathway, apoptosis, and cancer pathways. Gene set enrichment analysis indicated that DEGs were primarily enriched in terms of skeletal development, cartilage development, muscle actin cytoskeleton, MAPK signaling pathway, and apoptosis. The immune infiltration analysis showed that when T cells regulatory were highly expressed, Eosinophils exhibited a similar high expression, suggesting a strong positive correlation between T cells regulatory and Eosinophils, which might influence the disease progression in osteosarcoma. We identified 6 core genes (SRF, CTSK, MYLK, VCAN, MEF2C, CALD1). MYLK and CALD1 were significantly correlated with survival rate and exhibited lower expression in bladder cancer and osteosarcoma samples compared to normal samples. Comparative toxicogenomics database analysis results indicated associations of core genes with osteosarcoma, bladder tumors, bladder diseases, tumors, inflammation, and necrosis. The results of Western blotting showed that the expression levels of MYLK and CALD1 in bladder cancer and osteosarcoma were lower than those in normal tissues. MYLK and CALD1 likely play a role in regulating muscle contraction and smooth muscle function in bladder cancer and osteosarcoma. The lower expression of MYLK and CALD1 is associated with poorer prognosis.

The occurrence and development of vertebral osteoporosis regulated by IL-8.

Vertebral osteoporotic fracture is a common type of fracture, and the incidence is higher in the elderly. However, the relationship between vertebral osteoporotic fractures and interleukin-8 (IL-8) remains unclear. A total of 163 patients with osteoporotic vertebral fractures were recruited. Clinical and follow-up data were recorded, and the expression levels of IL1, MMP9, IL-8, and C-reactive protein in blood were measured. Pearson Chi-square test and Spearman correlation coefficient were used to analyze the relationship between vertebral osteoporotic fractures and related parameters. Univariate and multivariate logistic regression and univariate and multivariate Cox proportional hazards regression were used for further analysis. Pearson chi-square test, Spearman correlation coefficient and Logistic regression analysis showed that IL1 and IL-8 were significantly associated with vertebral osteoporotic fractures. Univariate Cox regression analysis showed that age and IL-8 expression level were significantly associated with maintenance time from recovery to recurrence of vertebral osteoporotic fractures. Multivariate Cox regression analysis showed that IL-8 expression level was significantly associated with maintenance time from recovery to recurrence of vertebral osteoporotic fractures. The higher the expression level of IL-8, the more likely it is to develop vertebral osteoporotic fracture, and the more likely it is to relapse in a short time.

Effect of platelet content on occurrence and prognosis of distal radius fracture.

Fractures of the distal radius are a common fracture with an increasing incidence. However, the underlying factors for distal radius fractures (DRFs) remain unclear. A total of 123 patients with distal radial fractures were recruited. To document clinical and follow-up data, and measure the levels of white blood cells, hemoglobin, platelets, and red blood cells in the bloodstream for qualitative observation of their expression effects within the human body, specifically assessing whether the magnitudes of these indicators are associated with potential factors influencing DRF. Pearson chi-square test and Spearman correlation were used to analyze the relationship between DRF and related parameters. Univariate and multivariate logistic regression and multivariate Cox proportional risk regression were used for further analysis. Pearson chi-square test and Spearman correlation analysis showed a significant correlation between platelet and red blood cell levels and the occurrence of DRFs. Univariate logistic regression analysis demonstrated a significant correlation between platelet count (OR [odds ratio] = 6.286, 95% CI [confidence interval]: 2.862-13.808, P < .001) and red blood cell count (OR = 2.780, 95% CI: 1.322-5.843, P = .007) with DRFs. Increasing levels of both indicators were associated with a higher susceptibility to DRFs. Multivariate logistic regression showed that platelets (OR = 6.344, 95% CI: 2.709-14.855, P < .001) were significantly associated with DRFs. Multivariate Cox regression analysis showed sex (HR [hazard ratio] = 0.596, 95% CI: 0.381-0.931, P = .023) and platelet (HR = 3.721, 95% CI: 2.364-5.855, P < .001) were significantly associated with maintenance time from recovery to recurrence (MTRR) of DRFs. In other words, the platelet content in the body of different genders is different, and the MTRR of DRF is different. Platelets were significantly associated with DRFs. The higher the platelet count, the higher the risk of DRF and the shorter the time of DRF recurrence.

Metabolomics analyses of cancer tissue from patients with colorectal cancer.

The alteration of metabolism is essential for the initiation and progression of numerous types of cancer, including colorectal cancer (CRC). Metabolomics has been used to study CRC. At present, the reprogramming of the metabolism in CRC remains to be fully elucidated. In the present study, comprehensive untargeted metabolomics analysis was performed on the paired CRC tissues and adjacent normal tissues from patients with CRC (n=35) using ultra­high­performance liquid chromatography­mass spectrometry. Subsequently, bioinformatic analysis was performed on the differentially expressed metabolites. The changes in these differential metabolites were compared among groups of patients based on sex, anatomical tumor location, grade of tumor differentiation and stage of disease. A total of 927 metabolites were detected in the tissue samples, and 24 metabolites in the CRC tissue were significantly different compared with the adjacent normal tissue. The present study revealed that the levels of three amino acid metabolites were increased in the CRC tissue, specifically, N­α­acetyl­Îµ­(2­propenal)­Lys, cyclo(Glu­Glu) and cyclo(Phe­Glu). The metabolites with decreased levels in the CRC tissue included quinaldic acid (also referred to as quinoline­2­carboxilic acid), 17α­ and 17ß­estradiol, which are associated with tumor suppression activities, as well as other metabolites such as, anhydro­ß­glucose, Asp­Arg, lysophosphatidylcholine, lysophosphatidylethanolamine (lysoPE), lysophosphatidylinositol, carnitine, 5'­deoxy­5'­(methylthio) adenosine, 2'­deoxyinosine­5'­monophosphate and thiamine monophosphate. There was no difference in the levels of the differential metabolites between male and female patients. The differentiation of CRC also showed no impact on the levels of the differential metabolites. The levels of lysoPE were increased in the right side of the colon compared with the left side of the colon and rectum. Analysis of the different tumor stages indicated that 2­aminobenzenesulfonic acid, P­sulfanilic acid and quinoline­4­carboxylic acid were decreased in stage I CRC tissue compared with stage II, III and IV CRC tissue. The levels of N­α­acetyl­Îµ­(2­propenal)­Lys, methylcysteine and 5'­deoxy­5'­(methylthio) adenosine varied at different stages of tumorigenesis. These differential metabolites were implicated in multiple metabolism pathways, including carbohydrate, amino acid, lipid, nucleotide and hormone. In conclusion, the present study demonstrated that CRC tumors had altered metabolites compared with normal tissue. The data from the metabolic profile of CRC tissues in the present study provided supportive evidence to understand tumorigenesis.

CD3D and CD247 are the molecular targets of septic shock.

Septic shock is a serious systemic disease with circulatory failure and abnormal cell metabolism caused by sepsis. However, the relationship between CD3D and CD247 and septic shock remains unclear. The septic shock datasets GSE33118 and GSE142255 profiles were generated from the gene expression omnibus databases GPl570, GPl17586. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. The construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis (GSEA) were performed. Gene expression heat map was drawn. Immune infiltration analysis was performed. Comparative toxicogenomics database (CTD) analysis were performed to find the disease most related to the core gene. Targets can was used to screen miRNAs regulating the hub DEGs. 467 DEGs were identified. According to the gene ontology analysis, they were mainly enriched in the regulation of immune response, cell activation, signaling receptor activity, enzyme binding. Kyoto encyclopedia of genes and genomes analysis showed that they were mainly enriched in the TCR signaling pathway, Fc epsilon RI signaling pathway. GSEA showed that the DEGs were mainly enriched in immune response regulation, cell activation, TCR signaling pathway, Fc epsilon RI signaling pathway. Positive regulation of Fc receptor signaling pathway, PID IL12 2 pathway, immune response was observed in go enrichment items in the enrichment items of metascape. PPI networks got 5 core genes. Gene expression heat map showed that 5 core genes (CD247, Lck, cd3e, cd3d, ITK) were lowly expressed in the sepsis shock samples and highly expressed in the normal samples. CTD analysis showed that 5 core genes (CD247, Lck, cd3e, cd3d, ITK) were found to be associated with hemorrhage and necrosis. Low expression of cd3d, CD247 was observed in septic shock, and the lower the level of cd3d, CD247, the worse the prognosis.

Relationship between size and location of infarction beside lateral ventricle and motor recovery following rehabilitation.

BACKGROUND: The lesions besides lateral ventricle and motor recovery following rehabilitation have hardly been studied. OBJECTIVE: To explore the relationship between the size, location of infarction beside the lateral ventricle and motor recovery following rehabilitation. METHODS: A prospective cohort of 55 patients submitted to a Rehabilitation Medical Center between January 2015 and June 2019 who suffered a single cerebral infarction beside the lateral ventricle were included in the study. The size and distance between the posterior margin and the frontal-middle line (FML) of the lesion were measured. Follow-up was conducted until the recovery was no longer progressing. Barthel index and Brunstrom stages were used to evaluate the outcome (full recovery, partial recovery and poor recovery). Variance analysis and nonparametric test were used for the comparison between groups. Multivariate logistic regression analysis was used to screen the factors affecting the outcomes. The Pearson correlation coefficient was used to compare the volume of infarction, behind the FML and the outcomes. RESULTS: Among the 55 patients, the outcome was full recovery (n = 28), partial recovery (n = 13) and poor recovery (n = 14). Multivariate logistic regression analysis showed that volume and location of the infarction were significantly correlated with the outcome (p = 0.039, 0.050). The lesion volume in the full recovery patients was significantly smaller than that in the poor recovery patients (p < 0.01). The posterior edge of the lesion in the full recovery patients behind the FML was statistically significant compared with that in the poor recovery patients (p < 0.01). Spearman correlation analysis showed that the motor recovery was negative correlation to lesion volume (r = -0.508, P < 0.01) and location (r = -0.450, P < 0.01) of the infarction. CONCLUSION: The motor recovery of patients with cerebral infarction beside lateral ventricle is related to the volume and location of the lesion. The larger the volume of the lesion, and the farther the posterior margin of the lesion to the FML, the worse the motor recovery.