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Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.
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@#Objective To construct luciferase reporter plasmids of truncated fragments of different lengths of human guanylate binding protein 5(GBP5)gene promoter and analyze the transcriptional activity of each fragment to determine the core regulatory region.Methods GBP5promoter sequence was amplified by PCR,truncated into five fragments of different lengths and connected to pGL3-basic plasmid.The constructed recombinant plasmids pGL3-GBP5-11/21/31/41/51were transfected into 293FT cells and detected for luciferase activity.The binding sites of transcription factors in GBP5promoter region were predicted by JASPAR software,and Yin-Yang transcription factor 1(YY1)targeting the core regulatory region was selected and verified for the transcriptional regulatory activity.The CDS sequence of YY1 was amplified by PCR to construct the overexpression plasmid pIRES2-EGFP-YY1,which was then co-transfected to 293FT cells with plasmids pGL3-GBP5-21(-1 623 ～ +47 bp)and internal reference plasmid pRL-CMV,and detected for luciferase activity to analyze the regulation of transcription factor YY1 on GBP5 promoter activity.Results Colony PCR and double enzyme digestion identification proved that the plasmid of human GBP5 promoter reporter gene was correctly constructed;JASPAR software predicted that there were multiple transcription factor binding sites such as STAT1,YY1 and Foxp3 in GBP5promoter region.Double luciferase activity assay showed that pGL3-GBP5-21(-1 623 ～ +47 bp)showed the highest promoter activity,while the promoter activity of pGL3-GBP5-41(-520 ～ +47 bp)decreased significantly,suggesting that the core region of GBP5 promoter was located at upstream-1 623 ～-520 bp of 5 'UTR;Overexpression of YY1 significantly activated the GBP5 promoter activity and regulated the expression of GBP5.Conclusion The core regulatory region of human GBP5 promoter was located in upstream-1 623 ～-520 bp of the 5 'UTR,with a binding site of transcription factor YY1 existing in this region.Meanwhile,overexpression of YY1 significantly effected the activity of GBP5 promoter.
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Abstract Objectives: Although miR-653-5p has been validated to participate in the progression of multiple types of cancer, the functional role of exosomal miR-653-5p derived from Mesenchymal Stem Cells (MSCs) in Laryngeal Papilloma (LP) has still remained elusive. Hence, this study aimed to investigate the role of MSCs-derived exosomal miR-653-5p in LP. Methods: LP tissues (n = 15) and adjacent normal tissues (n = 10) were collected to examine the expression level of miR-653-5p. The expression level of miR-653-5p in LP cells and normal cells was also detected. Then, miR-653-5p was overexpressed or silenced to explore its effects on the proliferation, migration, invasion, and apoptosis of LP cells. Thereafter, the effects of exosomal miR-653-5p derived from MSCs on LP cell progression and the potential regulatory mechanism of miR-653-5p were assessed. Results: It was revealed that the expression level of miR-653-5p was downregulated in LP tissues and cells. In addition, miR-653-5p suppressed the proliferation, migration, invasion, and apoptosis of LP cells. Exosomes derived from MSCs played a suppressive role in LP development and mediated the transmission of miR-653-5p to LP cells. Further exploration identified Basic leucine Zipper and W2 domains 2 (BZW2) as the target of miR-653-5p. More importantly, the rescue experiments revealed that MSCs-secreted exosomal miR-653-5p efficiently inhibited the aggressive phenotypes of LP cells, which could be significantly reversed by BZW2 overexpression in LP cells. Conclusion: MSCs-derived exosomal miR-653-5p exerted inhibitory effects on LP progression through targeting BZW2, which provided a novel idea for the therapy of LP. Clinical Trial registration number: chictr-ior-17011021.
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This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.
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Abstract Background: Relapse and metastasis of patients with Colorectal Cancer (CRC) is the major obstacle to the long-term life of patients. Its mechanisms remain defined. Methods: A total of 48 CRC patients were enrolled and 68 samples were obtained from the peripheral blood of patients before or after treatments in this study. Twenty non-cancer patients were also detected as a negative control. Circulating Tumor Cells (CTCs), including Epithelial CTCs (eCTCs), Mesenchymal (MCTCs), and epithelial/ mesenchymal mixed phenotypes (mixed CTCs), were identified by CanPatrolTM CTC enrichment and RNA in situ hybridization. The relationship between CTCs number and Progression-Free Survival (PFS) or Overall Survival (OS) was evaluated. Results: Thirty-four of 48 patients (70.8%) were found to have positive CTCs. Total CTCs and MCTCs in the post-treatment had a significant correlation PFS and OS. When total CTCs or MCTCs in 5 mL blood of patients were more than 6 CTCs or 5 MCTCs, PFS of the patients was significantly shorter (p < 0.05) than that in patients with less than 6 CTCs or 5 MCTCs. The patients with > 5 CTCs count changes were found to exhibit poor PFS and OS rates (p < 0.05). Conclusion: Total CTCs and MCTCs number detection in patients with colorectal cancer was very useful biomarker for predicting the prognosis of patients. Higher CTCs or MCTCs had poorer PFS and OS rates.
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Lipotoxicity,caused by intracellular lipid accumulation,accelerates the degenerative process of cellular senescence,which has implications in cancer development and therapy.Previously,camitine palmi-toyltransferase 1C (CPT1C),a mitochondrial enzyme that catalyzes carnitinylation of fatty acids,was found to be a critical regulator of cancer cell senescence.However,whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown.An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231,HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C.Cellular lipotoxicity was further confirmed by lipotoxicity assays.Significant changes were found in the lipidome of CPT1 C-depleted cells,including major alterations in fatty acid,diacylglycerol,triacylglycerol,oxidative lipids,cardiolipin,phosphatidylglycerol,phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin.This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialde-hyde and reactive oxygen species,signatures of lipid peroxidation and oxidative stress.Reduction of ATP synthesis,loss of mitochondrial transmembrane potential and down-regulation of expression of mito-chondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity,which could further result in cellular senescence.Taken together,this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence,suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.
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OBJECTIVE: Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder. METHODS: We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder. RESULTS: The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26-1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11-1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders. CONCLUSIONS: Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture.