Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway.

We evaluated the expression profiles of differentially expressed miRNAs (DEmiRNAs) involved in human fetal skin development via high-throughput sequencing to explore the expression difference and the regulatory role of miRNA in different stages of fetal skin development. Analysis of expression profiles of miRNAs involved collecting embryo samples via high-throughput sequencing, then bioinformatics analyses were performed to validate DEmiRNAs. A total of 363 miRNAs were differentially expressed during the early and mid-pregnancy of development, and upregulated DEmiRNAs were mainly concentrated in the let-7 family. The transfection of let-7b-5p slowed down HaCaT cell proliferation and promoted apoptosis, as evidenced by the cell counting kit-8 assay, quantitative real-time polymerase chain reaction, and flow cytometry. The double luciferin reporter assay also confirmed let-7b-5p and ΔNp63 downregulation through the combination with the 3'-untranslated region of ΔNp63. Moreover, treatment with a let-7b-5p inhibitor upregulated ΔNp63 and activated the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. The let-7b-5p caused a converse effect on HaCaT cells because of Np63 upregulation. Let-7b-5p regulates skin development by targeting ΔNp63 via PI3K-AKT signaling, contributing to future studies on skin development and clinical scar-free healing.

The construction and validation of a frailty risk prediction model for older adults with lung cancer: A cross-sectional study.

OBJECTIVE: We aimed to construct and internally validate a frailty risk prediction model in older adults with lung cancer. METHOD: In total, 538 patients were recruited in a grade A tertiary cancer hospital in Tianjin, and patients were randomly divided into the training group (n = 377) and the testing group (n = 166) at a ratio of 7:3. The Frailty Phenotype scale was used to identify frailty and logistic regression analysis was used to identify the risk factors and establish a frailty risk prediction model. RESULTS: In the training group, logistic regression showed that age, fatigue-related symptom cluster, depression, nutritional status, D-dimer level, albumin level, presence of comorbidities, and disease course were independent risk factors for frailty. The areas under the curve (AUCs) of the training and testing groups were 0.921 and 0.872, respectively. A calibration curve of P = 0.447 validated model calibration. The decision curve analysis demonstrated greater clinical benefit when the threshold probability was >20%. CONCLUSION: The prediction model had a favorable prediction power for determining the risk of frailty, contributing to the prevention and screening of frailty. Patients with a frailty risk score of more than 0.374 should be regularly monitored for frailty and receive personalized preventive interventions.

Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1.

INTRODUCTION: Fluoride can induce the proliferation and activation of osteoblasts, resulting in skeletal fluorosis progression; however, the specific mechanism is unclear. METHODS: Cell proliferation was examined using the MTT assay. Flow cytometry was performed to detect the cell cycle distribution. Alkaline phosphatase (ALP) was calculated to evaluate bone formation and turnover. Gene methylation was examined using the MSP assay. mRNA and protein expression levels were assessed using qRT-PCR and Western blot assays. RESULTS: Low-concentration NaF treatment promoted the cell cycle progression of osteoblasts to S-phase, thus accelerating cell proliferation and activation in a concentration-dependent manner. In addition, the methylation of the MGMT and MLH1 genes was increased, and their mRNA expression was reduced. Furthermore, the DNA methyltransferase inhibitor 5-AZA-dC suppressed cell viability, cell number in S-phase, ALP activity and osteogenesis-related protein levels in osteoblasts treated with low doses of NaF. Meanwhile, 5-AZA-dC suppressed the increase in MGMT and MLH1 gene methylation in osteoblasts treated with low doses of NaF, leading to enhanced expression of MGMT and MLH1 mRNA. CONCLUSION: NaF treatment led to methylation of the DNA repair genes MGMT and MLH1 in osteoblasts, resulting in cell proliferation and activation and causing the development of skeletal fluorosis.

MicroRNA expression patterns of the kidney in hyperuricemia mice treated with Xiezhuo Chubi Decoction.

OBJECTIVE: To investigate the effects of Xiezhuo Chubi Decoction (XZCBD) on the microRNA expression patterns of kidney in mice with hyperuricemia. METHODS: Sixty Kunming male mice were randomly divided into the high-, medium-, and low-dose XZCBD groups, benzbromarone group, model group, and control group. Except the control group, all mice were established with yeast method combined with uricase inhibition method to build hyperuricemia model, and the corresponding drugs (37.5 g/kg, 18.75 g/kg, 9.375 g/kg, and 0.02 g/kg per day) were administrated on the 7th day. On the 22nd day, the blood uric acid concentration was detected, and microRNA with obvious changes in kidney was screened with qRT-PCR. RESULTS: The uric acid in the model group was higher than that in the control group, and the levels of the uric acid were reduced after being treated with XZCBD; the differences among groups were significant (P<0.05). Compared with the control group, 32 kinds of microRNA expression changes were detected on the 15th day after being treated with high-dose XZCBD by microRNA expression profile screening. Among them, miR-34a could inhibit the expression of human urate anion exthanger 1, and miR-146a might have inhibited the inflammatory reaction. CONCLUSION: XZCBD could significantly reduce the serum uric acid level; its effect on hyperuricemia might be through affecting microRNA expressions.