Gestational organophosphate esters (OPEs) exposure in association with placental DNA methylation levels of peroxisome proliferator-activated receptors (PPARs) signaling pathway-related genes.

BACKGROUND: Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. OBJECTIVES: Based on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth. METHODS: We measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth. RESULTS: We observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation. CONCLUSIONS: Gestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.

The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study.

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children's digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

Increasing Hybrid Rice Yield, Water Productivity, and Nitrogen Use Efficiency: Optimization Strategies for Irrigation and Fertilizer Management.

Water and fertilizer are crucial in rice growth, with irrigation and fertilizer management exhibiting synergies. In a two-year field study conducted in Yiyang City, Hunan Province, we examined the impact of three irrigation strategies-wet-shallow irrigation (W1), flooding irrigation (W2), and the "thin, shallow, wet, dry irrigation" method (W3)-in combination with distinct fertilizer treatments (labeled F1, F2, F3, and F4, with nitrogen application rates of 0, 180, 225, and 270 kg ha-1, respectively) on rice yield generation and water-fertilizer utilization patterns. The study employed Hybrid Rice Xin Xiang Liang you 1751 (XXLY1751) and Yue Liang you Mei Xiang Xin Zhan (YLYMXXZ) as representative rice cultivars. Key findings from the research include water, fertilizer, variety, and year treatments, which all significantly influenced the yield components of rice. Compared to W2, W1 in 2022 reduced the amount of irrigation water by 35.2%, resulting in a 42.0~42.8% increase in irrigation water productivity and a 25.7~25.9% increase in total water productivity. In 2023, similar improvements were seen. Specifically, compared with other treatments, the W1F3 treatment increased nitrogen uptake and harvest index by 1.4-7.7% and 5.9-7.7%, respectively. Phosphorus and potassium uptake also improved. The W1 treatment enhanced the uptake, accumulation, and translocation of nitrogen, phosphorus, and potassium nutrients throughout the rice growth cycle, increasing nutrient levels in the grains. When paired with the F3 fertilization approach, W1 treatment boosted yields and improved nutrient use efficiency. Consequently, combining W1 and F3 treatment emerged as this study's optimal water-fertilizer management approach. By harnessing the combined effects of water and fertilizer management, we can ensure efficient resource utilization and maximize the productive potential of rice.

MiR-3074-5p suppresses non-small cell lung cancer progression by targeting the YWHAZ/Hsp27 axis.

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

Epigenetic editing of BRCA1 promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells.

Drug resistance is the primary contributor to the high mortality rate of ovarian cancer (OC). The loss of BRCA1/2 function is linked to drug sensitivity in OC cells. The aim of this study is to enhance the drug sensitivity of OC cells by inducing BRCA1 dysfunction through promoter epigenetic editing. Epigenetic regulatory regions within the BRCA1 promoter, affecting gene expression, were initially discerned through analysis of clinical samples. Subsequently, we designed and rigorously validated epigenetic editing tools. Ultimately, we evaluated the cisplatin and olaparib sensitivity of the OC cells after editing. The BRCA1 promoter contains two CpG-rich regions, with methylation of the region covering the transcription start site (TSS) strongly correlating with transcription and influencing OC development, prognosis, and homologous recombination (HR) defects. Targeting this region in OC cells using our designed epigenetic editing tools led to substantial and persistent DNA methylation changes, accompanied by significant reductions in H3K27ac histone modifications. This resulted in a notable suppression of BRCA1 expression and a decrease in HR repair capacity. Consequently, edited OC cells exhibited heightened sensitivity to cisplatin and olaparib, leading to increased apoptosis rates. Epigenetic inactivation of the BRCA1 promoter can enhance cisplatin and olaparib sensitivity of OC cells through a reduction in HR repair capacity, indicating the potential utility of epigenetic editing technology in sensitization therapy for OC.

Low-frequency rTMS modulated the excitability and high-frequency firing in hippocampal neurons of the Alzheimer's disease mouse model.

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, holds potential for applications in the treatment of Alzheimer's disease (AD). This study aims to compare the therapeutic effects of rTMS at different frequencies on Alzheimer's disease and explore the alterations in neuronal electrophysiological properties throughout this process. APP/PS1 AD mice were subjected to two rTMS treatments at 0.5 Hz and 20 Hz, followed by assessments of therapeutic outcomes through the Novel Object Recognition (NOR) and Morris Water Maze (MWM) tests. Following this, whole-cell patch-clamp techniques were used to record action potential, voltage-gated sodium channel currents, and voltage-gated potassium channel currents in dentate gyrus granule neurons. The results show that AD mice exhibit significant cognitive decline compared to normal mice, along with a pronounced reduction in neuronal excitability and ion channel activity. Both frequencies of rTMS treatment partially reversed these changes, demonstrating similar therapeutic efficacy. Furthermore, the investigation indicates that low-frequency magnetic stimulation inhibited the concentrated firing of early action potentials in AD.

[The inverse stochastic resonance in a small-world neuronal network under electromagnetic stimulation].

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.

Exosome-delivered circRPS5 inhibits the progression of melanoma via regulating the miR-151a/NPTX1 axis.

BACKGROUND: Circular RNAs (circRNAs) have been reported to exert critical functions in tumorigenesis and development. However, the underlying mechanism by which circRNAs regulate melanoma progression remain to be elucidated. METHODS: The differentially expressed circRNAs were first identified by circRNA-seq, and circRNAs were validated via qRT-PCR and Sanger sequencing. Then, the impact of circRPS5, miR-151a and NPTX1 expression on the progression of melanoma cell were determined by gain- and loss-of-function assays. The relationship between circRPS5, miR-151a, and NPTX1 was predicted by StarBase website and authenticated by luciferase reporter assay. The melanoma cells-derived exosomes were characterized using nanoparticle tracking analysis (NTA) and western blot. RESULTS: CircRPS5 was significantly downregulated in melanoma tissues and cell lines. Functionally, circRPS5 suppressed the proliferation, migration, and invasion of melanoma cells, and induced cell cycle arrest and apoptosis in vitro. Mechanistically, circRPS5 harbor miR-151a, acting as miRNA sponge, and then miR-151a targeted the 3'-UTR of NPTX1. Finally, circRPS5 was mainly incorporated into exosomes to inhibit the progression of melanoma cells. CONCLUSIONS: This finding reveal circRPS5 suppressed the progression of melanoma through miR-151a/NPTX1 pathway, and may provide a promising therapeutic strategies for melanoma.

External Z-plasty Technique for Correction of Alar Retraction in Asian Patients.

BACKGROUND: Current strategies for correcting alar retraction mainly include cartilage grafting and composite grafting, which are relatively complicated and may produce injury to the donor site. Herein, we introduce a simple and effective external Z-plasty technique for correcting alar retraction in Asian patients with poor skin malleability. METHODS: Twenty-three patients were presented with alar retraction and poor skin malleability, and they were very concerned about the shape of the nose. These patients undergoing external Z-plasty surgery were analyzed retrospectively. In this surgery, no grafts were needed, and the location of the Z-plasty was according to the highest point of the retracted alar rim. We reviewed the clinical medical notes and photographs. During the postoperative follow-up period, patients' reported satisfaction with aesthetic outcome were also evaluated. RESULTS: The alar retraction of all the patients was successfully corrected. The postoperative mean follow-up period was 8 months (range: 5-28 mo). No incidents of flap loss, recurrence of alar retraction, or nasal obstruction were observed during postoperative follow-up. Within postoperative 3-8 weeks, minor red scarring was visible at the operative incisions in most patients. However, these scars turned unobvious after postoperative 6 months. There were 15 cases (15/23) being very satisfied with the aesthetic outcome of this procedure. Seven patients (7/23) were satisfied with the effect and the invisible scar of this operation. Only one patient was dissatisfied with the scar, but she was satisfied with the correction effect of the retraction. CONCLUSION: This external Z-plasty technique can be an alternative method for correction of alar retraction with no need of cartilage grafting, and the scar can be unobvious with fine surgical suture. However, the indications should be limited in patients with severe alar retraction and poor skin malleability, who should not particularly care about the scars.

Repetitive transcranial magnetic stimulation enhances the neuronal excitability of mice by regulating dynamic characteristics of Granule cells' Ion channels.

This study aims to explore the effects of acute high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) on neuronal excitability of granule cells in the hippocampal dentate gyrus, as well as the underlying intrinsic mediating mechanisms by which rTMS regulates neuronal excitability. First, high-frequency single TMS was used to measure the motor threshold (MT) of mice. Then, rTMS with different intensities of 0 MT (control), 0.8 MT, and 1.2 MT were applied to acute mice brain slices. Next, patch-clamp technique was used to record the resting membrane potential and evoked nerve discharge of granule cells, as well as the voltage-gated sodium current (I Na) of voltage-gated sodium channels (VGSCs), transient outward potassium current (I A) and delayed rectifier potassium current (I K) of voltage-gated potassium channels (Kv). Results showed that acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly activated I Na and inhibited I A and I K compared with control group, due to the changes of dynamic characteristics of VGSCs and Kv. Acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly increased membrane potential and nerve discharge frequency. Therefore, changing dynamic characteristics of VGSCs and Kv, activating I Na and inhibiting I A and I K might be one of the intrinsic mediating mechanisms by which rTMS enhanced the neuronal excitability of granular cells, and this regulatory effect increased with the increase of stimulus intensity.

[Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice].

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Ultra-minimal pinhole blepharoplasty: A minimally invasive technique for the correction of eyelid bags.

OBJECTIVE: The aim of the study was to investigate the efficacy and complications of ultra-minimal pinhole blepharoplasty in the treatment of eyelid bags. METHODS: This retrospective study included patients with eyelid bags treated using a minimally invasive blepharoplasty technique between May 2018 and June 2021. The postoperative course and complications and patient satisfaction were analyzed. RESULTS: A total of 460 patients (136 males and 324 females) were included with a mean age of 42.12 ± 9.76 years. The mean operative time was 24.3 min. After the operation, the patients had no infection, numbness, or lower eyelid varus, valgus, or withdrawal. Nine patients developed transient binocular diplopia, which disappeared 0.5-1 h after surgery. Two patients developed chemosis, which disappeared after therapy. Six months after the operation, 440 (95.65%) patients were satisfied with improvement in their fat bulge. A total of 434 (94.78%) patients were satisfied with improvement in their tear groove. CONCLUSION: Ultra-minimal pinhole blepharoplasty is a safe, effective, and minimally invasive treatment for eyelid bags.

Research on intelligent analysis strategies to improve athletes' psychological experience in the era of artificial intelligence.

In order to improve the psychological quality of athletes, this paper combines artificial intelligence technology to quantitatively analyze the psychological experience of athletes. Moreover, in view of the insufficiency of the ASI method to standardize the data, this study proposes to use the normalization method for processing. In addition, in order to verify the feasibility and effectiveness of the research and development of the multi-dimensional dual-objective CD-CAT topic selection strategy, this paper adopts the Monte Carlo simulation experiment method to analyze the data. Finally, this paper constructs an analysis system of athlete's psychological experience and intelligent decision-making based on artificial intelligence. The experimental data analysis results show that the intelligent decision-making system based on artificial intelligence for athletes' psychological experience proposed in this paper has a good effect and can effectively promote the psychological training effect of athletes.

Value of M2BP in predicting in-stent restenosis in patients after coronary drug-eluting stent implantation.

OBJECTIVE: We evaluated the association between plasma levels of mac-2 binding protein (M2BP) with the risk of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). METHODS: Plasma M2BP levels were compared between 258 patients who experienced ISR at 12-months post-PCI and 258 patients, matched for age and sex, without angiographic evidence of ISR. RESULTS: The plasma M2BP level was significantly higher in the ISR than in the non-ISR group. On multivariate analysis, adjusted for potential clinical, biochemical, and angiography characteristics, M2BP remained as an independent significant predictor of ISR. CONCLUSIONS: M2BP may be an important predictive biomarker of ISR and may be useful in identifying at-risk patients.

Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study.

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180 s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6 months and ≥6 months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Case report: Treatment of a patient with STEMI and cardiogenic shock caused by RCA originating from LAD.

The right coronary artery (RCA) originating from the left anterior descending artery (LAD) is a very rare variation of coronary artery anomaly. This kind of anomaly is usually considered to be clinically benign. Here, we present an acute myocardial infarction patient with a single coronary artery (SCA), in whom the LAD and RCA are both occlusive at the same time. He suffered from ventricular fibrillation, cardiogenic shock, and severe bradyarrhythmias many times. Fortunately, this patient survived from death through our effective medical procedures.

[Research progress on the effect of transcranial magnetic stimulation on learning, memory and plasticity of brain synaptic].

Transcranial magnetic stimulation (TMS) as a noninvasive neuromodulation technique can improve the impairment of learning and memory caused by diseases, and the regulation of learning and memory depends on synaptic plasticity. TMS can affect plasticity of brain synaptic. This paper reviews the effects of TMS on synaptic plasticity from two aspects of structural and functional plasticity, and further reveals the mechanism of TMS from synaptic vesicles, neurotransmitters, synaptic associated proteins, brain derived neurotrophic factor and related pathways. Finally, it is found that TMS could affect neuronal morphology, glutamate receptor and neurotransmitter, and regulate the expression of synaptic associated proteins through the expression of brain derived neurotrophic factor, thus affecting the learning and memory function. This paper reviews the effects of TMS on learning, memory and plasticity of brain synaptic, which provides a reference for the study of the mechanism of TMS.

TCF21 regulates miR-10a-5p/LIN28B signaling to block the proliferation and invasion of melanoma cells.

BACKGROUND AND AIM: Some research has suggested that miRNA-10a (miR-10a-5p) had an inhibitory function in proliferation and invasion of cancers. Whereas the role of miR-10a-5p in melanoma has not been fully explored. This study aims to confirm LIN28B as the targeted gene of miR-10a-5p which was explored in melanoma cells. In addition, upstream regulatory molecule of miR-10a-5p was also investigated in melanoma cells. METHODS: Real-time Quantitative polymerase chain reaction (RT-qPCR) was adopted to analyze miR-10a-5p expression level in melanoma and the normal human epidermal melanocyte cells. Several biological assays were performed to evaluate miR-10a-5p influences on cell proliferation, migration and invasion ability in A375 and B16-F10 cells. Gene prediction of miRNA targeting and a dual luciferase assay were applied to assess miR-10a-5p-targeted LIN28B. Western blot assessed the impacts of miR-10a-5p on the protein expression of LIN28B. Western blot analyzed the TCF21 effects on the expression of LIN28B and RT-qPCR assessed the influence of TCF21 on the expression level of miRNA-10a. In addition, Chromatin Immunoprecipitation (ChIP) Assay and JASPAR databases were employed to explore the regulatory relationship between TCF21 and miR-10a-5p. RESULTS: We discovered that miR-10a-5p expression was lower in melanoma cells and high expression of miR-10a-5p suppressed the proliferation, migration and invasion abilities of melanoma cells. We also discovered that miR-10a-5p targeted the LIN28B mRNA 3'UTR area and diminished LIN28B protein expression. We found that LIN28B expression was strongly decreased by TCF21 upregulation in the two melanoma cells. The qRT-PCR assay showed that miR-10a-5p expression level was obviously boosted by increased TCF21 expression. The results also demonstrated that TCF21 directly regulated miR-10a-5p at transcript levels. CONCLUSION: TCF21 induced miRNA-10a targeting LIN28B could affect the progression and growth of melanoma.

Anti-inflammatory effects of miR-150 are associated with the downregulation of STAT1 in macrophages following lipopolysaccharide treatment.

Sepsis is a condition that is associated with high rates of mortality. It is characterized by serious systemic inflammatory responses induced by pathogenic invasion. Although microRNA-150 (miR-150) has been previously reported to be involved in the modulation of sepsis, the underlying molecular mechanism in sepsis remains poorly understood. In the present study, the human monocytic cell line THP-1 was treated with LPS to mimic sepsis in vitro, following which miR-150 and STAT1 expression were measured using reverse transcription-quantitative PCR or western blotting. Secretion of inflammatory cytokines interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) into the medium were measured by ELISA. The potential relationship between STAT1 and miR-150 was determined using dual-luciferase reporter and RNA immunoprecipitation assays. miR-150 expression was found to be was downregulated by LPS treatment in THP-1 cells in both dose- and time-dependent manners. LPS treatment also induced IL-1ß, IL-6 and TNF-α secretion in a manner that could be inhibited by miR-150 overexpression and enhanced by transfection with the miR-150 inhibitor. miR-150 was revealed to directly target STAT1 by negatively regulating its expression. In addition, STAT1 expression was demonstrated to be upregulated by LPS treatment. STAT1 overexpression reversed the inhibitory effects of miR-150 overexpression on IL-1ß, IL-6 and TNF-α secretion whilst STAT1 knockdown attenuated IL-1ß, IL-6 and TNF-α secretion induced by miR-150 inhibitor transfection. In conclusion, the present study suggested that miR-150 regulates the inflammatory response in macrophages following LPS challenge by regulating the expression of STAT1.