The application of virtual reality meditation and mind-body exercises among older adults.

Virtual reality (VR)-based mindfulness is a promising method to improve the health of older adults. Therefore, many attempts have been made to explore the application of VR-based mindfulness, such as VR meditation and mind-body exercises, in older adults. Generally, current studies indicate the heavy reliance on apparatus for implementing VR-based mindfulness interventions. In VR meditation, the crucial apparatus is VR headsets. In VR mind-body exercises, three essential components are required: motion capture sensors, main consoles, and display screens. In the aspect of health promotion, VR meditation is an effective method for improving mental health, pain, and quality of life in older adults. VR mind-body exercises contribute to increasing the mental health and physical function of older adults. Furthermore, VR mind-body exercises may be combined with other forms of exercise as a mixed method to promote the health of older adults. VR-based mindfulness interventions enhance the meditation and mind-body exercises experience for older adults while improving accessibility. However, their implementation still encounters a series of challenges, such as cost, technical anxiety, and apparatus-related issues. Additionally, we recommend future research to examine the optimal exercise dose for VR mind-body exercises to maximize their health benefits.

Upregulation of miR-499a Targets Beclin1 to Modulate Astrocyte Autophagy and Promote Ischemic Stroke.

OBJECTIVE: To investigate the clinical significance of miR-499a expression in the serum of ischemic stroke patients and its potential mechanism in regulating astrocytes to promote ischemic stroke. METHODS: Serum samples from 99 ischemic stroke patients and 99 healthy individuals were collected and analyzed for miR-499a expression through RT-PCR. Statistical analysis was performed to compare the expression differences between the two groups, and correlation between miR-499a expression and clinical pathological indices in stroke patients was analyzed. MiR-499a mimic, inhibitor, and negative control vectors were constructed and transfected into astrocyte SVGp12 cells. Afterward, miR-499a expression was validated by RT-PCR, cell viability was assessed by CCK8 assay, and apoptosis was detected using flow cytometry. The binding sites of miR-499a and Beclin1 were predicted by the Target-scan database and confirmed by dual luciferase assay. After overexpressing Beclin1, co-transfection with miR-499a mimic or negative control was conducted to observe the reverse effect of miR-499a mimic on Beclin1 overexpression. RESULTS: MiR-499a was significantly upregulated in the stroke group (p<0.001), it was positively correlated with TC (Total Cholesterol), LDL-C (Low-density lipoprotein cholesterol), and APO-A1 (Apolipoprotein A1) (R2>0.3, p<0.001). MiR-499a mimics promoted cell viability while inhibiting apoptosis of astrocytes. MiR-499a targeted Beclin 1 and inhibited its mRNA and protein expression, as well as the expression of autophagy-related proteins LC-3 and p62. MiR-499a could reverse the impact of Beclin1 overexpression on SVGp12 astrocyte proliferation and apoptosis. CONCLUSION: Serum miR-499a in stroke patients may serve as a potential diagnostic indicator. MiR-499a-mediated inhibition of Beclin 1, subsequently leading to suppression of astrocytic autophagy and viability, may represent a pivotal mechanism underlying its promotion of IS.

IGFBP2 from a novel copper metabolism-associated biomarker promoted glioma progression and response to immunotherapy.

Introduction: Copper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance. Methods: To address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated. Results: Notably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.

A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer.

Bladder cancer (BLCA) is a common and difficult-to-manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA.

HABP2 Encapsulated by Peripheral Blood-Derived Exosomes Suppresses Astrocyte Autophagy to Exacerbate Neuroinflammatory Injury in Mice with Ischemic Stroke.

Exosomes are shown to be involved in the regulation of neuroinflammatory injury. The current study analyzed how peripheral blood-derived exosomes affected hyaluronan-binding protein 2 (HABP2) expression to regulate neuroinflammatory injury after ischemic stroke (IS). An IS animal model was stimulated by middle cerebral artery occlusion (MCAO), followed by injection of lentivirus. Peripheral blood samples were collected from MCAO mice after different treatments. The cerebral infarction volume, astrocyte activation, and neuroinflammation were observed by TTC staining, immunofluorescence, and ELISA, respectively. HABP2 was highly expressed in the brain tissues of MCAO mice. Also, an enhancement of HABP2 was noted in their peripheral blood-derived exosomes, while loss of HABP2 in peripheral blood-derived exosomes promoted the astrocyte autophagy and reduced the release of the inflammatory factors as well as the apoptosis of neuronal cells. PAR1 overexpression reversed the effect of HABP2 loss on autophagy and neuroinflammation in MCAO mice. Additionally, the agonist of the PI3K/AKT/mTOR pathway, SC79, could also reverse the effect of sh-PAR1 on neuroinflammation. Mechanistically, HABP2 enhanced PAR1 to activate the PI3K/AKT/mTOR pathway, thereby suppressing cell autophagy. Overall, HABP2 in peripheral blood-derived exosomes can activate the PAR1/PI3K/AKT/mTOR pathway to reduce autophagy and aggravate neuroinflammatory injury after IS.

Using structural equation modeling to explore the influences of physical activity, mental health, well-being, and loneliness on Douyin usage at bedtime.

Douyin is the Chinese version of TikTok. Using Douyin at bedtime is a very common behavior among Douyin users. However, the reasons why users like using Douyin before sleep are yet unclear. We conducted a cross-section survey from January 1st to January 16th, 2023 to capture data to examine the associations of depression, anxiety, life satisfaction, well-being, loneliness, and physical activity with Douyin usage at bedtime. The mediation role of insomnia in these associations was examined. A total of 3,392 participants who met the inclusion criteria were included for analysis. Our structural equation modeling analysis showed that depression on (ß = 0.08; p < 0.05), anxiety (ß = 0.06; p < 0.05), and loneliness (ß = 0.14; p < 0.05) were directly associated with increased Douyin usage at bedtime, and were also indirectly associated with Douyin usage through insomnia (depression: ß = 0.18; p < 0.05, anxiety: ß = 0.16; p < 0.05, and loneliness: ß = 0.12; p < 0.05). Life satisfaction (ß = -0.05; p < 0.05) and well-being (ß = -0.20; p < 0.05) were directly associated with decreased Douyin usage at bedtime, and were also indirectly associated with Douyin usage through insomnia (life satisfaction: ß = -0.09; p < 0.05, and well-being: ß = -0.11; p < 0.05). However, physical activity was unexpectedly associated with increased Douyin usage at bedtime (ß = 0.20; p < 0.05). In conclusion, our findings shed new light on the specific reasons why Douyin users like using Douyin at bedtime.

Preclinical findings: The pharmacological targets and molecular mechanisms of ferulic acid treatment for COVID-19 and osteosarcoma via targeting autophagy.

The variant virus-based 2019 coronavirus disease (COVID-19) pandemic has reportedly impacted almost all populations globally, characterized by a huge number of infected individuals. Clinical evidence proves that patients with cancer are more easily infected with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) because of immunologic deficiency. Thus, there is an urgent need to develop candidate medications to treat patients with cancer plus COVID-19, including those with osteosarcoma (OS). Ferulic acid, a latent theriacal compound that has anti-tumor and antivirus activities, is discovered to have potential pharmacological use. Thus, in this study, we aimed to screen and determine the potential therapeutic targets of ferulic acid in treating patients with OS plus COVID-19 as well as the pharmacological mechanisms. We applied a well-established integrated methodology, including network pharmacology and molecular docking technique, to detail target prediction, network construction, gene ontology, and pathway enrichment in core targets. The network pharmacology results show that all candidate genes, by targeting autophagy, were the core targets of ferulic acid in treating OS and COVID-19. Through molecular docking analysis, the signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were identified as the pharmacological targets of ferulic acid in treating OS. These preclinical findings from bioinformatics analysis altogether effectively determined the pharmacological molecules and mechanisms via targeting autophagy, demonstrating the therapeutic effectiveness of ferulic acid against COVID-19 and OS.

microRNA-93 packaged in extracellular vesicles from mesenchymal stem cells reduce neonatal hypoxic-ischemic brain injury.

OBJECTIVE: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been proposed as a promising strategy for treating ischemia-related diseases. Herein, we probed into the role of miR-93 delivered by BMSC-EVs in hypoxic-ischemic brain injury (HIBD). METHODS: Neonatal HIBD mouse models and hippocampal neuron models of oxygen glucose deprivation (OGD) were constructed. EVs were isolated from the culture medium of bone marrow MSCs (BMSCs). After co-culture of BMSC-EVs with OGD-exposed hippocampal neurons, the effect of microRNA-93 (miR-93) delivered by BMSC-EVs on OGD-induced hippocampal neurons as well as on HIBD in vivo under transfection of miR-93 mimic or inhibitor was explored. The interaction among miR-93, JMJD3, and p53/KLF2 axis was assessed. RESULTS: BMSC-EVs prevented OGD-induced hippocampal neuron apoptosis and inflammation, which was associated with their transfer of miR-93 into the hippocampal neurons. miR-93 targeted JMJD3 and downregulated its expression, thus inhibiting the OGD-induced hippocampal neuron apoptosis. By regulating the JMJD3/p53/KLF2 axis, miR-93 in BMSC-EVs reduced the OGD-induced hippocampal neuron apoptosis in vitro as well as alleviating HIBD in vivo. CONCLUSIONS: The current study highlighted that miR-93 delivered by BMSC-EVs alleviated HIBD in neonatal mice through the JMJD3-dependent p53/KLF2 axis.

miR-150-3p enhances neuroprotective effects of neural stem cell exosomes after hypoxic-ischemic brain injury by targeting CASP2.

Brains are vulnerable to ischemic/hypoxic damage, which are directly caused by stroke, hypoxic-ischemic encephalopathy and other cerebral diseases. Currently, therapeutic strategies against cerebral ischemia and hypoxia are extremely limited. Recent studies have indicated that stem cell-derived exosomes play a neuroprotective role in hypoxic-ischemic brain injury. However, the treatment mechanism remains unclear. In this study, we cultured neural stem cells (NSCs) in vitro successfully. Exosomes isolated from NSCs (NSCs-Ex) inhibited the apoptosis while promoting the proliferation of SH-SY5Y cells both in normal and oxygen-glucose deprivation (OGD) culture conditions. Moreover, in vivo studies demonstrated that NSCs-Ex significantly reduced the infarction area in the middle cerebral artery occlusion (MCAO) model and suppressed the apoptosis of neurons. Furthermore, miR-150-3p was identified as the most abundantly expressed miRNA in exosomes compared to their parent NSCs. The miR-150-3p mimic displayed neuroprotective effects while miR-150-3p inhibitor exacerbated nerve injury both in vivo and in vitro. We further identified CASP2 as a miR-150-3p target. Thus, our data indicate that NSC-Ex facilitate the neuroprotective effects via transfer of miR-150-3p which targets CASP2, thus suppressing neuronal apoptosis after brain injury. Our results suggest that NSCs-Ex prevent cerebral injury by transferring miR-150-3p which promotes neurons proliferation by inhibiting CASP2 signaling pathway.

Beclin­1 exerts protective effects against cerebral ischemia­reperfusion injury by promoting DNA damage repair through a non­autophagy­dependent regulatory mechanism.

Cerebral ischemia­reperfusion (I/R) can result in severe brain injury, for which there are no optimal treatment options. I/R is often accompanied by increased autophagy. Beclin­1, a central player in autophagy, has been extensively studied in I/R; however, to date, at least to the best of our knowledge, there are no definitive descriptions of its specific role. Thus, the aim of the present study was to explore the regulatory role played by Beclin­1 in I/R. In vivo experiments were performed using an animal model of brain I/R with male Sprague­Dawley rats. Brain tissue damage was observed using 2,3,5­triphenyltetrazolium chloride, and hematoxylin and eosin staining. Tissue apoptosis levels were evaluated using a TUNEL assay, as well as western blot analysis. Immunofluorescence together with western blot analysis was used to detect autophagy in the tissues. Immunohistochemistry and western blot analysis were used to analyze DNA double­stranded breaks (DSBs). Moreover, HT22 cells overexpressing Beclin­1 were subjected to oxygen glucose deprivation/reoxygenation injury to simulate I/R pathological damage in vitro. Apoptosis was assessed using TUNEL and flow cytometric assays in this in vitro model, and autophagy was assessed using immunofluorescence and western blot analysis. The DSBs of the cells were analyzed using western blot analysis. I/R activated autophagy and induced DSBs. Autophagy inhibitors decreased brain tissue damage and reduced cell apoptosis; however, the degree of decrease in damage and apoptosis was not highly associated with the change in autophagy, and the frequency of DSBs slightly increased. The overexpression of Beclin­1 in neurons significantly attenuated I/R­induced damage and promoted DSB repair. On the whole, the present study demonstrates that Beclin­1 protects neurons from ischemic damage through the non­autophagy­dependent regulation of DNA repair processes.

Knockdown of RNF183 suppressed proliferation of lung adenocarcinoma cells via inactivating the STAT3 signaling pathway.

Proteins of the RNF183 (RING finger 183) family proteins have been reported to be of great importance in tumor the initiation and progression. However, the biological role and regulatory mechanism of RNF183 in non small cell lung cancer (NSCLC) development and progression are poorly defined. Hence, lung adenocarcinoma (LUAD) cell proliferation, cell apoptosis and cell cycle were measured using Cell Counting Kit-8 and flow cytometry analysis, respectively. The correlation between RNF183 and SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase) was measured using coimmunoprecipitation and ubiquitination analysis in vitro. Tumor growth of NSCLC cells in vivo was measured using the nude mouse xenograft model. In this study, we verify that elevated RNF183 expression in tumor tissues of LUAD, origin from the TCGA, GEPIA, TIMER, and UALCAN database. RNF183 regulates apoptosis and cell cycle in vitro and tumor growth in vivo by activating the STAT3 pathway through ubiquitination of SHP2, a negative feedback regulator of the STAT3 pathway. Taken together, our results demonstrate that RNF183 regulates proliferation, apoptosis, and cell cycle in LUAD cells via modulation of SHP2/STAT3 signaling, suggesting the potential for targeting the RNF183-SHP2/STAT3 pathway for use in LUAD treatment.

[miR-146a-3p is down-regulated and IL-17 is up-regulated in peripheral blood CD4+ T cells of children with neonatal sepsis].

Objective To investigate the expression of microRNA-146a-3p(miR-146a-3p) and interleukin 17 (IL-17) in peripheral blood CD4+ T cells of neonates with sepsis (NS) and its regulation mechanism. Methods The expression of miR-146a-3p and IL-17 mRNA in CD4+ T cells of 66 children with sepsis (septicemia group), 40 children with infectious diseases (infection group), and 40 healthy newborns (control group) were detected by real-time quantitative PCR, and the level of IL-17 in peripheral blood was detected by ELISA. The targeting effect of the miR-146a-3p on IL-17 was verified by the dual luciferase reporter assay. After isolation of the CD4+ T cells, the expression of miR-146a-3p in CD4+ T cells was promoted or inhibited by miR-146a-3p mimic or miR-146a-3p inhibitor. The proportion of Th17 cells was detected by flow cytometry, and the methylation of miR-146a-3p gene was detected by methylation specific PCR. The changes of Th17 cell proportion and IL-17 expression were observed after adding methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) to CD4+ T cells. Results Compared with those in the infection group and the control group, the expression of miR-146a-3p in peripheral blood CD4+ T cells decreased, while the expression of IL-17 mRNA and the level of IL-17 in peripheral blood increased in septicemia group. Transfection of miR-146a-3p mimic in CD4+ T cells significantly inhibited the activity of wild-type luciferase in the 3'UTR of IL-17. After transfection of miR-146a-3p mimic, the expression of IL-17 mRNA in CD4+ T cells, and the level of IL-17 and the proportion of Th17 cells in the supernatant were significantly decreased. After transfection of miR-146a-3p inhibitor, the expression of IL-17 mRNA, and the level of IL-17 and the proportion of Th17 cells in the supernatant were increased. The methylation rate of miR-146a-3p gene promoter in the peripheral blood of the septicemia group was significantly higher than those of the control group and the infection group. After the addition of 5-Aza-dC in CD4+ T cells, the expression of miR-146a-3p was increased and the expression of IL-17 mRNA was decreased, and in the supernatant, the level of IL-17 was decreased and the proportion of Th17 cells was significantly reduced. Conclusion The expression of miR-146a-3p is down-regulated and the expression of IL-17 is up-regulated in peripheral blood CD4+ T cells of children with neonatal sepsis.

circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway.

Glioblastoma has been identified as the most common and aggressive primary brain tumor in adults. Recently, it has been found that cisplatin (DDP) treatment is a common chemotherapeutic method for GBM patients. circ_PTN (ID number: hsa_circ_0003949) is a newly found circular (circRNA) which has been proved to be highly expressed in GBM cells, while its role in GBM remains unclear. Therefore, our study focused on investigating the role of circ_PTN in the DDP resistance of GBM cells. The expression of circ_PTN in DDP-sensitive and DDP-resistant GBM cells was detected in our assay. Functional experiments were utilized to unveil the effects of circ_PTN on the DDP resistance of GBM cells. Moreover, mechanism assays were conducted to confirm the mechanism of how circ_PTN affected the DDP resistance of GBM cells. According to the results, we found that circ_PTN promoted the DDP resistance of GBM cells through activation of the PI3K/AKT pathway. Moreover, circ_PTN silencing inhibited the DDP resistance of GBM tumors in vivo. To conclude, our study unveiled the influence of circ_PTN on the DDP resistance of GBM cells, which might provide a therapeutic target for GBM treatment via DDP.

NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.

The prognosis of glioma is poor as its pathogenesis and mechanisms underlying cisplatin chemoresistance remain unclear. Nucleosome assembly protein 1 like 1 (NAP1L1) is regarded as a hallmark of malignant tumors. However, the role of NAP1L1 in glioma remains unknown. In this study, we aimed to investigate the molecular functions of NAP1L1 in glioma and its involvement in cisplatin chemoresistance, if any. NAP1L1 was found to be upregulated in samples from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry indicated that NAP1L1 and hepatoma-derived growth factor (HDGF) were enhanced in glioma as compared to the para-tumor tissues. High expressions of NAP1L1 and HDGF were positively correlated with the WHO grade, KPS, Ki-67 index, and recurrence. Moreover, NAP1L1 expression was also positively correlated with the HDGF expression in glioma tissues. Functional studies suggested that knocking down NAP1L1 could significantly inhibit glioma cell proliferation both in vitro and in vivo, as well as enhance the sensitivity of glioma cells to cisplatin (cDDP) in vitro. Mechanistically, NAP1L1 could interact with HDGF at the protein level and they co-localize in the cytoplasm. HDGF knockdown in NAP1L1-overexpressing glioma cells significantly inhibited cell proliferation. Furthermore, HDGF could interact with c-Jun, an oncogenic transcription factor, which eventually induced the expressions of cell cycle promoters, CCND1/CDK4/CDK6. This finding suggested that NAP1L1 could interact with HDGF, and the latter recruited c-Jun, a key oncogenic transcription factor, that further induced CCND1/CDK4/CDK6 expression, thereby promoting proliferation and chemoresistance in glioma cells. High expression of NAP1L1 in glioma tissues indicated shorter overall survival in glioma patients.

Associations of serum estradiol level, serum estrogen receptor-alpha level, and estrogen receptor-alpha polymorphism with male infertility: A retrospective study.

ABSTRACT: Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ±â€Š35.3 vs 129.62 ±â€Š49.11 pg/mL, P < .05) and ESRα (3.02 ±â€Š2.62 vs 1.33 ±â€Š0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.

CCT5 interacts with cyclin D1 promoting lung adenocarcinoma cell migration and invasion.

Cyclin D1 (CCND1) has been identified as a metastatic promoter in various tumors including lung adenocarcinoma (LUAD), a subtype of non small cell lung cancer (NSCLC). The previous observation revealed that CCND1 was upregulated in NSCLC and predicted poor prognosis of LUAD patients. In this study, we examined a chaperonin containing TCP1 subunit 5 (CCT5) protein interacts with CCND1 in LUAD. Immunofluorescence demonstrated the co-localization of CCT5 and CCND1 protein in LUAD cells. CCT5 expression was detected with both immunohistochemistry (IHC) and bioinformatics analyses. Similar with the expression pattern of CCND1, CCT5 displayed a high level in LUAD tissues compared to non cancerous lung specimens. Patients with high CCT5 expression showed a significant shorter overall survival relative to those with low expression level. Furthermore, upregulated CCT5 exhibited significant positive correlation with TNM stage of LUAD patients in both IHC analyses and bioinformatics. Knocking down CCT5 remarkably inhibited LUAD cell migration and invasion in vitro by inactivating PI3K/AKT and its downstream EMT signals, which could abrogated the accelerated migration and invasion caused by CCND1 overexpression. In summary, our study discovered a highly expressed protein CCT5 in LUAD which interacted with CCND1 and promoted migration and invasion of LUAD cells by positively moderating PI3K/AKT-induced EMT pathway.

Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population.

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.

LncRNA LL22NC03-N14H11.1 promoted hepatocellular carcinoma progression through activating MAPK pathway to induce mitochondrial fission.

Involvement of long non-coding RNAs (lncRNAs) in hepatocarcinogenesis has been largely documented. Mitochondrial dynamics is identified to impact survival and metastasis in tumors including hepatocellular carcinoma (HCC), but the underlying mechanism remains poorly understood. This study planned to explore the regulation of lncRNA LL22NC03-N14H11.1 on HCC progression and mitochondrial fission. Dysregulated lncRNAs in HCC are identified through circlncRNAnet and GEPIA bioinformatics tools. Biological function of LL22NC03-N14H11.1 in HCC was detected by CCK-8 assay, flow cytometry analysis, transwell invasion, and wound healing assays. Molecular interactions were determined by RNA immunoprecipitation, RNA pull-down, and co-immunoprecipitation assays. Results showed that LL22NC03-N14H11.1 was upregulated in HCC tissues and cells. Functionally, LL22NC03-N14H11.1 contributed to cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in HCC. Moreover, LL22NC03-N14H11.1 facilitated mitochondrial fission in HCC cells. Mechanistically, LL22NC03-N14H11.1 recruited Myb proto-oncogene (c-Myb) to repress the transcription of leucine zipper-like transcription regulator 1 (LZTR1), so as to inhibit LZTR1-mediated ubiquitination of H-RAS (G12V), leading to the activation of mitogen-activated protein kinase (MAPK) signaling and induction of p-DRP1 (Serine 616). In conclusion, this study firstly revealed that lncRNA LL22NC03-N14H11.1 promoted HCC progression through activating H-RAS/MAPK pathway to induce mitochondrial fission, indicating LL22NC03-N14H11.1 as a novel potential biomarker for HCC treatment.

Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke.

Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of MEG3 (maternally expressed gene 3), microRNA-378 (miR-378), and GRB2 (growth factor receptor-bound protein 2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded-induced ischemic stroke and an in vitro model of oxygen-glucose deprivation-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blotting analysis, and neuron death was evaluated using a lactate dehydrogenase leakage rate test. First, it was found that the GRB2 gene, up-regulated in middle cerebral artery occluded-operated mice and oxygen-glucose deprivation-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice, as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

Upregulation of DEAD box helicase 5 and 17 are correlated with the progression and poor prognosis in gliomas.

Recent researches indicated Ddx5 and Ddx17 play crucial roles in tumorigenesis. However, the study of Ddx5 and Ddx17 in glioma remains a little. Our study investigated their expression in glioma and evaluated its association with clinical factors and prognostic significance. The expression of Ddx5 and Ddx17 were both upregulated in glioma tissues compared to normal brain tissues, and a significant positive correlation between Ddx5 and Ddx17 expression was identified by statistical analysis. Immunohistochemical staining verified the expression of Ddx5 and Ddx17 in peritumoral zone was lower than that in core zone but higher than normal brain tissues. Moreover, the increased expression of Ddx5 and Ddx17 was markedly correlated with WHO Grade and histological type, and high Ddx5 and Ddx17 were found to be significantly associated with the worse overall survival of glioma patients. In additional, higher expression of both Ddx5 and Ddx17 predicted shorter clinical survival time for high-grade glioma patients with radiotherapy or with chemotherapy. In conclusion, overexpressed Ddx5 and Ddx17 are involved in the clinical progression and poor prognosis of glioma patients, suggesting that their upregulation can be used as a reliable clinical predictor for tumor diagnosis and to predict survival in patients with glioma.