Rocuronium bromide suppresses esophageal cancer via blocking the secretion of C-X-C motif chemokine ligand 12 from cancer associated fibroblasts.

BACKGROUND: Cancer associated fibroblasts (CAFs) communicate metabolically with tumor genesis and development. Rocuronium bromide (RB) is reported to exert certain inhibitory effect on tumor. Here, we investigate the role of RB in esophageal cancer (EC) malignant progression. METHODS: Tumor xenograft models with EC cells were locally and systemically administrated with RB to detect the influence of different administrations on tumor progression. Mouse CAFs PDGFRα+/F4/80- were sorted by Flow cytometry with specific antibodies. CAFs were treated with RB and co-cultured with EC cells. The proliferation, invasion and apoptosis assays of EC cells were performed to detect the influences of RB targeting CAFs on EC cell malignant progression. Human fibroblasts were employed to perform these detections to confirm RB indirect effect on EC cells. The gene expression changes of CAFs response to RB treatment were detected using RNA sequencing and verified by Western blot, immunohistochemistry and ELISA. RESULTS: Tumors in xenograft mice were observed significantly inhibited by local RB administration, but not by systemic administration. Moreover EC cells did not show obvious change in viability when direct stimulated with RB in vitro. However, when CAFs treated with RB were co-cultured with EC cells, obvious suppressions were observed in EC cell malignancy, including proliferation, invasion and apoptosis. Human fibroblasts were employed to perform these assays and similar results were obtained. RNA sequencing data of human fibroblast treated with RB, and Western blot, immunohistochemistry and ELISA results all showed that CXCL12 expression was significantly diminished in vivo and in vitro by RB. EC cells direct treated with CXCL12 showed much higher malignancy. Moreover cell autophagy and PI3K/AKT/mTOR signaling pathway in CAFs were both suppressed by RB which can be reversed by Rapamycin pretreatment. CONCLUSIONS: Our data suggest that RB could repress PI3K/AKT/mTOR signaling pathway and autophagy to block the CXCL12 expression in CAFs, thereby weakening the CXCL12-mediated EC tumor progression. Our data provide a novel insight into the underlying mechanism of RB inhibiting EC, and emphasize the importance of tumor microenvironment (cytokines from CAFs) in modulating cancer malignant progression.

Gene expression changes reveal the impact of the space environment on the skin of International Space Station astronauts.

BACKGROUND: The various types of ionizing radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases, affecting the status of the aviators to fly. Therefore, it is important to explore the molecular-level changes in the skin during space missions. OBJECTIVES: Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression before, during and after space missions. METHODS: First, STEM (Short Time-series Expression Miner) software was used to identify the expression patterns of hair follicle genes of astronauts pre-, in- and postflight. Gene Ontology Enrichment Analysis was then performed to explore the gene functions within the module. Protein-protein interaction network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB (Molecular Signatures Database). RESULTS: Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared with preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered on return to the ground, but there are a small number of genes whose expression cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression on entry into space and decreased expression on return to Earth. The genes of this expression pattern were associated with skin development, keratinocyte differentiation and cornification. Ten hub genes were identified as skin-related genes within the module, as well as nine transcription factors and three circadian genes. One hundred and seventy-nine genes decreased in expression after entry into space and increased on return to Earth. By reviewing the literature, we found that four of the genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases. CONCLUSIONS: Through bioinformatics analysis, we found that the space environment affects skin keratinocyte differentiation, leading to skin barrier damage and inflammatory responses, and that this effect was decreased after return to Earth.

Impact of posttranslational modifications in pancreatic carcinogenesis and treatments.

Pancreatic cancer (PC) is a highly aggressive cancer, with a 9% 5-year survival rate and a high risk of recurrence. In part, this is because PC is composed of heterogeneous subgroups with different biological and functional characteristics and personalized anticancer treatments are required. Posttranslational modifications (PTMs) play an important role in modifying protein functions/roles and are required for the maintenance of cell viability and biological processes; thus, their dysregulation can lead to disease. Different types of PTMs increase the functional diversity of the proteome, which subsequently influences most aspects of normal cell biology or pathogenesis. This review primarily focuses on ubiquitination, SUMOylation, and NEDDylation, as well as the current understanding of their roles and molecular mechanisms in pancreatic carcinogenesis. Additionally, we briefly summarize studies and clinical trials on PC treatments to advance our knowledge of drugs available to target the ubiquitination, SUMOylation, and NEDDylation PTM types. Further investigation of PTMs could be a critical field of study in relation to PC, as they have been implicated in the initiation and progression of many other types of cancer.

Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications.

Both hereditary and sporadic breast cancer are suggested to develop from a stem cell subcomponent retaining most key stem cell properties but with dysregulation of self-renewal pathways, which drives tumorigenic differentiation and cellular heterogeneity. Cancer stem cells (CSCs), characterized by their self-renewal and differentiation potential, have been reported to contribute to chemo-/radio-resistance and tumor initiation and to be the main reason for the failure of current therapies in breast cancer and other CSC-bearing cancers. Thus, CSC-targeted therapies, such as those inducing CSC apoptosis and differentiation, inhibiting CSC self-renewal and division, and targeting the CSC niche to combat CSC activity, are needed and may become an important component of multimodal treatment. To date, the understanding of breast cancer has been extended by advances in CSC biology, providing more accurate prognostic and predictive information upon diagnosis. Recent improvements have enhanced the prospect of targeting breast cancer stem cells (BCSCs), which has shown promise for increasing the breast cancer remission rate. However, targeted therapy for breast cancer remains challenging due to tumor heterogeneity. One major challenge is determining the CSC properties that can be exploited as therapeutic targets. Another challenge is identifying suitable BCSC biomarkers to assess the efficacy of novel BCSC-targeted therapies. This review focuses mainly on the characteristics of BCSCs and the roles of BCSCs in the formation, maintenance and recurrence of breast cancer; self-renewal signaling pathways in BCSCs; the BCSC microenvironment; potential therapeutic targets related to BCSCs; and current therapies and clinical trials targeting BCSCs.

Human Schlafen 5 regulates reversible epithelial and mesenchymal transitions in breast cancer by suppression of ZEB1 transcription.

BACKGROUND: Human Schlafen 5 (SLFN5) has been reported to inhibit or promote cell invasion in tumours depending on their origin. However, its role in breast cancer (BRCA) is undetermined. METHODS: Differential expression analyses using The Cancer Genome Atlas (TCGA) data, clinical samples and cell lines were performed. Lentiviral knockdown and overexpression experiments were performed to detect changes in cell morphology, molecular markers and invasion. Chromatin immunoprecipitation-sequencing (ChIP-Seq) and luciferase reporter assays were performed to detect the SLFN5-binding motif. RESULTS: TCGA, clinical samples and cell lines showed that SLFN5 expression was negatively correlated with BRCA metastasis. SLFN5 knockdown induced epithelial-mesenchymal transition (EMT) and enhanced invasion in BRCA cell lines. However, overexpression triggered mesenchymal-epithelial transition (MET). SLFN5 inhibited the expression of ZEB1 but not ZEB2, SNAI1, SNAI2, TWIST1 or TWIST2. Knockdown and overexpression of ZEB1 indicated that it was a mediator of the SLFN5-governed phenotype and invasion changes. Moreover, SLFN5 inhibited ZEB1 transcription by directly binding to the SLFN5-binding motif on the ZEB1 promoter, but a SLFN5 C-terminal deletion mutant did not. CONCLUSION: SLFN5 regulates reversible epithelial and mesenchymal transitions, and inhibits BRCA metastasis by suppression of ZEB1 transcription, suggesting that SLFN5 could be a potential target for BRCA therapy.

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis.

Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 µg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA.

Identification of mitochondrial-related genes as potential biomarkers for the subtyping and prediction of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder prevalent among older adults. Although AD symptoms can be managed through certain treatments, advancing the understanding of underlying disease mechanisms and developing effective therapies is critical. Methods: In this study, we systematically analyzed transcriptome data from temporal lobes of healthy individuals and patients with AD to investigate the relationship between AD and mitochondrial autophagy. Machine learning algorithms were used to identify six genes-FUNDC1, MAP1LC3A, CSNK2A1, VDAC1, CSNK2B, and ATG5-for the construction of an AD prediction model. Furthermore, AD was categorized into three subtypes through consensus clustering analysis. Results: The identified genes are closely linked to the onset and progression of AD and can serve as reliable biomarkers. The differences in gene expression, clinical features, immune infiltration, and pathway enrichment were examined among the three AD subtypes. Potential drugs for the treatment of each subtype were also identified. Discussion: The findings observed in the present study can help to deepen the understanding of the underlying disease mechanisms of AD and enable the development of precision medicine and personalized treatment approaches.

Two new constituents from the endophyte of Alternaria alternata and its anti-neuroinflammatory activity guided by molecular docking.

Two new compounds, 3-hydroxy-1-(3-hydroxy-5-methoxyphenyl)-2-methyl propan-1-one (1) and 1,2,6-trihydroxy-8-methoxy-2,3,3a,9b-tetrahydrocyclopenta[c] isochromen-5(1H)-one (2), along with nine known compounds 3-11, involving pyranones, phenylpropenoids and alkaloids, were obtained from Alternaria alternata, an endophyte isolated from Hypericum perforatum L. The structures were elucidated by extensive spectroscopic analyses, including 1D NMR, 2D NMR, HRESIMS, IR, UV spectroscopy. The absolute configuration was established via spectroscopy techniques and X-ray crystallisation method. Furthermore, guided by molecular docking, compounds 1 and 3 exhibited promising anti-neuroinflammatory activity in LPS-induced BV-2 microglial cells, with IC50 values of 0.9 ± 0.3 µM and 3.0 ± 0.4 µM respectively. Moreover, they effectively attenuated the LPS-induced elevation of NO, TNF-α, IL-6, and IL-1ß production in BV-2 microglial cells. These findings diversify the metabolite of A. alternata and highlight their potential as leading compounds against neuroinflammatory-related diseases.

Transcriptome profiling and bioinformatic analysis of the effect of ganoderic acid T prevents Sendai virus infection.

Ganoderic acid T (GA-T) is an important triterpene of Ganoderma lucidum, which is utilized to treat viral infections. Sendai virus (SeV) is widely studied to determine the molecular biological characteristics of RNA viruses and employed to elucidate the mechanisms governing the innate immune response. However, the comprehensive mechanism governing the antiviral effects of GA-T against SeV infection remains unknown. In this study, SeV-infected host cells were treated with 16.3 µM GA-T, subsequently RNA-seq analysis was performed to screen the differentially expressed genes (DEGs). The RNA-seq data showed that GA-T treatment upregulated 934 DEGs and downregulated 1283 DEGs against viral infection, in particularly, IFNGR1, IL1A, and IL1R1 were upregulated, and mTOR, SMAD3, IFNL2 and IFNL3 were decreased. GO and KEGG analysis illustrated that DEGs were clustered in mTOR and IL-17 signalling pathways. Protein-protein interaction network analysis indicated the high degree of nodes, such as CXCL8, CSF2, CXCL1 and MYD88. Our results indicated that GA-T exerted its antiviral pharmacological effects through inhibition of the mTOR signalling pathway and adjustment of innate immunity system and the inflammatory response involving the IL-17 signalling pathway. Our results may help to elucidate the potential functions and underlying mechanisms governing the antiviral effects of GA-T.

Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment.

Ganoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum. Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets several genes to prevent cancer, including colorectal cancer (CRC). Thus, we hypothesized that GA-Me might be a multitarget ligand against cancer. However, its exact mechanism in CRC remains unclear. Here, whole-transcriptome sequencing was employed to assess the long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) profiles of GA-Me-treated HCT116 cells. In total, 1572 differentially expressed (DE) lncRNAs, 123 DEcircRNAs, 87 DEmiRNAs, and 1508 DEmRNAs were identified. DCBLD2 and RAPGEF5 were validated as two core mRNAs in the DElncRNA, DEcircRNA, and DEmiRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological functions and potential mechanisms of TCONS-00008997, XR-925056.2, circRNA-07908, hsa-miR-100-3p, hsa-miR-1257, hsa-miR-3182, NAV3, ADAM20, and STARD4, which were altered after GA-Me treatment. The regulatory relationships of the XR-925056.2-hsa-miR-3182-NAV3/ADAM20/STARD4, circRNA-07908|Chr22:38986298-39025349-hsa-miR-3182-NAV3/ADAM20, ENST00000414039/ENST00000419190-novel874_mature-MMP9 and circRNA-00314|Chr1:35470863-35479212/circRNA-05460|Chr17:72592203-72649268-novel874_mature-MMP9 immune-regulatory networks involved both noncoding RNAs (ncRNAs) and mRNAs. Molecular docking studies showed that Zn2+ and the His201, His205, His211, Glu202, and Ala165 residues of MMP2 contributed to its high affinity for GA-Me. Zn2+ and the Glu402 and Gly186 residues of MMP9 are important for its interaction with GA-Me. Our results suggested and confirmed that GA-Me is a potential multitarget lead compound for CRC treatment with unique polypharmacological advantages.

The complete chloroplast genome of Strobilanthes crispus (Acanthaceae).

We reported and characterized the complete chloroplast genome sequence of Strobilanthes crispus Blume 1826. Strobilanthes crispus belongs to the Acanthaceae family and has a number of local names including Batuzin, Bayam Karang, Kotz Bellin, and Pekka Batu, which is native to Malaysian with diverse beneficial uses. Green leaves were determined using next-generation sequencing. We found that the entire chloroplast genome of S. crispus was 144,987 bp in length, included four segments, named a large single-copy (LSC) region (92,556 bp), a small single-copy (SSC) region (17,783 bp), and a pair inverted repeat regions (IRs) (17,324 bp in each), respectively. The chloroplast genome of S. crispus contained a total of 129 functional genes, including 84 protein-coding genes, 37 transfer RNAs (tRNAs), and eight ribosomal RNA (rRNA) genes. The phylogenetic tree reconstructed by nine chloroplast genomes reveals that S. crispus is most closely related to Strobilanthes bantonensis and Strobilanthes cusia.

The Relationship between Sleep Duration and Stroke Risk: The Mediating Role of Physical Activity.

Background: This study aimed to investigate the mediating effect of physical activity (PA) on the relationship between average sleep duration and risk of stroke in suburban residents without stroke. Methods: A cross-sectional study was executed, and participants were recruited through a multistage, stratified, probability-proportional-to-size sampling method in this research. The stroke risk was measured using a risk assessment form for a high-risk stroke population. The PA score was calculated by the Physical Activity Rating Scale-3 (PARS-3). The average sleep duration was calculated by adding up night sleep and afternoon nap durations. A multiple linear regression analysis was conducted to identify the association between stroke risk, average sleep duration, and PA. The direct and indirect effects of average sleep duration on stroke risk were analyzed by using the PA in a mediation framework. Results: A total of 5312 suburban residents (average: 54.96 ± 12.21 years, 2970 women) participated in the study. After adjusting for covariates, relatively inappropriate sleep duration (<7 h/>8 h~9 h/>9 h) and stroke risk were significantly associated, compared with the moderate average sleep duration (7~8 h) (ß = 0.038, 95% CI: 0.024~0.128; ß = 0.078, 95% CI: 0.128~0.250; ß = 0.150, 95% CI: 0.390~0.549). The PA total score (indirect effect ab = 0.013, 95% CI: 0.003~0.022) partially mediated the relationship between the long average sleep duration and stroke risk, in which the activity intensity (ab = −0.015, 95% CI: −0.021~−0.008), the activity duration (ab = 0.043, 95% CI: 0.029~0.058), and the activity frequency (ab = 0.012, 95% CI: 0.004~0.020; ab = 0.037, 95% CI: 0.026~0.050) all played a mediating role in the different sleep duration. Conclusions: A significant relationship between a long average sleep duration and stroke risk factors among people without stroke was found in this study. The PA and its components partially mediated the association between a long average sleep duration and stroke risk. Suitable prevention methods and interventions for PA and sleep may reduce the risk of stroke.

Nogo-B promotes angiogenesis and improves cardiac repair after myocardial infarction via activating Notch1 signaling.

Nogo-B (Reticulon 4B) is reportedly a regulator of angiogenesis during the development and progression of cancer. However, whether Nogo-B regulates angiogenesis and post-myocardial infarction (MI) cardiac repair remains elusive. In the present study, we aimed to explore the role and underlying mechanisms of Nogo-B in cardiac repair during MI. We observed an increased expression level of Nogo-B in the heart of mouse MI models, as well as in isolated cardiac microvascular endothelial cells (CMECs). Moreover, Nogo-B was significantly upregulated in CMECs exposed to oxygen-glucose deprivation (OGD). Nogo-B overexpression in the endothelium via cardiotropic adeno-associated virus serotype 9 (AAV9) with the mouse endothelial-specific promoter Tie2 improved heart function, reduced scar size, and increased angiogenesis. RNA-seq data indicated that Notch signaling is a deregulated pathway in isolated CMECs along the border zone of the infarct with Nogo-B overexpression. Mechanistically, Nogo-B activated Notch1 signaling and upregulated Hes1 in the MI hearts. Inhibition of Notch signaling using a specific siRNA and γ-secretase inhibitor abolished the promotive effects of Nogo-B overexpression on network formation and migration of isolated cardiac microvascular endothelial cells (CMECs). Furthermore, endothelial Notch1 heterozygous deletion inhibited Nogo-B-induced cardioprotection and angiogenesis in the MI model. Collectively, this study demonstrates that Nogo-B is a positive regulator of angiogenesis by activating the Notch signaling pathway, suggesting that Nogo-B is a novel molecular target for ischemic disease.

Effects of the Targeted Regulation of CCRK by miR-335-5p on the Proliferation and Tumorigenicity of Human Renal Carcinoma Cells.

Cell cycle-related kinase (CCRK) is most closely related to cyclin-dependent protein kinase, which may activate cyclin-dependent kinase 2 and is associated with the growth of human cancer cells. However, the expression and function of CCRK in the pathogenesis of clear cell renal cell cancer (ccRCC) are unclear. Herein, this research aimed to explore the potential mechanism of the targeted regulation of CCRK by miR-335-5p on the proliferation and tumorigenicity of human ccRCC cells. The results showed that CCRK was significantly overexpressed in ccRCC tissues and cells, and knockdown of the CCRK expression by shRNA inhibited cell proliferation in vitro and in vivo and enhanced cell apoptosis in vitro, which indicated that CCRK could be a potential target for antitumour drugs in the treatment of ccRCC. Moreover, miR-335-5p was found to bind directly to the 3' untranslated region of CCRK, was expressed at markedly low levels in ccRCC cells, and was closely associated with the tumour stage. The overexpression of CCRK partially reversed the inhibitory effects of miR-335-5p on the cell growth of ccRCC, which implied that miR-335-5p could serve as a promising tumour inhibitor for ccRCC. In summary, CCRK could serve as an alternative antitumour drug target, and miR-335-5p could be a promising therapeutic tumour inhibitor for ccRCC treatment.

Immunological and prognostic analysis of PSENEN in low-grade gliomas: An immune infiltration-related prognostic biomarker.

Metformin is widely used in the treatment of type 2 diabetes (T2D) and plays a role in antitumor and antiobesity processes. A recent study identified its direct molecular target, PEN2 (PSENEN). PSENEN is the minimal subunit of the multiprotein complex γ-secretase, which promotes the differentiation of oligodendrocyte progenitors into astrocytes in the central nervous system. This study was mainly based on gene expression data and clinical data from the TCGA and CGGA databases. Analysis of differential expression of PSENEN between tissues from 31 cancers and paracancerous tissues revealed that it had high expression levels in most cancers except 2 cancers. Using univariate Cox regression analysis and Kaplan-Meier survival analysis, a high expression level of PSENEN was shown to be a risk factor in low-grade gliomas (LGG). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that PSENEN is widely involved in immune-related signaling pathways in LGG. PSENEN expression level was significantly associated with TMB, MSI, tumor stemness index, and the expression levels of immunomodulatory genes in LGG. Finally, immune infiltration analysis revealed that PSENEN level was associated with the presence of various immune infiltrating cells, among which PSENEN was strongly associated with the presence of M2 macrophages and played a synergistic pro-cancer role. In conclusion, PSENEN may partially influence prognosis by modulating immune infiltration in patients with LGG, and PSENEN may be a candidate prognostic biomarker for determining prognosis associated with immune infiltration in LGG.

Corrigendum: Prognostic ferroptosis-related lncRNA signatures associated with immunotherapy and chemotherapy responses in patients with stomach cancer.

[This corrects the article DOI: 10.3389/fgene.2021.798612.].

The Long Noncoding RNA MEG3 Retains Epithelial-Mesenchymal Transition by Sponging miR-146b-5p to Regulate SLFN5 Expression in Breast Cancer Cells.

More and more studies have shown that long noncoding RNAs (lncRNAs) play essential roles in malignant tumors. The lncRNA MEG3 serves as a crucial molecule in breast cancer development, but the specific molecular mechanism needs to be further explored. We previously reported that Schlafen family member 5 (SLFN5) inhibits breast cancer malignant development by regulating epithelial-mesenchymal transition (EMT), invasion, and proliferation/apoptosis. Herein, we demonstrated that MEG3 was downregulated in pan-cancers and correlated with SLFN5 expression positively in breast cancer by bioinformatics analysis of TCGA and UCSC Xena data. Intervention with MEG3 positively affected SLFN5 expression in breast cancer cells. MEG3 repressed EMT and migration/invasion, similar to our previously reported functions of SLFN5 in breast cancer. Through bioinformatics analysis of starBase and LncBase data, 12 miRNAs were found to regulate both SLFN5 and MEG3, in which miR-146b-5p was confirmed to be regulated by MEG3 using MEG3 siRNA and overexpression method. MiR-146b-5p could bind to both SLFN5 3'UTR and MEG3, and inhibit their expression in a competing endogenous RNA mechanism, assayed by luciferase reporter and RNA pull down methods. Therefore, we conclude that MEG3 positively modulates SLFN5 expression by sponging miR-146b-5p and inhibits breast cancer development.

An Accessible Training Device for Children With Cerebral Palsy.

Walking and balance capabilities can be improved upon using repetitive ankle dorsiflexion exercises. Here we developed two types of pedal switches incorporated with training devices to improve their walking and balance performance of children with cerebral palsy. The first type of pedal switch can be used to operate a home appliance, while the second type of pedal switch can connect them to web games. Pedal switches can be used for home rehabilitation. This randomized controlled trial included patients in the intervention (n = 24) and control (n = 24) groups who completed 15 weeks of ankle training. The experimental group performed ankle dorsiflexion using a pressure-activated pedal switch connected to the web games. The control group performed ankle dorsiflexion exercises using a pedal switch that operated a home appliance (a fan). Standing balance and walking performance were estimated using the Zebris FDM system, a pressure force platform, the Pediatric Balance Scale score, and the 1-minute walk test. The pre- and posttest data were analyzed using analysis of variance and analysis of covariance, which revealed that the intervention group had more significant improvements in sway patterns and balance and walking. The developed facility of a modified pedal switch integrated with web games can achieve better exercise adherence to promote balance and walking performance than that with home appliances. Maintaining motivation in children with cerebral palsy plays a very important role in the rehabilitation process.

Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer.

Ferroptosis is associated with the prognosis and therapeutic responses of patients with various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed the combined effects of ferroptosis and lncRNAs on the prognosis and therapy of stomach cancer. In this study, transcriptomic and clinical data were downloaded from TCGA database, and ferroptosis-related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the Lasso algorithm, 10 prognostic ferroptosis-related lncRNAs (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) were screened to construct a prognostic model, which was verified in two test cohorts. Risk scores for patients with stomach cancer were calculated, and patients were divided into two risk groups. The low-risk group, based on the median value, had a longer overall survival time in the KM curve, and a lower proportion of dead patients in the survival distribution curve. Potential mechanisms and possible functions were revealed using GSEA and the ceRNA network. By integrating clinical information, the association between lncRNAs and clinical features was analyzed and several features affecting prognosis were identified. Then, a nomogram was developed to predict survival rates, and its good predictive performance was indicated by a relatively high C-index (0.67118161) and a good match in calibration curves. Next, the association between these lncRNAs and therapy was explored. Patients in the low-risk group had an immune-activating environment, higher immune scores, higher TMB, lower TIDE scores, and higher expression of immune checkpoints, suggesting they might receive a greater benefit from immune checkpoint inhibitor therapy. In addition, a significant difference in the sensitivity to mitomycin. C, cisplatin, and docetaxel, but not etoposide and paclitaxel, was observed. In summary, this model had guiding significance for prognosis and personalized therapy. It helped screen patients with stomach cancer who might benefit from immunotherapy and guided the selection of personalized chemotherapeutic drugs.

The Novel Regulatory Role of lncRNA-miRNA-mRNA Axis in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motor neurons, causing muscle atrophy, bulbar palsy, and pyramidal tract signs. However, the aetiology and pathogenesis of ALS have not been elucidated to date. In this study, a competitive endogenous RNA (ceRNA) network was constructed by analyzing the expression profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) that were matched by 7 ALS samples and 4 control samples, and then a protein-protein interaction (PPI) network was constructed to identify the genes related to ALS. Gene Ontology (GO) was used to study the potential functions of differentially expressed mRNAs (DEmRNAs) in the ceRNA network. For the ALS and control groups, 247177 potential lncRNA-mRNA ceRNA relationship pairs were screened. Analysis of significant relationship pairs demonstrated that the PPI modules formed by the MALAT1-regulated SYNRG, ITSN2, PICALM, AP3B1, and AAK1 genes may play important roles in the pathogenesis of ALS, and these results may help to characterize the pathogenesis of ALS.