Unusual neurological manifestations of bilateral medial medullary infarction: A case report

Bilateral medial medullary infarction (BMMI) is an extremely rare type of cerebrovascular accident often resulting in poor functional consequences. “Heart appearance” on diffusion-weighted imaging (DWI) of magnetic resonance imaging (MRI) is the unique presentation of BMMI. In this article, we present an acute ischemic stroke patient whose brain MRI showed the atypical “heart appearance” sign, manifested unusual bilateral central facial paralysis concurrently. For an early diagnosis of BMMI, it is essential to recognize the characteristic clinical and MRI findings of this rare type of stroke. Abnormal small dot or linear DWI signal at the midline of the brainstem should not be ignored at the early stage of stroke.

Gene signature to predict prognostic survival of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA–long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator’s feature selection detected four characteristic genes (SAPCD2, DKC1, CHRNA5, and UROD), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets (p <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.

The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma

Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein–protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.

Is there any effect on imprinted genes H19, PEG3, and SNRPN during AOA?

Assisted oocyte activation (AOA) has been proposed as an effective technique to overcome the problem of impaired fertilization after intracytoplasmic sperm injection (ICSI) but the safety of AOA remains a concern. We aimed to investigate if AOA induces imprinting effects on embryos. We used 13 cleavage embryos, nine blastocysts, and eight placentas from 15 patients. The subjects were divided into six groups by tissue type and with or without AOA. The methylation levels of imprinted genes (H19, paternally expressed gene [PEG3] and small nuclear ribonucleoprotein polypeptide N [SNRPN]) were tested by pyrosequencing. We observed different methylation levels among cleavage embryos. The variability was much more remarkable between cleavage embryos than blastocysts and placenta tissues. The methylation levels were especially higher in SNRPN and lower in the H19 gene in AOA embryos than those without AOA. No significant difference was found either among blastocysts or among placenta tissues regardless of AOA. The methylation levels of the three genes in blastocysts were very similar to those in the placenta. Compared to conventional ICSI, AOA changed imprinting methylation rates at H19 and SNRPN in cleavage embryos but not in the blastocyst stage and placenta. We recommend that blastocyst transfer should be considered for patients undergoing AOA during in vitro fertilization.

Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12

Background/aims Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology. Methods In this study, we assessed the expression level of microRNA-199a-5p (miR-199a-5p) in human ULM by quantitative polymerase chain reaction. After that cell counting kit 8, colony formation, 5-ethynyl-20-deoxyuridine, flow cytometry, and Western blot analyses were performed to investigate the effects of miR-199a-5p on ULM cell proliferation and apoptosis. Results We confirmed that miR-199a-5p was significantly downregulated in human ULM. The results of function analyses showed that miR-199a-5p inhibited cell proliferation and induced cell apoptosis in vitro. Bioinformatics tool showed oncogene MED12 was one of the target genes of miR-199a-5p, which mediated the effect of miR-199a-5p on the ULM. Conclusion Our results showed that miR-199a-5p functioned as an antitumor factor in human ULM cells. These findings broaden the current findings on the function of miR-199a-5p into the ULM pathogenesis, and miR-199a-5p may serve as a prognosis and therapeutic target for the ULM and its related diseases.

Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?

Background A large variety of factors can affect colorectal cancer (CRC) survival, including type 2 diabetes mellitus (T2DM) and paraneoplastic thrombocytosis. Although several common factors play a role in their development and platelets are damaged in both diseases, the combined relationship of the three conditions was never investigated previously. Methods A prospective, real-life observational cohort study was conducted with the inclusion of 108 CRC patients and 166 voluntary non-CRC subjects. Plasma interleukin-6 and thrombopoietin levels were measured. Results Study participants were divided into cohorts based on the presence of T2DM. Platelet count (p < 0.0500) and interleukin-6 (p < 0.0100) level were significantly higher in the CRC groups. Thrombopoietin level was higher in the T2DM, CRC, and CRC + T2DM groups (p < 0.0500). Analysis of parameter changes over time and survival models revealed that neither platelet count, interleukin-6, nor thrombopoietin levels were affected by T2DM. Death of patients was associated with higher baseline platelet count (p = 0.0042) and interleukin-6 level (p < 0.0001). Conclusion Although the independent, disease-worsening effect of paraneoplastic thrombocytosis and T2DM is known, the coexistence of the two did not further impair the survival of CRC patients, suggesting that T2DM has no significant effect over paraneoplastic thrombocytosis.

Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?

Background Chronic urticaria is a common disease. Plasmapheresis is an alternative treatment that can be appropriate for patients who are resistant to treatment with 2nd generation antihistamines or for whom treatment with omalizumab is unsuitable. Objective To investigate the effect of plasmapheresis treatment in chronic urticaria. Methods A retrospective analysis was performed based on the data of 98 patients suffering from refractory chronic urticaria who received plasmapheresis as an alternative treatment in Vilnius University’s Hospital Santaros Clinics from 2000 to 2020. The efficiency of the treatment was evaluated by clinical judgment. Results 58.2% of the patients exhibited a complete or significant response; of these, 37.8% had temporary relief of symptoms and 20.4% achieved disease remission; 41.8% showed no response to the plasmapheresis. Men (34.8%) had a tendency to achieve disease remission more often than women (16%) (p < 0.05). One patient did not finish the plasmapheresis treatment due to the symptoms’ exacerbation and treatment with omalizumab was initiated. Conclusion Plasmapheresis is a safe and effective alternative treatment when traditional treatment is unavailable or does not relieve symptoms completely. Our data showed that plasmapheresis was effective in more than half of our patients.

Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer associated with an unstable prognosis. Thus, there is an urgent demand for the identification of novel diagnostic and prognostic biomarkers as well as targeted drugs for LUAD. The present study aimed to identify potential new biomarkers associated with the pathogenesis and prognosis of LUAD. Three microarray datasets (GSE10072, GSE31210, and GSE40791) from the Gene Expression Omnibus database were integrated to identify the differentially expressed genes (DEGs) in normal and LUAD samples using the limma package. Bioinformatics tools were used to perform functional and signaling pathway enrichment analyses for the DEGs. The expression and prognostic values of the hub genes were further evaluated by Gene Expression Profiling Interactive Analysis and real-time quantitative polymerase chain reaction. Furthermore, we mined the “Connectivity Map” (CMap) to explore candidate small molecules that can reverse the tumoral of LUAD based on the DEGs. A total of 505 DEGs were identified, which included 337 downregulated and 168 upregulated genes. The PPI network was established with 1,860 interactions and 373 nodes. The most significant pathway and functional enrichment associated with the genes were cell adhesion and extracellular matrix-receptor interaction, respectively. Seven DEGs with high connectivity degrees (ZWINT, RRM2, NDC80, KIF4A, CEP55, CENPU, and CENPF) that were significantly associated with worse survival were chosen as hub genes. Lastly, top 20 most important small molecules which reverses the LUAD gene expressions were identified. The findings contribute to revealing the molecular mechanisms of the initiation and progression of LUAD and provide new insights for integrating multiple biomarkers in clinical practice.

Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4

Long noncoding RNA (lncRNA), specifically the upregulation of lncRNA NR2F1 antisense RNA 1 (NR2F1-AS1), has been involved in the progression of non-small cell lung cancer (NSCLC), but the mechanisms that underlie this remain unclear. In this study, the expression of NR2F1-AS1, miR-363-3p, and SOX4 was assessed in NSCLC cells. A loss-of-function assay was used to measure the tumorigenicity of NSCLC cells. The glycolysis and glutamine metabolism of NSCLC cells was also measured via extracellular acidification rate, consumption of glucose and glutamine, and production of lactate and ATP. The relationships among NR2F1-AS1, miR-363-3p, and SOX4 were detected via dual-luciferase reporter assay. HK-2, GLS1, and SOX4 levels were also analyzed. We found that both NSCLC tissues and cells had higher levels of NR2F1-AS1. Silencing of NR2F1-AS1 inhibited the tumorigenicity of cells in vitro and reduced the glycolysis and glutamine metabolism of NSCLC cells. Regarding its mechanism, NR2F1-AS1 positively regulated the SOX4 level by sponging miR-363-3p. Furthermore, miR-363-3p inhibition or SOX4 overexpression reversed the repressing role of sh-NR2F1-AS1 in the tumorigenicity of NSCLC cells. In summary, NR2F1-AS1 promotes the tumorigenicity of NSCLC cells by regulating miR-363-3p/SOX4.

Hearing loss and brain disorders: A review of multiple pathologies

Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer’s disease/dementia, Parkinson’s disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.