These results suggest that altered expression of hsa_circRNA_103636 in PBMCs is a potential novel biomarker for the diagnosis and treatment of MDD.
BackgroundThe criteria for diagnosing depression are based on behavioral observation and self-reporting of symptoms by the patients or guardians without any biological validation of the disease. This study aimed to identify long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) as robust and predictive biomarkers for diagnosis and therapy response in major depressive disorder (MDD).Material/MethodsWe used human lncRNA 3.0 microarray profiling (which covers 30,586 human lncRNAs), using PBMCs from five MDD patients and five controls. Differentially expressed lncRNAs in the PBMCs of MDD patients were identified, of which 10 candidate lncRNAs were selected for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 138 MDD patients and 63 healthy controls. Then among the 138 MDD patients who received standard antidepressant treatment, 30 were randomly selected for lncRNAs expression retesting and symptomatology assessments after three-weeks and six-weeks of antidepressant treatment.ResultsSix lncRNAs (TCONS_00019174, ENST00000566208, NONHSAG045500, ENST00000517573, NONHSAT034045, and NONHSAT142707) were significantly downregulated in MDD patients compared to control patients, and the area under the receiver operator curve (ROC) of these six lncRNAs cases, combined, was 0.719 (95% confidence interval (CI): 0.617–0.821). There was no difference in the expression of these six lncRNAs based on gender (p>0.05) or age (p>0.05).ConclusionsThese results suggest that the combined expression of six lncRNAs in PBMCs may serve as a potential biomarker for diagnosis and therapy response of MDD in the clinical setting.
Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5β1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.
Background WHO stated that nearly one million people commit suicide every year worldly, and 40% of the suicide completer suffered from depression. The primary aim of this study was to explore the association between long noncoding RNAs (lncRNAs) expression in peripheral blood mononuclear cells (PBMCs) and suicide risk of patients with major depressive disorder (MDD).MethodsUsing Human LncRNA 3.0 microarray profiling which includes 30,586 human lncRNAs and RT‐PCR, six down‐regulated lncRNAs were identified differentially expressed in MDD patients. According to suicidal ideation and suicidal attempt, the suicide risk of MDD patients was classified into suicidal ideation versus no suicidal ideation groups, and past attempt versus no past attempt groups, respectively. The expression of six lncRNAs in MDD patients and controls were examined by RT‐PCR.ResultsThe expression of six lncRNAs had significant differences between no suicidal ideation, suicidal ideation, and controls; corresponding lncRNAs associated with suicidal attempt had remarkable differences between no past attempt, past attempt, and controls. Additionally, only the expression of lncRNAs in suicidal ideation group and past attempt group markedly declined compared with controls.ConclusionsThis study indicated that the expression of six down‐regulated lncRNAs had a negative association with suicide risk in MDD patients, and the expression of lncRNAs in PBMCs could have the potential to help clinician judge the suicide risk of MDD patients to provide timely treatment and prevent suicide.
BackgroundDysfunction of long non-coding RNAs (lncRNAs) has been demonstrated to be involved in psychiatric diseases. However, the expression patterns and functions of the regulatory lncRNAs in schizophrenia (SZ) patients have rarely been systematically reported.Material/MethodsThe lncRNAs in peripheral blood mononuclear cells (PBMCs) were screened and compared between the SZ patients and demographically-matched healthy controls using microarray analysis, and then were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) method. Three verified significantly dysregulated lncRNAs of PBMCs were selected and then measured in SZ patients before and after the antipsychotic treatment. SZ symptomatology improvement was measured by Positive And Negative Syndrome Scale (PANSS) scores.ResultsOne hundred and twenty-five lncRNAs were significantly differentially expressed in SZ patients compared with healthy controls, of which 62 were up-regulated and 63 were down-regulated. Concurrent with the significant decrease of the PANSS scores of patients after the treatment, the PBMC levels of lncRNA NONHSAT089447 and NONHSAT041499 were strikingly decreased (P<0.05). Down-regulation of PBMC expression of NONHSAT041499 was significantly correlated to the improvement of positive and activity symptoms of patients (r=−0.444 and −0.423, respectively, P<0.05, accounting for 16.9% and 15.1%, respectively), and was also significantly associated with better outcomes (odds ratio 2.325 for positive symptom and 12.340 for activity symptom).ConclusionsLncRNA NONHSAT089447 and NONHSAT041499 might be involved in the pathogenesis and development of SZ, and the PBMC level of NONHSAT041499 is significantly associated with the treatment outcomes of SZ.
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