Major depressive disorder (MDD) is a neuropsychiatric disorder, which remains challenging to diagnose and manage due to its complex endophenotype. In this aspect, circulatory microRNAs (cimiRNAs) offer great potential as biomarkers and may provide new insights for MDD diagnosis. Therefore, we systemically reviewed the literature to explore various cimiRNAs contributing to MDD diagnosis and underlying molecular pathways. A comprehensive literature survey was conducted, employing four databases from 2012 to January 2021. Out of 1004 records, 157 reports were accessed for eligibility criteria, and 32 reports meeting our inclusion criteria were considered for in-silico analysis. This study identified 99 dysregulated cimiRNAs in MDD patients, out of which 20 cimiRNAs found in multiple reports were selected for in-silico analysis. KEGG pathway analysis indicated activation of ALS, MAPK, p53, and P13K-Akt signaling pathways, while gene ontology analysis demonstrated that most protein targets were associated with transcription. In addition, chromosomal location analysis showed clustering of dysregulated cimiRNAs at proximity 3p22-p21, 9q22.32, and 17q11.2, proposing their coregulation with specific transcription factors primarily involved in MDD physiology. Further analysis of transcription factor sites revealed the existence of HIF-1, REST, and TAL1 in most cimiRNAs. These transcription factors are proposed to target genes linked with MDD, hypothesizing that first-wave cimiRNA dysregulation may trigger the second wave of transcription-wide changes, altering the protein expressions of MDD-affected cells. Overall, this systematic review presented a list of dysregulated cimiRNAs in MDD, notably miR-24-3p, let 7a-5p, miR-26a-5p, miR135a, miR-425-3p, miR-132, miR-124 and miR-16-5p as the most prominent cimiRNAs. However, various constraints did not permit us to make firm conclusions on the clinical significance of these cimiRNAs, suggesting the need for more research on single blood compartment to identify the biomarker potential of consistently dysregulated cimiRNAs in MDD, as well as the therapeutic implications of these in-silico insights.

Depression is a psychiatric disorder that presents with a persistent depressed mood as the main clinical feature and is accompanied by cognitive impairment. Changes in neuroplasticity and neurogenesis greatly affect depression. Without genetic changes, epigenetic mechanisms have been shown to function by regulating gene expression during the body’s adaptation to stress. Studies in recent years have shown that as important regulatory factors in epigenetic mechanisms, microRNAs (miRNAs) play important roles in the development and progression of depression through the regulation of protein expression. Herein, we review the mechanisms of miRNA-mediated neuroplasticity in depression and discus synaptic structural plasticity, synaptic functional plasticity, and neurogenesis. Furthermore, we found that miRNAs regulate neuroplasticity through several signalling pathways to affect cognitive functions. However, these pathways do not work independently. Therefore, we try to identify synergistic correlations between miRNAs and multiple signalling pathways to broaden the potential pathogenesis of depression. In addition, in the future, dual-function miRNAs (protection/injury) are promising candidate biomarkers for the diagnosis of depression, and their regulated genes can potentially be used as target genes for the treatment of depression.

Neuritic plaques are one of the major pathological hallmarks of Alzheimer’s disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β- and γ-secretase. BACE1 is the main β-secretase in the pathogenic process of Alzheimer’s disease, which is believed to be a rate-limiting step of Aβ production. Presenilin 1 (PS1) is the active center of the γ-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene (PSEN1) are the most common cause of early onset familial Alzheimer’s disease (FAD). The PSEN1 mutations can alter the activity of γ-secretase on the cleavage of APP. Previous studies have shown that PSEN1 mutations increase the expression and activity of BACE1 and that BACE1 expression and activity are elevated in the brains of PSEN1 mutant knock-in mice, compared with wild-type mice, as well as in the cerebral cortex of FAD patients carrying PSEN1 mutations, compared with sporadic AD patients and controls. Here, we used a Psen1 knockout cell line and a PS1 inhibitor to show that PS1 affects the expression of BACE1 in vitro. Furthermore, we used sucrose gradient fractionation combined with western blotting to analyze the distribution of BACE1, combined with a time-lapse technique to show that PS1 upregulates the distribution and trafficking of BACE1 in the endoplasmic reticulum, Golgi, and endosomes. More importantly, we found that the PSEN1 mutant S170F increases the distribution of BACE1 in the endoplasmic reticulum and changes the ratio of mature BACE1 in the trans-Golgi network. The effect of PSEN1 mutations on BACE1 may contribute to determining the phenotype of early onset FAD.

So far, more than 25,000 brain diseases have been shown to be related to oxidative stress. Excessive free radicals and reactive oxygen species (ROS) can attack cells resulting in dysfunctional proteins, lipids, and nucleic acid, finally leading to imbalance of energy metabolism, cell death, gene mutation, and immune reaction. Therefore oxidative stress plays an important role in neuronal diseases. As a traditional Chinese medicine, Zhengtian Pill (ZTP) was reported to have the ability to reduce the blood viscosity of migraine model rats, with increased beta-endorphin, serotonin, adrenaline, and dopamine in brain tissue. Moreover ZTP can effectively accelerate blood circulation and attenuate blood coagulation. However, the molecular mechanisms of ZPT are still unclear. Through the behavioral test we found that ZTP can significantly improve depression-like behavior induced by LPS when rat was treated with ZTP (L 0.17 g/kg, M 0.34 g/kg, and H 0.7 g/kg) intraperitoneal injection once a day for 30 consecutive days. And ZTP can resist oxidative stress (>72 h) for a longer time. And ZTP can promote the levels of ATP and SOD and reduce the levels of ROS and MDA in the brain. At the same time, ZTP can have antioxidant stress through increasing the expression level of Nrf2/HO-1/P38. These results show that ZTP may be a potential antioxidant stress drug for variety of diseases associated with oxidative stress injury.

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is an energetic and persistent explosive with long-lasting properties. Rhodococcus sp. strain DN22 has been discovered to be a microbe capable of degrading RDX. Herein, the complete genome of Rhodococcus sp. strain DN22 was sequenced and analyzed. The entire sequences of genes that encoded the two proteins participating in RDX degradation in Rhodococcus sp. strain DN22 were obtained, and were validated through proteomic data. In addition, few studies have investigated the physiological changes and metabolic pathways occurring within Rhodococcus sp. cells when treated with RDX, particularly through mass spectrometry-based omics. Hence, proteomic and metabolomic analyses were carried out on Rhodococcus sp. strain DN22 with the existence or lack of RDX in the medium. A total of 3186 proteins were identified between the two groups, with 115 proteins being significantly differentially expressed proteins. There were 1056 metabolites identified in total, among which 130 metabolites were significantly different. Through the combined analysis of differential proteomics and metabolomics, KEGG pathways including two-component system, ABC transporters, alanine, aspartate and glutamate metabolism, arginine biosynthesis, purine metabolism, nitrogen metabolism, and phosphotransferase system (PTS), were observed to be significantly enriched. These findings provided ponderable perspectives on the physiological alterations and metabolic pathways in Rhodococcus sp. strain DN22, responding to the existence or lack of RDX. This study is anticipated to expand the knowledge of Rhodococcus sp. strain DN22, as well as advancing understanding of microbial degradation.

Excessive hydrogen peroxide causes oxidative stress in cells. The oxidation of two tyrosine residues in proteins can generate o,o′-dityrosine, a putative biomarker for protein oxidation, which plays critical roles in a variety of organisms. Thus far, few studies have investigated dityrosine crosslinking under endogenous or exogenous oxidative conditions at the proteome level, and its physiological function remains largely unknown. In this study, to investigate qualitative and quantitative dityrosine crosslinking, two mutant Escherichia coli strains and one mutant strain supplemented with H₂O₂ were used as models for endogenous and exogenous oxidative stress, respectively. By integrating high-resolution liquid chromatography—mass spectrometry and bioinformatic analysis, we created the largest dityrosine crosslinking dataset in E. coli to date, identifying 71 dityrosine crosslinks and 410 dityrosine loop links on 352 proteins. The dityrosine-linked proteins are mainly involved in taurine and hypotaurine metabolism, citrate cycle, glyoxylate, dicarboxylate metabolism, carbon metabolism, etc., suggesting that dityrosine crosslinking may play a critical role in regulating the metabolic pathways in response to oxidative stress. In conclusion, we have reported the most comprehensive dityrosine crosslinking in E. coli for the first time, which is of great significance in revealing its function in oxidative stress.