Exploring the role of Prx II in mitigating endoplasmic reticulum stress and mitochondrial dysfunction in neurodegeneration.

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.

Identification and diagnostic potential of serum microRNAs as biomarkers for early detection of Alzheimer's disease.

This study aimed to investigate the differential expression of serum microRNAs in cognitive normal subjects (NC), patients with mild cognitive impairment (MCI), and patients with Alzheimer's disease (AD), with the objective of identifying potential diagnostic biomarkers. A total of 320 clinical samples, including 32 MCI patients, 288 AD patients, and 288 healthy controls, were collected following international standards. The expression of microRNAs in serum was analyzed using the Agilent human microRNA oligonucleotide microarray, and bioinformatics methods were employed to predict target genes and their involvement in AD-related pathways. Among the 122 microRNAs screened, five microRNAs (hsa-miR-208a-5p, hsa-miR-125b-1-3p, hsa-miR-3194-3p, hsa-miR-4652-5p, and hsa-miR-4419a) exhibited differential expression and met quality control standards. Bioinformatics analysis revealed that the target genes of these microRNAs were involved in multiple AD-related pathways, which changed with disease progression. These findings demonstrate significant differences in serum microRNA expression between NC, MCI, and AD patients. Three microRNAs were identified as potential candidates for the development of diagnostic models for MCI and AD. The results highlight the crucial role of microRNAs in the pathogenesis of AD and provide a foundation for the development of novel therapeutic strategies and personalized treatment approaches for AD. This study contributes to the understanding of AD at the molecular level and offers potential avenues for early diagnosis and intervention in AD patients.

A foot structure study of new arch flexibility grading system based on three-dimensional arch volume.

PURPOSE: Different arch structures may cause different foot function injuries. In the past, the arch structure and flexibility of the foot were often defined by the height of the arch, and there was no three-dimensional (3D) structure classification method. In order to form a more complete 3D description, we propose a new classification system of arch volume flexibility (AVF), and then use this new classification system to investigate the relationship between the AVF and arch index (AI), and the arch height flexibility (AHF) and AI, respectively. METHODS: It is proposed to recruit 180 young male adults for the test. We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement. Based on these data, we calculated the AHF and the AVF. Using the quintile method, these arches are divided into very stiff, stiff, neutral, flexible, and very flexible. According to AI value, all arches were divided into cavus, rectus, and planus. The distribution of AVF was compared using χ2 goodness of fit test. The spearman correlation test was used to compare the AHF and AVF. A p < 0.05 indicates that the difference is statistically significant. RESULTS: All participants' plantar data was obtained through 3D scanning, but only 159 of them were complete, so only 318 feet had valid data. The left AHF is (21.23 ± 12.91) mm/kN, and the right AHF is (21.71 ± 12.69) mm/kN. The AVF of the left foot arch is (207.35 ± 118.28) mm3/kg, while the right one is (203.00 ± 117.92) mm3/kg, and the total AVF of the arch was (205.17 ± 117.94) mm3/kg. There was no statistical difference in the AVF between the left and right feet for the same participant (n = 159, p = 0.654). In cavus, the percentage of arch with AVF is 21.4% (very stiff), 21.4% (stiff), 14.3% (neutral), 7.1% (flexible), and 35.7% (very flexible). In rectus, the percentage of arch with AVF is 23.9% (very stiff), 19.6% (stiff), 14.7% (neutral), 24.5% (flexible), and 17.2% (very flexible). In planus, the percentage of arch with AVF is 14.9% (very stiff), 20.6% (stiff), 27.0% (neutral), 16.3% (flexible), and 21.3% (very flexible). Moreover, the correlation between AHF and AVF is not significant (p = 0.060). CONCLUSION: In cavus, rectus, and planus, different AVF accounts different percentage, but the difference is not statistically significant. AVF is evenly distributed in the arches of the feet at different heights. We further found the relationship between AHF and AVF is not significant. As a 3D index, AVF may be able to describe the flexibility of the arch more comprehensively than AHF.

Regulatory pathway underpinning the development of encephalitis after simian immunodeficiency virus infection in rhesus macaques (Macaca mulatta).

BACKGROUND: Simian immunodeficiency virus (SIV) infection in rhesus macaques (Macaca mulatta) can lead to the development of SIV encephalitis (SIVE), which is closely related to human immunodeficiency virus (HIV)-induced dementia. METHODS: This was done by analyzing SIV and SIVE encephalitis in infected M. mulatta hippocampus samples from two microarray data sets, identifying two groups of common differentially expressed genes and predicting associated protein interactions. RESULTS: We found that eight genes-MX1, B2M, IFIT1, TYMP, STAT1, IFI44, ISG15, and IFI27-affected the negative regulation of biological processes, hepatitis C and Epstein-Barr viral infection, and the toll-like receptor signaling pathway, which mediate the development of encephalitis after SIV infection. In particular, STAT1 played a central role in the process by regulating biopathological changes during the development of SIVE. CONCLUSION: These findings provide a new theoretical basis for the treatment of encephalopathy after HIV infection by targeting STAT1.