The Contribution of Non-Neuronal Cells in Neurodegeneration: From Molecular Pathogenesis to Therapeutic Challenges

Neuron loss occurring in neurodegenerative diseases represents just the final step in a series of events involving several cell types, other than neurons, that actively contribute to the overall pathogenic mechanisms by establishing harmful non-cell autonomous effects [...]

Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation

Identification of host factors involved in viral replication is an important approach in discovering viral pathogenic mechanisms and identifying potential therapeutic targets. Previously, we screened host proteins that were upregulated by EV71 infection.

Meta-analysis integrated with multi-omics data analysis to elucidate pathogenic mechanisms of age-related knee osteoarthritis in mice

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically-presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the two models. At the nexus of the three aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA.

miR-590-3 and SP1 Promote Neuronal Apoptosis in Patients with Alzheimer’s Disease via AMPK Signaling Pathway

Alzheimer’s disease (AD) is a progressive neurological degenerative illness with a hidden onset. Its pathogenesis is complicated, although with molecular biology research on cancer and targeted research on pathogenic mechanisms, good progress has not yet been made. Therefore, this work built a multifactor-driven neuronal apoptosis dysfunction module for the purpose of probing its underlying pathogenic mechanisms. We performed differential expression analysis, coexpression analysis, enrichment analysis, and hypergeometric tests to calculate the underlying regulatory effects of multifactors on the modules by the way of the whole gene expression profile of AD and identify a series of ncRNA (miR-320a) and TF (NFKB1). Additionally, we screened 10 modules corresponding to the Hub gene, which tend to regulate the physiological progress of inflammation, regulation of autophagy, cerebral cortex neuron differentiation, glial cell apoptotic, and so on. Meanwhile, Alzheimer’s disease is triggered by signaling pathways such as the MPK signaling pathway. In this study, a dysfunction module is utilized to verify that miR-590-3 and SP1 motility factors can regulate neurons in Alzheimer’s disease through the MPK signaling pathway, not only providing new insights into the pathogenesis of Alzheimer’s disease but also laying a solid theoretical foundation for the biologists to further cure Alzheimer’s disease.

Essential Thrombocythemia Following Immune thrombocytopenia With JAK2 V617F Mutation: A Case Report

Immune Thrombocytopenia (ITP) is an autoimmune bleeding disorder. Tyrosine Kinase JAK2 (JAK2 V617F) mutation occurs in nearly 60% of Essential Thrombocythemia (ET) patients. Both diseases produce impaired platelet. We describe a case with ET following ITP. So far, only 3 reports described ET following ITP. We report the fourth patient with JAK2 V617F mutation at the onset of ITP presented 20 years ago that needed splenectomy. The association of these two diseases may recommend similar pathogenic mechanisms between Myeloproliferative Neoplasms (MPNs) and ITP that should be further explored.

Maternal–Fetal Outcomes in Women with Endometriosis and Shared Pathogenic Mechanisms

The connection between endometriosis and pregnancy outcomes is trending among the research topics. Until recently, endometriosis and its painful symptomatology were considered to be alleviated by pregnancy. However, these beliefs have shifted, as emerging literature has demonstrated the role of this condition in affecting pregnancy evolution. The underlying pathogenesis of endometriosis is still poorly understood, all the more when pregnancy complications are involved. Debatable opinions on endometriosis associated with obstetric complications exist because of the potential bias resulting from the heterogeneity of preceding evidence. This review aims to evaluate the connection between endometriosis and adverse pregnancy outcomes and their shared pathogenic mechanisms. We searched PubMed and EMBASE and focused on the studies that include placenta praevia, premature rupture of membranes, spontaneous preterm birth, gestational hypertension, preeclampsia, obstetric hemorrhages (ante- and postpartum bleeding, abruptio placentae), miscarriage, stillbirth, neonatal death, gestational diabetes mellitus, gestational cholestasis, small for gestational age, and their association with endometriosis. Not only the risks of emergence were highlighted, but also the pathogenic connections. Epigenetic alterations of some genes were found to be mirrored both in endometriosis and obstetric complications. This review issues a warning for providing increased attention to pregnant women with endometriosis and newborns as higher risks of preeclampsia, placental issues, and preterm deliveries are associated.