Spinal cord abnormal autophagy and mitochondria energy metabolism are modified by swim training in SOD1-G93A mice
AbstractAmyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared wi...
Source: Journal of Molecular Medicine - January 10, 2024 Category: Molecular Biology Source Type: research
Altered expression of Sialyl Lewis X in experimental models of Parkinson ’s disease
AbstractThe mechanisms underlying neurodegeneration in Parkinson ’s disease (PD) are still not fully understood. Glycosylation is an important post-translational modification that affects protein function, cell-cell contacts and inflammation and can be modified in pathologic conditions. Although the involvement of aberrant glycosylation has been proposed for PD , the knowledge of the diversity of glycans and their role in PD is still minimal. Sialyl Lewis X (sLeX) is a sialylated and fucosylated tetrasaccharide with essential roles in cell-to-cell recognition processes. Pathological conditions and pro-inflammatory mediat...
Source: Journal of Molecular Medicine - January 10, 2024 Category: Molecular Biology Source Type: research
PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy
AbstractLysosomes function as critical signaling hubs that govern essential enzyme complexes. LGALS proteins (LGALS3, LGALS8, and LGALS9) are integral to the endomembrane damage response. If ESCRT fails to rectify damage, LGALS-mediated ubiquitination occurs, recruiting autophagy receptors (CALCOCO2, TRIM16, and SQSTM1) and VCP/p97 complex containing UBXN6, PLAA, and YOD1, initiating selective autophagy. Lysosome replenishment through biogenesis is regulated by TFEB. LGALS3 interacts with TFRC and TRIM16, aiding ESCRT-mediated repair and autophagy-mediated removal of damaged lysosomes. LGALS8 inhibits MTOR and activates TF...
Source: Journal of Molecular Medicine - January 6, 2024 Category: Molecular Biology Source Type: research
Liquid –liquid phase separation in Alzheimer’s disease
AbstractThe pathological aggregation and misfolding of tau and amyloid- β play a key role in Alzheimer’s disease (AD). However, the underlying pathological mechanisms remain unclear. Emerging evidences indicate that liquid–liquid phase separation (LLPS) has great impacts on regulating human health and diseases, especially neurodegenerative diseases. A series of stu dies have revealed the significance of LLPS in AD. In this review, we summarize the latest progress of LLPS in AD, focusing on the impact of metal ions, small-molecule inhibitors, and proteinaceous partners on tau LLPS and aggregation, as well as toxic olig...
Source: Journal of Molecular Medicine - January 2, 2024 Category: Molecular Biology Source Type: research
The osteoporosis susceptibility SNP rs188303909 at 2q14.2 regulates EN1 expression by modulating DNA methylation and E2F6 binding
In this study, we identified rs188303909, a functional CpG-SNP, as a causal SNP for osteoporosis at 2q14.2 through the integration of functional and epigenomic analyses. Functional experiments demonstrated that unmethylated rs188303909 acted as a strong allele-specific distal enhancer to regulateEN1 expression by modifying the binding of transcription factor E2F6, but rs188303909 methylation attenuated the active effect of E2F6 onEN1 expression. Importantly, transcription factor EN1 could differentially bind osteoporosis GWAS lead SNPs rs4869739-T and rs4355801-G to upregulateCCDC170 andCOLEC10 expression, thus promoting b...
Source: Journal of Molecular Medicine - December 28, 2023 Category: Molecular Biology Source Type: research
Phosphorylation of RGS16 at Tyr168 promote HBeAg-mediated macrophage activation by ERK pathway to accelerate liver injury
AbstractLiver injury is closely associated with macrophage activation following HBV infection. Our previous study showed that only HBeAg, but not HBsAg and HBcAg, stably enhances inflammatory cytokine production in macrophages. And we also indicated that HBeAg could induce macrophage activation via TLR2 and thus aggravate the progression of liver fibrosis. However, the specific molecular mechanism of HBeAg in macrophage activation is not clear. We screened significantly overexpressed RGS16 from RNASeq results of HBeAg-stimulated macrophages and validated them with cellular assays, GSE83148 microarray dataset, and in clinic...
Source: Journal of Molecular Medicine - December 23, 2023 Category: Molecular Biology Source Type: research
A simple tool for evaluation of inflammation in psoriasis: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as markers in psoriasis patients and related murine models of psoriasis-like skin disease
This study evaluates neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in psoriasis patients and five murine models of psoriasis-like skin disease based on topical imiquimod application and overexpression of IL-17A under different promotors. We performed a single-center prospective observational study in a German population, investigating psoriasis patients prior to, 4 weeks, and 16 weeks post begin of systemic anti-inflammatory therapy. Psoriasis area and severity index (PASI), blood count, and C-reactive protein (CRP) levels were attained at each timepoint. Additionally, five murine models of...
Source: Journal of Molecular Medicine - December 21, 2023 Category: Molecular Biology Source Type: research
Correction to: Periostin secreted by cancer ‑associated fibroblasts promotes cancer progression and drug resistance in non‑small cell lung cancer
(Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - December 18, 2023 Category: Molecular Biology Source Type: research
Correction to: Efficient generation of gene-modified human natural killer cells via alpharetroviral vectors
(Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - December 7, 2023 Category: Molecular Biology Source Type: research
TAT-W61 peptide attenuates neuronal injury through blocking the binding of S100b to the V-domain of Rage during ischemic stroke
AbstractIschemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke thro...
Source: Journal of Molecular Medicine - December 5, 2023 Category: Molecular Biology Source Type: research
DSPE-PEG2000-methotrexate nanoparticles encapsulating phenobarbital sodium kill cancer cells by inducing pyroptosis
AbstractCancer is a life-threatening disease worldwide. Nanomedicine and nanodelivery systems are recently developed scientific field that employs specific materials in the nanoscale range to deliver drugs. Lipid-based nanoparticles are an ideal delivery system since they exhibit many advantages, including high bioavailability, self-assembly, formulation simplicity, and the ability to exhibit a plethora of physicochemical properties. Herein, we report that phenobarbital sodium can kill cancer cells by using the DSPE-PEG2000-methotrexate nanoparticle delivery system, which can target folate receptors that are usually overex...
Source: Journal of Molecular Medicine - December 4, 2023 Category: Molecular Biology Source Type: research
Effects of different amosite preparations on macrophages, lung damages, and autoimmunity
AbstractThe underlying mechanisms of asbestos-related autoimmunity are poorly understood. As the size, surface reactivity, and free radical activity of asbestos particles are considered crucial regarding the health effects, this study aims to compare the effects of exposure to pristine amosite (pAmo) or milled amosite (mAmo) particles on lung damage, autoimmunity, and macrophage phenotype. Four months after lung exposure to 0.1 mg of amosite, BAL levels of lactate dehydrogenase, protein, free DNA, CCL2, TGF-β1, TIMP-1, and immunoglobulin A of pAmo-exposed C57Bl/6 mice were increased when compared to fluids from control-...
Source: Journal of Molecular Medicine - November 28, 2023 Category: Molecular Biology Source Type: research
Sphingolipids: drivers of cardiac fibrosis and atrial fibrillation
AbstractSphingolipids (SLs) are vital constituents of the plasma membrane of animal cells and concurrently regulate numerous cellular processes. An escalating number of research have evinced that SLs assume a crucial part in the progression of tissue fibrosis, a condition for which no efficacious cure exists as of now. Cardiac fibrosis, and in particular, atrial fibrosis, is a key factor in the emergence of atrial fibrillation (AF). AF has become one of the most widespread cardiac arrhythmias globally, with its incidence continuing to mount, thereby propelling it to the status of a major public health concern. This review ...
Source: Journal of Molecular Medicine - November 28, 2023 Category: Molecular Biology Source Type: research
Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment
AbstractAs SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in S ão Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for unt...
Source: Journal of Molecular Medicine - November 27, 2023 Category: Molecular Biology Source Type: research
IL-23 contributes to Particulate Matter induced allergic asthma in the early life of mice and promotes asthma susceptibility
This study aimed to investigate changes in allergic phenotypes and effects on allergen-specific memory T cells resulting from co-exposure of mice in the early life to PM and house dust mites (HDM) and to explore the role of interleukin-23 (IL-23) in this process. PM and low-dose HDM were administered intranasally in 4-day-old C57BL/6 mice. After confirming an increase in IL-23 expression in mouse lung tissues, changes in the asthma phenotype and lung effector/memory Th2 or Th17 cells were evaluated after intranasal administration of anti-IL-23 antibody (Ab) during co-exposure to PM and HDM. Evaluation was performed up to 7...
Source: Journal of Molecular Medicine - November 23, 2023 Category: Molecular Biology Source Type: research
