Ruili Wang

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.

(1) Background: Many studies have shown that microgravity experienced by astronauts or long-term bedridden patients results in increased oxidative stress and bone loss. Low-molecular-weight chondroitin sulfates (LMWCSs) prepared from intact chondroitin sulfate (CS) have been demonstrated to possess good antioxidant and osteogenic activities in vitro. This study aimed to assess the antioxidant activity of the LMWCSs in vivo and evaluate their potential in preventing microgravity-induced bone loss. (2) Methods: we used hind limb suspension (HLS) mice to simulate microgravity in vivo. We investigated the effects of LMWCSs against oxidative stress damage and bone loss in HLS mice and compared the findings with those of CS and a non-treatment group. (3) Results: LMWCSs reduced the HLS-induced oxidative stress level, prevented HLS-induced alterations in bone microstructure and mechanical strength, and reversed changes in bone metabolism indicators in HLS mice. Additionally, LMWCSs downregulated the mRNA expression levels of antioxidant enzyme- and osteogenic-related genes in HLS mice. The results showed that overall effect of LMWCSs was better than that of CS. (4) Conclusions: LMWCSs protect against the bone loss caused by simulated microgravity, which may be related to their ability to reduce oxidative stress. LMWCSs can be envisaged as potential antioxidants and bone loss protective agents in microgravity.

Herein, an ultra-sensitive and facile electrochemical biosensor for procalcitonin (PCT) detection was developed based on NiCoP/g-C₃N₄ nanocomposites. Firstly, NiCoP/g-C₃N₄ nanocomposites were synthesized using hydrothermal methods and then functionalized on the electrode surface by π-π stacking. Afterward, the monoclonal antibody that can specifically capture the PCT was successfully linked onto the surface of the nanocomposites with a 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS) condensation reaction. Finally, the modified sensor was employed for the electrochemical analysis of PCT using differential Pulse Voltammetry(DPV). Notably, the larger surface area of g-C₃N₄ and the higher electron transfer capacity of NiCoP/g-C₃N₄ endow this sensor with a wider detection range (1 ag/mL to 10 ng/mL) and an ultra-low limit of detection (0.6 ag/mL, S/N = 3). In addition, this strategy was also successfully applied to the detection of PCT in the diluted human serum sample, demonstrating that the developed immunosensors have the potential for application in clinical testing.

MicroRNAs (miRNAs) are promising biomarkers for different pathological models because of their stable and detectable characters in biofluids. Here, we collected urine samples from 5 beagle dogs on the 3th, 6th, and 12th day in an acute kidney injury (AKI) caused by gentamycin. miRNA levels were measured with high-throughput sequencing and the results were then differentially investigated. Gene Ontology (GO) and KEGG pathway analysis were performed to analyze potential target genes corresponding to the differentially expressed miRNAs (DE-miRNAs). Relationships between hub genes and DE-miRNAs were analyzed with STRING and Cytoscape. We identified 234 DE-miRNAs 3, 6, and 12 days after gentamycin treatment (p < 0.05). Top 10 up- and down-regulated candidate target genes of DE-miRNAs were predicted by overlapping TargetScan and miRanda results). GO and KEGG analyses for DE-miRNAs demonstrated that the DE-miRNAs target genes are mainly involved in kidney injury-related pathways, such as the insulin signaling pathway, oxytocin signaling pathway, and hedgehog signaling pathway. The network of miRNA-hub genes suggests that miR-452, miR-106a, and 106b participate in regulating the largest number of hub genes. We evaluated the miRNA signature via a canine model built by gentamycin-caused acute kidney injury. Our results represent a valuable resource for evaluating miRNAs as biomarkers of renal toxicity.

Pefloxacin (PFLX) is a type of fluoroquinolone (FQ) that has been widely used in aquaculture and animal husbandry. It is also a new kind of pseudo-persistent pollutant, which has some toxic effects. In this study, zebrafish (Danio rerio) embryos were used as exposure models to analyze the toxicity of PFLX. The results showed that PFLX was absorbed on the outer membrane surface at the beginning, and then a few PFLX slowly entered the cytoplasm. The adsorption complied with the Langmuir isotherm adsorption model. The surface morphology of the embryonic membrane was changed. PFLX exposure had no effect on fetal autonomous movement, but it significantly inhibited the embryo hatching rate. After PFLX exposure, the embryo and larval survival rates showed a clear dose–effect relationship. Though PFLX exposure did not cause teratogenic toxicity, it still affected cardiovascular function. The potential toxicity mechanism and developmental toxicity of PFLX to zebrafish were revealed. These results could be important for studies concerning FQ toxicology.