Ferroptosis and its implications in treating cognitive impairment caused by aging: A study on the mechanism of repetitive transcranial magnetic stimulation.

OBJECTIVE: Ferroptosis has been recognized as being closely associated with cognitive impairment. Research has established that Alzheimer's disease (AD)-associated proteins, such as amyloid precursor protein (APP) and phosphorylated tau, are involved in brain iron metabolism. These proteins are found in high concentrations within senile plaques and neurofibrillary tangles. Repetitive transcranial magnetic stimulation (rTMS) offers a non-pharmacological approach to AD treatment. This study aims to explore the potential therapeutic effects of rTMS on cognitive impairment through the modulation of the ferroptosis pathway, thereby laying both a theoretical and experimental groundwork for the application of rTMS in treating Alzheimer's disease. METHODS: The study utilized senescence-accelerated mouse prone 8 (SAMP8) mice to model brain aging-related cognitive impairment, with senescence-accelerated-mouse resistant 1 (SAMR1) mice acting as controls. The SAMP8 mice were subjected to high-frequency rTMS at 25 Hz for durations of 14 and 28 days. Cognitive function was evaluated using behavioral tests. Resting-state functional magnetic resonance imaging (rs-fMRI) assessed alterations in cerebral activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygen level-dependent signal. Neuronal recovery post-rTMS in the SAMP8 model was examined via HE and Nissl staining. Immunohistochemistry was employed to detect the expression of APP and Phospho-Tau (Thr231). Oxidative stress markers were quantified using biochemical assay kits. ELISA methods were utilized to measure hippocampal levels of Fe2+ and Aß1-42. Finally, the expression of proteins related to the ferroptosis pathway was determined through western blot analysis. RESULTS: The findings indicate that 25 Hz rTMS enhances cognitive function and augments cerebral activity in SAMP8 model mice. Treatment with rTMS in these mice resulted in diminished oxidative stress and safeguarded neurons against damage. Additionally, iron accumulation was mitigated, and the expression of ferroptosis pathway proteins Gpx4, system Xc-, and Nrf2 was elevated. CONCLUSIONS: The Tau/APP-Fe-GPX4/system Xc-/Nrf2 pathway is implicated in the remedial effects of rTMS on cognitive dysfunction, offering a theoretical and experimental basis for employing rTMS in AD treatment.

Network Pharmacology and Molecular Docking Analysis on Mechanisms of Scutellariae Radix in the Treatment of Cerebral Ischemia-reperfusion Injury.

BACKGROUND: Multiple brain disorders are treated by Scutellaria Radix (SR), including cerebral ischemia-reperfusion (CI/R). However, more studies are needed to clarify the molecular mechanism of SR for CI/R. METHODS: The active substances and potential targets of SR and CI/R-related genes were obtained through public databases. Overlapping targets of SR and CI/R were analyzed using proteinprotein interaction (PPI) networks. GO and KEGG enrichment analyses were performed to predict the pathways of SR against CI/R, and the key components and targets were screened for molecular docking. The results of network pharmacology analysis were verified using in vitro experiments. RESULTS: 15 components and 64 overlapping targets related to SR and CI/R were obtained. The top targets were AKT1, IL-6, CAS3, TNF, and TP53. These targets have been studied by GO and KEGG to be connected to a number of signaling pathways, including MAPK, PI3K-Akt pathway, and apoptosis. Molecular docking and cell experiments helped to further substantiate the network pharmacology results. CONCLUSION: The active compound of SR was able to significantly decrease the apoptosis of HT22 cells induced by OGD/R. This finding suggests that SR is a potentially effective treatment for CI/R by modulating the MAPK and PI3K-Akt pathways.

Mid-infrared 1 W hollow-core fiber gas laser source.

We report the characteristics of a 1 W hollow-core fiber gas laser emitting CW in the mid-IR. Our system is based on an acetylene-filled hollow-core optical fiber guiding with low losses at both the pump and laser wavelengths and operating in the single-pass amplified spontaneous emission regime. Through systematic characterization of the pump absorption and output power dependence on gas pressure, fiber length, and pump intensity, we determine that the reduction of pump absorption at high pump flux and the degradation of gain performance at high gas pressure necessitate the use of increased gain fiber length for efficient lasing at higher powers. Low fiber attenuation is therefore key to efficient high-power laser operation. We demonstrate 1.1 W output power at a 3.1 µm wavelength by using a high-power erbium-doped fiber amplifier pump in a single-pass configuration, approximately 400 times higher CW output power than in the ring cavity previously reported.

[Effect of tobacco extracts on human gingival fibroblasts' proliferation and fibronectin expression].

PURPOSE: To investigate the influence and mechanism of smokeless tobacco (ST) extracts on proliferation and fibronectin expression of human gingival fibroblasts (HGFs) adhered to titanium plates. METHODS: The cultured primary HGFs with ST of different concentrations for a period of 2h and 2, 4, 6, 8 d was separately conducted; the cell proliferation and the adhesion was assayed using CCK-8 method; enzyme-linked immunosorbent assay was used to determine the content of supernatant fibronectin (FN) at different times. The data was analyzed with SPSS 19.0 software package. RESULTS: With the increase of ST concentration, the cell adherence rate decreased accordingly. With ST concentration of 5.0 g/L and 10 g/L, the adhesion rate was (34.316±7.725)% and (25.478±10.651)%, respectively, which was significantly lower than that of the control group (100%) (P<0.01). Cell proliferation on the titanium plate started at 2 d and 4 d and the cell abundance of the control group was significantly greater than that of ST group (P<0.05) with concentrations of 2.5, 5.0, 10 g/L; The cell abundance of the control group was significantly greater than that of ST group (P<0.05) with concentrations of 0.625-10 g/L on the 6th and 8th day. In 0.625, 1.25, 2.5 g/L ST group, FN concentration was (69.352±31.640), (23.595±8.625) and (7.292±2.865) ng/mL, respectively, which was significantly lower than that of the control group (142.188 ± 28.126) ng/mL (P<0.05). CONCLUSIONS: ST can significantly inhibit the proliferation and adhesion of HGFs on pure titanium surface, and the mechanism may be related to decrease of FN secreted by HGFs.

Experimental study of low-loss single-mode performance in anti-resonant hollow-core fibers.

Anti-resonant hollow-core fibers are optical fiber waveguides which exhibit very low dispersion, high damage threshold and ultra-low nonlinear response. However, they typically deliver the light in several spatial modes, whereas their application usually requires that they support a single spatial mode. We report the principles, fabrication, demonstration and characterization of anti-resonant hollow-core fibres with strong differential modal attenuations and low overall attenuations. These fibers perform as single-mode and are eminently suitable for delivery of powerful ultrashort optical pulses in machining, cutting, welding and multiphoton microscopy applications.

[Maxillary anterior tooth restoration by using fiber-reinforced composite with a natural tooth pontic: a case report].

Loss of anterior tooth impairs patients physically and emotionally as well as presents a challenge for dentists. This article presented a method of replacing one anterior tooth that was extracted because of periodontitis. The proposed method involves the use of the natural crown as pontic with fiber-reinforced composite resin-bonded fixed partial denture.