Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats.

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.

Trace analysis of 47 psychotropic medications in environmental samples by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Psychotropic medications are one of the most prescribed pharmaceuticals in the world. Given their frequent detection and ecotoxicity to the no-target organism, the emission of these medications into environments has gradually draw attention. The study developed a sensitive and reliable analytic method to simultaneously investigate 47 psychotropic medications in four matrices: wastewater, surface water, activated sludge, and sediment by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). These 47 target analytes include 24 antidepressants, 17 antianxiety drugs, 5 anticonvulsants, and 1 relevant hormone. Solid phase extraction (SPE) was employed to extract analytes from water-phase samples. Ultrasonic Solvent Extraction method with Enhanced Matrix Removal clean-up (USE-EMR) was utilized to extract target compounds from solid-phase samples, which requires more straightforward and convenient procedures than previous methods. The extraction recoveries of all analytes ranged from 80 % to 120 % in these four sample matrices. In this study, The limit of quantitation for 47 psychotropic medications were 0.15 ng/L (estazolam) to 2.27 ng/L (lorazepam), 0.08 ng/L (desvenlafaxine) to 2 ng/L (mianserin), 0.22 ng/g (dry weight, dw) (nordiazepam) to 3.65 ng/g (dw) (lorazepam), and 0.07 ng/g (dw) (carbamazepine) to 2.85 ng/g (lorazepam), in wastewater, surface water, sludge, and sediment, respectively. In addition, the developed method was employed to analyse actual samples in two wastewater treatment plants and their receiving rivers. Carbamazepine, escitalopram, clozapine, desvenlafaxine, diazepam, lamotrigine, sertraline, temazepam, and venlafaxine were nearly ubiquitous in all matrices. Moreover, this study indicated that the inadequate removal efficiencies of psychotropic medications in wastewater treatment plants (WWTPs) had resulted in a persistent discharge of these contaminants from human sources into environments.

Electroacupuncture Alleviates Dry Eye Ocular Pain Through TNF-ɑ Mediated ERK1/2/P2X3R Signaling Pathway in SD Rats.

Purpose: This study aimed to examine electroacupuncture's influence on ocular pain and its potential modulation of the TNF-ɑ mediated ERK1/2/P2X3R signaling pathway in dry eye-induced rat models. Methods: Male Sprague-Dawley rats with induced dry eye, achieved through extraorbital lacrimal gland removal, were treated with electroacupuncture. Comprehensive metrics such as the corneal mechanical perception threshold, palpebral fissure height, eyeblink frequency, eye wiping duration, behavioral changes in the open field test, and the forced swimming test were employed. Additionally, morphological changes in microglia and neurons were observed. Expression patterns of key markers, TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R, in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) regions, were studied with etanercept serving as a control to decipher the biochemistry of electroacupuncture's therapeutic effects. Results: Electroacupuncture treatment demonstrated a notable decrease in the corneal mechanical perception threshold, improvement in palpebral fissure height, and significant reductions in both eyeblink frequency and eye wiping duration. Moreover, it exhibited a promising role in anxiety alleviation. Notably, the technique effectively diminished ocular pain by curbing microglial and neuronal activation in the TG and SpVc regions. Furthermore, it potently downregulated TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R expression within these regions. Conclusion: Electroacupuncture attenuated damage to sensory nerve pathways, reduced pain, and eased anxiety in dry eye-afflicted rats. The findings suggest a crucial role of TNF-ɑ mediated ERK1/2/P2X3R signaling pathway inhibition by electroacupuncture in these benefits.