Abstract Background Neuroinflammation mediated by microglia is an important pathological process of neurodegenerative diseases. Alleviating the inflammatory response caused by activated microglia might be a valuable treatment. The 18-kDa translocator protein (TSPO), as a marker of neuroinflammation, is significantly elevated in activated microglia. But the function of TSPO in microglia has not been well demonstrated. Methods In this study, we evaluated the role of TSPO and its ligands in LPS-activated BV-2 microglia involving mitophagy pathway and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Then, in the microglia-neuron co-culture system, the neurotoxicity induced by LPS-activated microglia and the neuroprotective effects of TSPO ligands were evaluated. Results Our results showed that after stimulated by LPS, TSPO expression was increased, meanwhile the expression of autophagy associated proteins were decreased in BV-2 microglia cells, but the reduction was reversed by pretreatment with PK11195 and Midazolam. Simultaneously, the NLRP3 inflammasome were increased in LPS activated BV-2 microglia in Transwell co-culture system, pretreatment with TSPO ligands could curb this undesirable situation. Furthermore, TSPO ligands improved the cell viability and reduced apoptosis of neuronal cells in co-culture system. Conclusions TSPO ligands PK11195 and Midazolam showed neuroprotective effects by reducing the inflammatory response of LPS-activated microglia, which may be related to the enhancement of mitophagy and the inhibition of NLRP3 inflammasome.
Objective The widespread use of nanoparticles in recent years has increased the risk of ocular exposure. zinc oxide (ZnO) is widely used in the field of cosmetics because of its unique chemical properties. The application of graphene oxide (GO) as an emerging nanomaterial in the field of eye drops is also gradually emerging. Currently, research on ZnO and GO eye exposure mainly focuses on application or toxicity to optic nerve cells. There's less study on corneal wound healing effects. and the previous research hasn't compared ZnO and GO corneal toxicity.
Abstract Aim: To assess whether non‐pharmacological and/or pharmacological measures lead to decreased pain during an eye examination in preterm infants. Methods: . Design: Systematic review. Subjects: Premature infants meeting the criteria for screening eye examination for retinopathy. Intervention: Databases were searched through the Ovid interface. Randomized and quasi‐randomized controlled trials were included. Data were assessed independently by three reviewers. Main outcome measures: Pain assessed by Premature Infant Pain Profile (PIPP) or physiological changes. Results: Eight studies were included and grouped according to intervention: oral sucrose (group 1), anaesthetic eye drops (group 2) and non‐pharmacological measures (group 3). For group 1, the mean PIPP score with sucrose was 1.38 (WMD) (95% CI: 0.41–2.35) lower than that of placebo (p = 0.005). For group 2, one study showed a reduction of two points on the PIPP score with topical proparacaine, whereas another showed no benefit. For group 3, developmental care improved developmental scores and salivary cortisol in one study. Conclusion: Sucrose reduced pain during the eye examination, whereas the efficacy of proparacaine was not consistent in the studies included. However, PIPP scores remained relatively high in all the studies; thus further research is required to delineate better pain reduction strategies.
Mechanical ventilation (MV) may lead to ventilator-induced lung injury (VILI). Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against VILI and to explore the possible molecular mechanisms using the rat model. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to 5 groups (n = 6): control, low tidal volume MV (LMV), high tidal volume (HVT) MV (HMV), HVT MV + dexmedetomidine (DEX), HVT MV + dexmedetomidine + yohimbine (DEX+Y). Rats were euthanized after being ventilated for 4 hours. Pathological changes, lung wet/dry (W/D) weight ratio, lung myeloperoxidase (MPO) activity, levels of inflammatory cytokines (i.e., interleukin [IL]-1β, tumor necrosis factor alpha [TNF-α], and IL-6) in the bronchoalveolar lavage fluid (BALF) and lung tissues, expression of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB, and activation of NF-κB in lung tissues were measured. Compared with HMV, DEX group showed fewer pathological changes, lower W/D ratios and decreased MPO activity of the lung tissues and lower concentrations of the inflammatory cytokines in the BALF and lung tissues. Dexmedetomidine significantly inhibited the expression of TLR4 and NF-κB and activation of NF-κB. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to HVT-MV and had a protective effect against VILI, with the inhibition of the TLR4/NF-κB signaling pathway, at least partly via α2-adrenoceptors.
Abstract Background Observational studies have found that dietary intake and certain micronutrients are associated with microvascular complications of diabetes. However, the exact causal relationship is unclear. Methods Causal associations of dietary intake and micronutrients with 2 diabetic microvascular complications (diabetic retinopathy and diabetic nephropathy) were explored using two-sample Mendelian randomization analyses, respectively. Genetic data related to dietary intake were obtained from the IEU public database, and genetic data related to micronutrients were obtained from previous genome-wide association studies. Summary statistics for microvascular complications of diabetes were obtained from the FinnGen consortium. Random-effects inverse variance weighted estimation was used as the primary method. Heterogeneity was tested using Cochran's Q statistic. The MR-Egger intercept was used to test for pleiotropy. In addition, we used leave-one-out analysis to test for the presence of SNPs that independently influenced the results. Results Inverse variance weighted estimates suggest coffee intake leads to increased risk of DR [OR = 2.15, 95%CI(1.44–3.20), p = 1.68E-04] and DN [OR = 3.34, 95%CI(1.72–6.46), p = 3.54E-04]. Cheese intake has a protective effect on DR [OR = 0.50, 95%CI(0.34–0.74), p = 4.39E-04]. No significant correlation was observed between micronutrients and two diabetic microvascular complications. Conclusions These findings expose a causal relationship between diet and microvascular complications of diabetes. Coffee intake was associated with an increased risk of DR and DN. Cheese intake was associated with decreased risk of DR.
Background: Microvascular bifurcation asymmetry is of significance for regulation of coronary flow heterogeneity during juvenile and adult growth. The aim of the study is to investigate the morphometric and hemodynamic variation of coronary arterial bifurcations in mice of different ages. Methods: Pulsatile blood flows were computed from a Womersley-type model in the reconstructed left coronary arterial (LCA) trees from Micro-CT images in normal mice at ages of 3 weeks, 6 weeks, 12 weeks, 5-6 months, and >8 months. Diameter and flow ratios and bifurcation angles were determined in each bifurcation of the LCA trees. Results: The blood volume and inlet flow rate of LCA trees increase and decrease during juvenile and adult growth, respectively. As vessel diameters decrease, the increased ratios of small to large daughter vessel diameters (D_s/D_m) result in more uniform flows and lower velocities. There are significant structure-functional changes of LCA trees in mice of >8 months compared with mice of <8 months. As D_s/D_m increases, the variation trend of bifurcation angle during juvenile growth is different from that during adult growth. Conclusions: Although inlet flows are different in adult vs juvenile mice, the adult still have uniform flow and low velocity. This is accomplished through a decrease in diameter. The design ensures ordered dispersion of red cells through asymmetric branching patterns into the capillaries.
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