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"Guo, Tong"
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Enhancing fractalkine/CX3CR1 signalling pathway can reduce neuroinflammation by attenuating microglia activation in experimental diabetic retinopathy
The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin‐induced diabetic rats, glyoxal‐treated R28 cells and hypoxia‐treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba‐1, TSPO, NF‐κB, Nrf2 and inflammation‐related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal‐treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia‐treated microglia, which was largely dampened by FKN. The NF‐κB and Nrf2 expressions and intracellular ROS were up‐regulated in hypoxia‐treated microglia compared with that in normoxia control, and FKN significantly inhibited NF‐κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF‐κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation‐related cytokines and ROS, and protect the retina from diabetes insult.
Journal Article
الفنون والحرف الصينية /
يتناول كتاب (الفنون والحرف الصينية) والذي قام بتأليفه (هانغ جيان، قوه تشيو هوي) في حوالي (163) صفحة من القطع المتوسط موضوع (الزخرفة الصينة) مستعرضا المحتويات التالية : التاريخ والخلفية للفنون والحرف الصينية التقليدية-الفنون والحرف في مجال الأواني-الفنون والحرف في مجال الملابس-الفنون والحرف في مجال المفروشات-الفنون والحرف في مجال الزخرفة-الفنون والحرف في مجال التسلية-الفنون والحرف في مجال التجارة.
Book
Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration
Background
Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial–mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD.
Methods
In vivo, the induction of subretinal fibrosis was performed in male C57BL/6J mice through laser photocoagulation. Either FH535 (a β-catenin inhibitor) or Box5 (a Wnt5a inhibitor) was intravitreally administered on the same day or 14 days following laser induction. The RPE-Bruch's membrane-choriocapillaris complex (RBCC) tissues were collected and subjected to Western blot analysis and immunofluorescence to examine fibrovascular and Wnt-related markers. In vitro, transforming growth factor beta 1 (TGFβ1)-treated ARPE-19 cells were co-incubated with or without FH535, Foxy-5 (a Wnt5a-mimicking peptide), Box5, or Wnt5a shRNA, respectively. The changes in EMT- and Wnt-related signaling molecules, as well as cell functions were assessed using qRT-PCR, nuclear-cytoplasmic fractionation assay, Western blot, immunofluorescence, scratch assay or transwell migration assay. The cell viability of ARPE-19 cells was determined using Cell Counting Kit (CCK)-8.
Results
The in vivo analysis demonstrated Wnt5a/ROR1, but not Wnt3a, was upregulated in the RBCCs of the laser-induced CNV mice compared to the normal control group. Intravitreal injection of FH535 effectively reduced Wnt5a protein expression. Both FH535 and Box5 effectively attenuated subretinal fibrosis and EMT, as well as the activation of β-catenin in laser-induced CNV mice, as evidenced by the significant reduction in areas positive for fibronectin, alpha-smooth muscle actin (α-SMA), collagen I, and active β-catenin labeling. In vitro, Wnt5a/ROR1, active β-catenin, and some other Wnt signaling molecules were upregulated in the TGFβ1-induced EMT cell model using ARPE-19 cells. Co-treatment with FH535, Box5, or Wnt5a shRNA markedly suppressed the activation of Wnt5a, nuclear translocation of active β-catenin, as well as the EMT in TGFβ1-treated ARPE-19 cells. Conversely, treatment with Foxy-5 independently resulted in the activation of abovementioned molecules and subsequent induction of EMT in ARPE-19 cells.
Conclusions
Our study reveals a reciprocal activation between Wnt5a and β-catenin to mediate EMT as a pivotal driver of subretinal fibrosis in nAMD. This positive feedback loop provides valuable insights into potential therapeutic strategies to treat subretinal fibrosis in nAMD patients.
Journal Article
Melatonin Maintains Inner Blood–Retinal Barrier by Regulating Microglia via Inhibition of PI3K/Akt/Stat3/NF-κB Signaling Pathways in Experimental Diabetic Retinopathy
Microglial activation and melatonin protection have been reported in diabetic retinopathy (DR). Whether melatonin could regulate microglia to protect the inner blood–retinal barrier (iBRB) remains unknown. In this study, the role of microglia in iBRB breakdown and the mechanisms of melatonin’s regulation on microglia were explored. In diabetic rat retinas, activated microglia proliferated and migrated from the inner retina to the outer retina, accompanied by the obvious morphological changes. Meanwhile, significant leakage of albumin was evidenced at the site of close interaction between activated microglia and the damaged pericytes and endothelial cells. In vitro , inflammation-related cytokines, such as tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and arginase-1 (Arg-1), were increased significantly in CoCl 2 -treated BV2 cells. The supernatant derived from CoCl 2 -treated BV2 cells significantly decreased the cell viability and disrupted the junctional proteins in both pericytes and endothelial cells, resulting in severe leakage. Melatonin suppressed the microglial overactivation, i.e., decreasing the cell number and promoting its anti-inflammatory properties in diabetic rat retinas. Moreover, the leakage of iBRB was alleviated and the pericyte coverage was restored after melatonin treatment. In vitro , when treated with melatonin in CoCl 2 -treated BV2 cells, the inflammatory factors were decreased, while the anti-inflammatory factors were increased, further reducing the pericyte loss and increasing the tight junctions. Melatonin deactivated microglia via inhibition of PI3K/Akt/Stat3/NF-κB signaling pathways, thus maintaining the integrity of iBRB. The present data support a causal role for activated microglia in iBRB breakdown and highlight the therapeutic potential of melatonin in the treatment of DR by regulating microglia.
Journal Article
بيان الدورة العامة الحادية عشرة للجنة المركزية المنبثقة عن المؤتمر الوطني الثامن للحزب الشيوعي الصيني : (أقر في 12 أغسطس-آب-عام 1966)
عقدت الدورة العامة الحادية عشرة للجنة المركزية المنبثقة عن المؤتمر الوطني الثامن للحزب الشيوعي الصيني في بكين من 1 الى 12 أغسطس (آب) عام 1966، وقد ترأس الدورة العامة الحادية عشرة الرفيق ماو تسي تونغ، وحضرها أعضاء اللجنة المركزية وأعضاؤها المرشحون : وحضرها كذلك الرفاق من مختلف المكاتب الاقليمية للجنة المركزية ومن لجان الحزب في المقاطعات والبلديات والمناطق ذات الحكم الذاتي وأعضاء فرقة الثورة الثقافية للجنة المركزية والرفاق في الدوائر المعنية للجنة المركزية وممثلو المدرسين والطلاب الثوريين في الجامعات والمعاهد العليا بالعاصمة . وقد أقرت الدورة العامة الحادية عشرة بعد المناقشة « قرار اللجنة المركزية للحزب الشيوعي الصيني حول الثورة الثقافية البروليتارية الكبرى » . كما صادقت الدورة العامة بعد النقاش على القرارات السياسية المهمة والاجراءات المهمة فيما يختص بالمسائل الداخلية والخارجية التي أجازها المكتب السياسي للجنة المركزية منذ الدورة العامة العاشرة للجنة المركزية المنبثقة عن المؤتمر الوطني الثامن التي عقدت في سبتمبر (أيلول) عام 1962.
Book
Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease
Parkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier’s disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation.
Journal Article
Extreme Precipitation Strongly Impacts the Interaction of Skewness and Kurtosis of Annual Precipitation Distribution on the Qinghai–Tibetan Plateau
Characterizing extreme precipitation precisely is crucial for predicting vegetation response to drought or storms. However, current precipitation generators in vegetation models do not simulate the occurrence and amount of extreme precipitation well. This study examined the effects of extreme precipitation on the skewness, kurtosis, and skewness–kurtosis interaction of annual precipitation distribution. The examination was based on theoretical calculations and monitoring data from 78 meteorological stations on the Qinghai–Tibetan Plateau (QTP). The results showed that extreme precipitation generally increased the skewness and kurtosis of annual precipitation distribution. A higher mean annual precipitation amplified the effects of precipitation extremes on promoting skewness and kurtosis in normal distribution scenarios. In contrast, these effects tended to be saturated for scenarios of higher mean annual precipitation in probability-based distributions. A reduction of dry days in a year markedly intensified the interaction of the skewness and the kurtosis, while the skewness–kurtosis interaction weakened with decreased maximum daily precipitation in a year. Moreover, the effect of extreme precipitation on the skewness–kurtosis interaction was stronger in arid or low-altitude areas. This study illustrates the fact that considering the skewness and kurtosis of annual precipitation distributions will be very helpful for simulating extreme precipitation on the QTP in the future. This will allow us to better understand the impact of climate change on alpine plants.
Journal Article
Recent Advances in the Preparation and Application of Two-Dimensional Nanomaterials
Two-dimensional nanomaterials (2D NMs), consisting of atoms or a near-atomic thickness with infinite transverse dimensions, possess unique structures, excellent physical properties, and tunable surface chemistry. They exhibit significant potential for development in the fields of sensing, renewable energy, and catalysis. This paper presents a comprehensive overview of the latest research findings on the preparation and application of 2D NMs. First, the article introduces the common synthesis methods of 2D NMs from both “top-down” and “bottom-up” perspectives, including mechanical exfoliation, ultrasonic-assisted liquid-phase exfoliation, ion intercalation, chemical vapor deposition, and hydrothermal techniques. In terms of the applications of 2D NMs, this study focuses on their potential in gas sensing, lithium-ion batteries, photodetection, electromagnetic wave absorption, photocatalysis, and electrocatalysis. Additionally, based on existing research, the article looks forward to the future development trends and possible challenges of 2D NMs. The significance of this work lies in its systematic summary of the recent advancements in the preparation methods and applications of 2D NMs.
Journal Article