Schottky Junction Enhanced Photosynthesis of Hydrogen Peroxide by Ultrathin Porous Carbon Nitride Supported Ni Nanoparticles.

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

Study on the role of MYCN in retinoblastoma by inhibiting p53 and activating wnt/ßcatenin/Fra-1 signaling pathway by reducing DKK3.

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive. In the present study, the expression of MYCN was either overexpressed or interfered in RB cells. Subsequently, the expression level of DKK3 was assessed through quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was evaluated using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell cycle progression and apoptosis were analyzed by flow cytometry and western blot analysis, respectively. Additionally, the expression of proteins involved in the Wnt/ß-catenin/Fra-1/p53 signaling pathway was evaluated via western blot analysis. To gain further insights, Wnt agonists and the P53 inhibitor PFT-α were introduced into exploration. The current investigation revealed a negative correlation between the expression levels of MYCN and DKK3 in RB cells. Additionally, DKK3 overexpression inhibited cell proliferation, promoted cell apoptosis, and arrested cell cycle in RB cells with high expression of MYCN. Moreover, enhanced DKK3 expression inhibited proliferation, promoted cell cycle arrest and apoptosis of RB cells by modulating the wnt/ßcatenin/Fra-1/p53 signaling pathway. Furthermore, in vivo experiments revealed that overexpression of DKK3 inhibits the growth of RB tumors. Collectively, our findings elucidate that MYCN stimulates the Wnt/ß-catenin/Fra-1 pathway by suppressing DKK3 expression, ultimately suppressing p53 activity and contributing to malignant progression of RB.

5α-Hydroxycostic acid inhibits choroidal neovascularization in rats through a dual signalling pathway mediated by VEGF and angiopoietin 2.

BACKGROUND: 5α-Hydroxycostic acid is a eudemane sesquiterpene that is isolated from the natural plant, Laggera alata. It exerts anti-inflammatory and anti-angiogenic effects on human breast cancer cells, but its role and underlying mechanism in choroidal neovascularization (CNV) are still unclear. We conducted a study to verify that 5α-Hydroxycostic acid can inhibit the formation and leakage of CNV, and describe the possible dual pathway by which it exerts its inhibitory effects in this process. METHODS: An in vitro model of choroidal neovascularization was established using VEGF164, while a rat model of choroidal neovascularization was established using a 532 nm laser. In both models, the effects of 5α-Hydroxycostic acid in vivo and in vitro were evaluated to determine its inhibitory effect on abnormal cell proliferation, migration and tubule formation, as well as its effect on pathological changes in choroidal tissues and the area of neovascularization leakage in rats. The levels of components in the VEGF/VEGFR and Ang2/Tie2 signaling pathways were measured in tissues and cells. RESULTS: In vitro experiments have shown that 5α-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5α-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5α-Hydroxycostic acid has a positive therapeutic effect on choroidal neovascularization in rats. It can effectively reduce vascular leakage, consistent with the results of the cell experiments. CONCLUSION: 5α-Hydroxycostic acid can inhibit choroidal neovascularization by interfering with the VEGF- and Ang2/Tie2-related pathways, and it may be a good candidate drug for treating CNV.

Comorbidity and drug resistance of smear-positive pulmonary tuberculosis patients in the yi autonomous prefecture of China: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) has a high morbidity and mortality rate, and its prevention and treatment focus is on impoverished areas. The Liangshan Yi Autonomous Prefecture is a typical impoverished area in western China with insufficient medical resources and high HIV positivity. However, there have been few reports of TB and drug resistance in this area. METHODS: We collected the demographic and clinical data of inpatients with sputum smear positive TB between 2015 and 2021 in an infectious disease hospital in the Liangshan Yi Autonomous Prefecture. Descriptive analyses were used for the epidemiological data. The chi-square test was used to compare categorical variables between the drug-resistant and drug-susceptible groups, and binary logistic regression was used to analyse meaningful variables. RESULTS: We included 2263 patients, 79.9% of whom were Yi patients. The proportions of HIV (14.4%) and smoking (37.3%) were higher than previously reported. The incidence of extrapulmonary TB (28.5%) was high, and the infection site was different from that reported previously. When drug resistance gene detection was introduced, the proportion of drug-resistant patients became 10.9%. Patients aged 15-44 years (OR 1.817; 95% CI 1.162-2.840; P < 0.01) and 45-59 years (OR 2.175; 95% CI 1.335-3.543; P < 0.01) had significantly higher incidences of drug resistance than children and the elderly. Patients with a cough of ≥ 2 weeks had a significantly higher chance of drug resistance than those with < 2 weeks or no cough symptoms (OR 2.069; 95% CI 1.234-3.469; P < 0.01). Alcoholism (OR 1.741; 95% CI 1.107-2.736; P < 0.05) and high bacterial counts on sputum acid-fast smears (OR 1.846; 95% CI 1.115-3.058; P < 0.05) were significant in the univariate analysis. CONCLUSIONS: Sputum smear-positive TB predominated in Yi men (15-44 years) with high smoking, alcoholism, and HIV rates. Extrapulmonary TB, especially abdominal TB, prevailed. Recent drug resistance testing revealed higher rates in 15-59 age group and ≥ 2 weeks cough duration. Alcohol abuse and high sputum AFB counts correlated with drug resistance. Strengthen screening and supervision to curb TB transmission and drug-resistant cases in the region.

Biophysical characterization and in vitro imaging of carbonized MOFs.

Nanoparticles have been widely used in biological imaging and treatments of various diseases, especially for studies of tumors, due to their high efficiency in drug delivery and many other functions. Metal-organic frameworks have been an important research area in recent years because of advantages such as large apertures, adjustable structural compositions, adjustable sizes, multifunctionality, high drug loading, good biocompatibility and so on, and they show promise as multifunctional drug carriers. In this study, a carbonized MOF with photothermal therapeutic potential and dual-mode imaging capability was prepared. The biophysical properties of MIL-100 and C-MIL nanoparticles were determined, such as particle size, zeta potential and saturation magnetization strength. CCK-8 cell assays and mouse HE sections confirmed that C-MIL nanoparticles have good in vitro and in vivo biocompatibility. The solution temperature of C-MIL nanoparticles reached 58.1 °C during sustained laser irradiation at 808 nm, which confirmed the photothermal potential of the nanoparticles. Moreover, in biological imaging, C-MIL nanoparticles showed the ability to support in vitro nuclear magnetic and photoacoustic dual-mode imaging. C-MIL nanoparticles provide new options for tumor therapy, drug delivery and biological imaging.

The application prospects of honokiol in dermatology.

Honokiol is one of the natural extracts of Magnolia officinalis. It is a small molecule, lipophilic compound with extensive biological effects. It has been used in the treatment of multisystem diseases, including digestive diseases, endocrine diseases, nervous system diseases, and various tumors. This paper reviews the biological effects of honokiol on the treatment of skin diseases in recent years, including anti-microbial, anti-oxidant, anti-inflammatory, anti-tumor, anti-fibrosis, anti-allergy, photo-protection, and immunomodulation. Most current researches are focused on the effects of anti-melanoma and photo-protection. Therefore, we summarized the specific mechanisms about these two effects. On the other side of treating skin diseases, the advantages of topical drugs cannot be replaced. As a small molecule fat-soluble compound, honokiol is suitable for external use. We reviewed the advantages and disadvantages of the topical mixed cream and various improved methods. These improvements include physical and chemical penetration enhancers, drug carriers, and chemical derivatives. In conclusion, honokiol has a wide range of effects, and its topical preparation provides a safe and effective way for treating skin diseases.

Synthesis of Silver Nanoparticles-Modified Graphitic Carbon Nitride Nanosheets for Highly Efficient Photocatalytic Hydrogen Peroxide Evolution.

As a promising metal-free photocatalyst, graphitic carbon nitride (g-C3N4) is still limited by insufficient visible light absorption and rapid recombination of photogenerated carriers, resulting in low photocatalytic activity. Here, we adjusted the microstructure of the pristine bulk-g-C3N4 (PCN) and further loaded silver (Ag) nanoparticles. Abundant Ag nanoparticles were grown on the thin-layer g-C3N4 nanosheets (CNNS), and the Ag nanoparticles decorated g-C3N4 nanosheets (Ag@CNNS) were successfully synthesized. The thin-layer nanosheet-like structure was not only beneficial for the loading of Ag nanoparticles but also for the adsorption and activation of reactants via exposing more active sites. Moreover, the surface plasmon resonance (SPR) effect induced by Ag nanoparticles enhanced the absorption of visible light by narrowing the band gap of the substrate. Meanwhile, the composite band structure effectively promoted the separation and transfer of carriers. Benefiting from these merits, the Ag@CNNS reached a superior hydrogen peroxide (H2O2) yield of 120.53 µmol/g/h under visible light irradiation in pure water (about 8.0 times higher than that of PCN), significantly surpassing most previous reports. The design method of manipulating the microstructure of the catalyst combined with the modification of metal nanoparticles provides a new idea for the rational development and application of efficient photocatalysts.

Protective effects of 4-octyl itaconate against inflammatory response in angiotensin II-induced oxidative stress in human primary retinal pigment epithelium.

4-octyl itaconate (OI) is one kind of cell-permeable derivative of itaconate to regulate inflammation and oxidative stress. However, its effects on the angiotensin II (Ang II)-induced inflammatory response and oxidative stress in human primary retinal pigment epithelium (hRPE) cells as well as its underlying mechanisms were unclear. In this study, we found that OI suppressed changes in pro-inflammatory cytokines (MCP-1, IL-8, and IL-6) and reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) via activation of Nrf2 signaling in Ang II-treated hRPE cells. A total of 645 differentially expressed long non-coding RNAs (lncRNAs) and 455 mRNAs were identified by microarray analysis. Ten lncRNAs were analyzed using the Coding-non-coding gene co-expression (CNC) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, revealing that many differentially expressed lncRNAs were enriched in immune response-related pathways, such as IL-17, TNF, and NOD-like receptor signaling. This finding suggested that OI inhibits Ang II-induced inflammatory response and oxidative stress by activating Nrf2 signaling in hRPE cells. We also provided a novel perspective on the role of lncRNAs in the protective effects of OI.

Moderate oxidative stress promotes epithelial-mesenchymal transition in the lens epithelial cells via the TGF-ß/Smad and Wnt/ß-catenin pathways.

The epithelial-mesenchymal transition (EMT) plays a significant role in fibrosis and migration of lens epithelial cells (LECs), and eventually induces posterior capsule opacification (PCO). In the past, it was generally believed that the TGF-ß/Smad pathway regulates lens EMT. A recent study found that attenuated glutathione level promotes LECs EMT via the Wnt/ß-catenin pathway, which suggests a more complex pathogenesis of PCO. To test the hypothesis, we used the mouse cataract surgery PCO model and tested both canonical Wnt/ß-catenin and TGF-ß/Smad signaling pathways. The results showed that both TGF-ß/Smad and Wnt/ß-catenin pathways were activated during the lens capsule fibrosis. Compared with the freshly isolated posterior capsule, the expression level of phosphorylated Smad2 was highest at day3 and then slightly decreased, but the expression level of Wnt10a gradually increased from day0 to day7. It shows that these two pathways are involved in the lens epithelium's fibrotic process and may play different roles in different periods. Subsequently, we established oxidative stress-induced EMT model in primary porcine lens epithelial cells and found that both the TGF-ß/Smad and Wnt/ß-catenin pathways were activated. Further study suggests that block Wnt/ß-catenin pathway using XAV939 alone or block TGF-ß/Smad pathway using LY2109761 could partially block pLECs fibrosis, but blocking Wnt/ß-catenin and TGF-ß/Smad pathway using combined XAV939 and LY2109761 could completely block pLECs fibrosis. In conclusion, this study demonstrates that both TGF-ß/Smad and canonical Wnt/ß-catenin pathways play a significant role in regulating epithelial-mesenchymal transformation of lens epithelial cells but might be in a different stage.

Analysis of genetic polymorphisms for age-related macular degeneration (AMD) in Chinese Tujia ethnic minority group.

BACKGROUND: Age-related macular degeneration (AMD) can cause vision loss or blindness in elderly. The associations between single nucleotide polymorphism (SNP) and AMD in Chinese Tujia ethnic minority group are still unclear. METHODS: A total of 2122 Tujia volunteers were recruited and 197 of them were diagnosed with AMD (either dry or wet type).Then the blood specimens of these 197 AMD patients and 404 controls from the remaining 1925 normal Tujia volunteers were collected to detect the frequencies of 39 chosen SNPs. The Bonferroni method was used to correct the P values from the Fisher's exact test. RESULTS: The mean age of the 197 AMD patients(113 males and 84 females) was 68.4197 years old. No significant differences in allelic and genotypic frequencies were found for all the 39 SNPs between the patients and controls. However, weak correlations between 10 SNPs (CFH rs1329428 TT genotype, CFH rs3753394 CC genotype and T allele, CFH rs1410996 AA genotype, CFH rs800292 AA genotype, CFH rs800292 A allele, VEGF rs833061 TT genotype and C allele, VEGF rs2010963 CG genotype, VEGFR2 rs1531289 TT genotype, ARMS2 rs10490924 TT genotype, KCTD10 rs238104 GC genotype, rs1531289 T allele and ARMS2 rs10490924 T allele) and AMD were shown. CONCLUSIONS: The effects of 39 SNPs have found no associations with the morbidity of AMD in Chinese Tujia ethnic minority group.

Chitosan inhibits inflammation and adipogenesis of orbital fibroblasts in Graves ophthalmopathy.

Purpose: The aim of this study was to investigate the roles of chitosan in inflammation and adipogenesis of primary cultured orbital fibroblasts in Graves ophthalmopathy (GO). Methods: Cell viability, apoptosis, and cell cycle were determined with the Cell Counting Kit-8 (CCK-8), the Annexin V-FITC/PI kit, and flow cytometry, respectively. Inflammation of orbital fibroblasts was stimulated by interleukin-1 beta (IL-1ß). The levels of IL-6 and prostaglandin E-2 (PGE-2) were measured using an enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) was measured with real-time PCR and western blot assay. Phosphorylation of c-Jun N-terminal kinase (JNK) was evaluated with western blot assay. An inhibitor of JNK was used to investigate the signal transduction pathway of cytokine production. Orbital fibroblasts differentiated to adipose cells in differentiation medium. Adipose cells were dyed with Oil Red O. FABP4, adiponectin, C/EBPα, PPAR-γ, and phosphorylation of AKT were evaluated with western blot assay. Results: The results showed that IL-1ß statistically significantly increased the expression of IL-6, PGE-2, and COX-2 in orbital fibroblasts. Phosphorylation of JNK was promoted by IL-1ß. IL-6 and PGE-2 were modulated by the JNK signaling pathway as determined with the inhibition experiments. Chitosan downregulated expression of IL-1ß-stimulated IL-6, COX-2, and PGE-2 and downregulated phosphorylation of JNK. Chitosan inhibited the production of adipose cells dyed by Oil Red O. Chitosan statistically significantly decreased the protein levels of FABP4, adiponectin, C/EBPα, and PPAR-γ with downregulation of AKT phosphorylation during adipocyte differentiation. Conclusions: Chitosan statistically significantly inhibits inflammation and adipogenesis, as well as related signaling pathways, of orbital fibroblasts in GO. This indicates a possible therapeutic effect of chitosan on Graves ophthalmopathy.

Expression and role of interleukin-9 in Vogt-Koyanagi-Harada disease.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disease that can lead to blindness. This study was designed to investigate whether interleukin (IL)-9 plays a role in the development of VKH disease. METHODS: IL-9, IL-17, and interferon (IFN)-γ levels, present in the supernatants of cultured peripheral blood mononuclear cells (PBMCs) and CD4+T cells, were assessed with enzyme-linked immunosorbent assay. IL-9 mRNA expression in PBMCs was measured with real-time quantitative PCR. The proliferation of PBMCs in response to different doses of recombinant human IL-9 (rIL-9) was measured using the Cell Counting Kit-8 assay. RESULTS: IL-9 mRNA levels in PBMCs were statistically significantly elevated in patients with active VKH disease compared to those in patients with inactive VKH disease (p<0.05) and normal controls (p<0.05). Statistically significantly higher expression of IL-9 was observed in the supernatants of stimulated PBMCs (p<0.01) and CD4+ T cells (p<0.01) from patients with active VKH disease compared to that in cells from patients with inactive VKH disease and normal controls. rIL-9 at a concentration of 100 ng/ml did not induce proliferation of PBMCs (p>0.05). After the PBMCs and CD4+ T cells were stimulated with rIL-9 (100 ng/ml), the secretion of IL-17 was increased statistically significantly (p<0.05), whereas the level of IFN-γ was not statistically significantly altered (p>0.05). CONCLUSIONS: These findings suggest that IL-9 is involved in the pathogenesis of VKH disease, and that IL-9 might also enhance the inflammatory response by increasing the secretion of IL-17, an established proinflammatory cytokine in VKH disease. Manipulation of IL-9 could represent a novel option for the treatment of VKH disease.

Association of Two Polymorphisms, rs1061170 and rs1410996, in Complement Factor H with Age-Related Macular Degeneration in an Asian Population: A Meta-Analysis.

BACKGROUND: With the increasing number of studies indicating that two single-nucleotide polymorphisms (SNPs), rs1061170 and rs1410996, in complement factor H (CFH) might be associated with the susceptibility to age-related macular degeneration (AMD), the exact association still remains uncertain. Thus, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and the AMD risk particularly in an Asian population. METHODS: A systematic search of studies on the association of two SNPs with the susceptibility to AMD was conducted in PubMed, Embase and Web of Science. Summary odds ratios (ORs) and 95% confidence intervals (CIs) of allele contrast and genotype contrast were estimated using the random or fixed effects model. The Q statistic test was used to identify heterogeneity, and the funnel plot was adopted to evaluate publication bias. A total of 19 case-control studies on rs1061170 and 8 studies on rs1410996 were included. RESULTS: Clearly a significantly increased trend of AMD was observed with the rs1061170 (T vs. C: OR = 1.91, 95% CI = 1.71-2.13, pH = 0.029; TC vs. CC: OR = 2.11, 95% CI = 1.30-3.42, pH = 0.792; TT vs. CC: OR = 3.90, 95% CI = 2.45-6.22, pH = 0.774). Similarly, the rs1410996 polymorphism also showed a rising AMD tendency (T vs. C: OR = 1.48, 95% CI = 1.17-1.87, pH < 0.001; TC vs. CC: OR = 1.52, 95% CI = 1.13-2.04, pH = 0.002; TT vs. CC: OR = 2.10, 95% CI = 1.27-3.49, pH < 0.001). What is more, subgroup analysis revealed that both polymorphisms indicated a high risk of nAMD (neovascular AMD) in Asian populations. CONCLUSIONS: This meta-analysis suggested that CFH rs1061170 and rs1410996 polymorphisms were associated with AMD risk, both of which demonstrated a higher susceptibility to AMD, especially to nAMD. However, the results of rs1410996 should be interpreted with caution due to the limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.

Experimental endostatin-GFP gene transfection into human retinal vascular endothelial cells using ultrasound-targeted cationic microbubble destruction.

PURPOSE: The purpose of this study was to investigate whether ultrasound-targeted cationic microbubble destruction could effectively deliver endostatin-green fluorescent protein (ES-GFP) plasmids to human retinal vascular endothelial cells (HRECs). METHODS: Cationic microbubbles (CMBs) were prepared and then compared with neutral microbubbles (NMBs) and liposomes. First, the two types of microbubbles were characterized in terms of size and zeta potential. The cell viability of the HRECs was measured using the 3-(4,5-dimthylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) assay. The transcription and expression of endostatin, VEGF, Bcl-2, and Bcl-xl were measured via quantitative real-time PCR (qPCR) and western blotting, respectively. RESULTS: CMBs differed significantly from NMBs in terms of the zeta potential, but no differences in size were detected. Following ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy, the transcription and expression of endostatin were highest in the CMB group (p<0.05), while the transcription and expression of VEGF, Bcl-2, and Bcl-xl were lowest compared with the other groups. Moreover, the inhibition of HREC growth was enhanced following treatment with CMBs compared with NMBs or liposomes in vitro (p<0.01). CONCLUSIONS: This study demonstrated that ultrasound-mediated cationic microbubbles could enhance the transfection efficiency of ES-GFP, which had obvious impacts on the inhibition of the growth process of HRECs in vitro. These results suggest that the combination of UTMD and ES-GFP compounds might be a useful tool for gene therapy targeting retinal neovascularization.

Power system fault diagnosis with quantum computing and efficient gate decomposition.

Power system fault diagnosis is crucial for identifying the location and causes of faults and providing decision-making support for power dispatchers. However, most classical methods suffer from significant time-consuming, memory overhead, and computational complexity issues as the scale of the power system concerned increases. With rapid development of quantum computing technology, the combinatorial optimization method based on quantum computing has shown certain advantages in computational time over existing methods. Given this background, this paper proposes a quantum computing based power system fault diagnosis method with the quantum approximate optimization algorithm. The proposed method reformulates the fault diagnosis problem as a Hamiltonian by using Ising model, which completely preserves the coupling relationship between faulty components and various operations of protective relays and circuit breakers. Additionally, to enhance problem-solving efficiency under current equipment limitations, the symmetric equivalent decomposition method of multi-z-rotation gate is utilized. Furthermore, the small probability characteristics of power system events is utilized to reduce the number of qubits. Simulation results based on the test system show that the proposed methods can achieve the same optimal results with a faster speed compared with the classical higher-order solver provided by D-Wave.

NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway.

Introduction: This study examined the impact of 5'-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both in vivo and in vitro. Methods: Enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB). Results: FCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kß pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations. Conclusion: NECA could impair DCs' ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.

Extension domain of amyloid processor protein inhibits amyloidogenic cleavage and balances neural activity in a traumatic brain injury mouse model.

BACKGROUND: Mechanisms underlying cognitive dysfunction following traumatic brain injury (TBI) partially due to abnormal amyloid processor protein (APP) cleavage and neural hyperactivity. Binding of the extension domain of APP (ExD17) to the GABAbR1 receptor results in reduced neural activity, which might play a role in the mechanisms of cognitive dysfunction caused by TBI. METHODS: Stretch-induced injury was utilized to establish a cell injury model in HT22 cells. The TBI model was created by striking the exposed brain tissue with a free-falling weight. Topical or intraperitoneal administration of ExD17 was performed. Cell viability was assessed through a cell counting kit-8 assay, while intracellular Ca2+ was measured using Fluo-4. Western blotting was used to investigate the expression of APP amyloidogenic cleavage proteins, GABAbR1, phospholipase C (PLC), PLCB3, and synaptic proteins. ELISA was performed to analyze the levels of Aß42. Seizures were assessed using electroencephalography (EEG). Behaviors were evaluated through the novel object recognition test, open field test, elevated plus maze test, and nest-building test. RESULTS: ExD17 improved cell viability and reduced intracellular calcium in the cell injury model. The treatment also suppressed the increased expression of APP amyloidogenic cleavage proteins and Aß42 in both cell injury and TBI models. ExD17 treatment reversed the abnormal expression of GABAbR1, GRIA2, p-PLCG1/PLCG1 ratio, and p-PLCB3/PLCB3 ratio. In addition, ExD17 treatment reduced neural activity, seizure events, and their duration in TBI. Intraperitoneal injection of ExD17 improved behavioral outcomes in the TBI mouse model. CONCLUSIONS: ExD17 treatment results in a reduction of amyloidogenic APP cleavage and neuroexcitotoxicity, ultimately leading to an improvement in the behavioral deficits observed in TBI mice.

Efficacy and Safety of Dupilumab in Older Patients (Aged 80 Years and Above) with Atopic Dermatitis: A Prospective Study.

BACKGROUND: Atopic dermatitis presents unique challenges in the older population owing to age-related changes in skin barrier function and immune regulation. However, there is limited evidence on the efficacy and safety of dupilumab, an anti-interleukin-4Rα monoclonal antibody, in patients with atopic dermatitis aged 80 years and above. OBJECTIVE: We aimed to assess the clinical efficacy and safety of dupilumab treatment in patients with atopic dermatitis aged 80 years and above. METHODS: Twenty-eight older patients received dupilumab and were evaluated based on several clinical parameters, including the Eczema Area and Severity Index (EASI), Numeric Rating Scale (NRS), Dermatology Life Quality Index (DELI), and AD Control Tool (ACT). Safety assessments and monitoring of concomitant medication use were conducted. RESULTS: Twenty-six patients completed 16 weeks of treatment, 13 completed 28 weeks, and two completed more than 36 weeks. Dupilumab treatment resulted in a significant improvement in atopic dermatitis symptoms after 16 weeks as demonstrated by reduced EASI, NRS, DLQI, and ADCT scores. Dupilumab had no significant impact on underlying diseases or medication use. No common adverse reactions, such as conjunctivitis and erythema of the face and neck, were identified. Among the 26 patients receiving dupilumab treatment during the COVID-19 pandemic, 17 remained uninfected or experienced milder COVID-19 symptoms than experienced in the general population. CONCLUSIONS: Dupilumab treatment showed significant efficacy in improving atopic dermatitis symptoms in patients aged 80 years and above with a high level of safety. Larger long-term clinical trials are needed to validate these results and provide further evidence for the use of dupilumab in older patients with atopic dermatitis.

Dupilumab and the potential risk of eosinophilic pneumonia: case report, literature review, and FAERS database analysis.

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/µl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.

Targeted long-term noninvasive treatment of choroidal neovascularization by biodegradable nanoparticles.

Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. STATEMENT OF SIGNIFICANCE: This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration.