Label-Free Proteomics Reveals Decreased Expression of CD18 and AKNA in Peripheral CD4+ T Cells from Patients with Vogt-Koyanagi-Harada Syndrome

Vogt-Koyanagi-Harada (VKH) syndrome is a systemic autoimmune disease. CD4+ T cells have been shown to be involved in autoimmune diseases including VKH syndrome. To screen aberrantly expressed membrane proteins in CD4+ T cell from patients with active VKH syndrome, blood samples were taken from five patients with active VKH syndrome and five healthy individuals. A label-free quantitative proteomic strategy was used to identify the differently expressed proteins between the two groups. The results revealed that the expression of 102 peptides was significantly altered (p<0.05) between two groups and matched amino acid sequences of proteins deposited in the international protein index (ipi.HUMAN.v3.36.fasta). The identified peptides corresponded to 64 proteins, in which 30 showed more than a 1.5-fold difference between the two groups. The decreased expression of CD18 and AKNA transcription factor (AKNA), both being three-fold lower than controls in expression identified by the label-free method, was further confirmed in an additional group of five active VKH patients and six normal individuals using the Western blot technique. A significantly decreased expression of CD18 and AKNA suggests a role for both proteins in the pathogenesis of this syndrome

The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals

The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies of the Fat1 protocadherin. Fat1 expression in VSMCs increases significantly after arterial injury or growth factor stimulation. Fat1 knockdown decreases VSMC migration in vitro, but surprisingly, enhances cyclin D1 expression and proliferation. Despite limited similarity to classical cadherins, the Fat1 intracellular domain (Fat1IC) interacts with β-catenin, inhibiting both its nuclear localization and transcriptional activity. Fat1 undergoes cleavage and Fat1IC species localize to the nucleus; however, inhibition of the cyclin D1 promoter by truncated Fat1IC proteins corresponds to their presence outside the nucleus, which argues against repression of β-catenin–dependent transcription by nuclear Fat1IC. These findings extend recent observations about Fat1 and migration in other cell types, and demonstrate for the first time its anti-proliferative activity and interaction with β-catenin. Because it is induced after arterial injury, Fat1 may control VSMC functions central to vascular remodeling by facilitating migration and limiting proliferation

The traditional Chinese medicine and non-small cell lung cancer: from a gut microbiome perspective

Non-small cell lung cancer (NSCLC) is one of the most serious diseases affecting human health today, and current research is focusing on gut flora. There is a correlation between intestinal flora imbalance and lung cancer, but the specific mechanism is not clear. Based on the “lung and large intestine being interior-exteriorly related” and the “lung-intestinal axis” theory. Here, based on the theoretical comparisons of Chinese and western medicine, we summarized the regulation of intestinal flora in NSCLC by active ingredients of traditional Chinese medicine and Chinese herbal compounds and their intervention effects, which is conducive to providing new strategies and ideas for clinical prevention and treatment of NSCLC

A polymorphism in porcine miR-22 is associated with pork color

MicroRNAs (miRNAs) are posttranscriptional regulators that play key roles in meat color regulation. Changes in miRNA expression affect their target mRNAs, leading to multifunctional effects on biological processes and phenotypes. In this study, a G &gt; A mutation site located upstream of the precursor miR-22 sequence in Suhuai pigs was significantly correlated with the meat color parameter a*(redness) of the porcine longissimus dorsi (LD) muscle. AA genotype individuals had the highest average meat color a* value and the lowest miR-22 level. When G &gt; A mutation was performed in the miR-22 overexpression vector, miR-22 expression significantly decreased. Considering that Ca2+ homeostasis is closely related to pig meat color, our results further demonstrated that ELOVL6 is a direct target of miR-22 in pigs. The effects of miR-22 on skeletal muscle intracellular Ca2+ were partially caused by the suppression of ELOVL6 expression

Ultra-broadband near-field Josephson microwave microscopy

Advanced microwave technologies constitute the foundation of a wide range of modern sciences, including quantum computing, microwave photonics, spintronics, etc. To facilitate the design of chip-based microwave devices, there is an increasing demand for state-of-the-art microscopic techniques capable of characterizing the near-field microwave distribution and performance. In this work, we integrate Josephson junctions onto a nano-sized quartz tip, forming a highly sensitive microwave mixer on-tip. This allows us to conduct spectroscopic imaging of near-field microwave distributions with high spatial resolution. Leveraging its microwave-sensitive characteristics, our Josephson microscope achieves a broad detecting bandwidth of up to 200 GHz with remarkable frequency and intensity sensitivities. Our work emphasizes the benefits of utilizing the Josephson microscope as a real-time, non-destructive technique to advance integrated microwave electronics

Folic acid therapy reduces the first stroke risk associated with hypercholesterolemia among hypertensive patients

Background and Purpose - We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. Methods - A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. Results - The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥ 200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (\u3c200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first s roke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84 P\u3c0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). Conclusions - Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases

Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice

Nano-antibodies possess great potential in many applications. However, they are naturally derived from heavy chain-only antibodies (HcAbs), which lack light chains and the CH1 domain, and are only found in camelids and sharks. In this study, we investigated whether the precise genetic removal of the CH1 exon of the γ1 gene enabled the production of a functional heavy chain-only IgG1 in mice. IgG1 heavy chain dimers lacking associated light chains were detected in the sera of the genetically modified mice. However, the genetic modification led to decreased expression of IgG1 but increased expression of other IgG subclasses. The genetically modified mice showed a weaker immune response to specific antigens compared with wild type mice. Using a phage-display approach, antigen-specific, single domain VH antibodies could be screened from the mice but exhibited much weaker antigen binding affinity than the conventional monoclonal antibodies. Although the strategy was only partially successful, this study confirms the feasibility of producing desirable nano-bodies with appropriate genetic modifications in mice

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment