Arachidonic acid alleviates autoimmune diabetes in NOD mice.

BACKGROUND: Arachidonic acid (AA) is considered to link nutrient metabolism, to inflammation and immunity, suggesting it may have a role in autoimmune diseases. Our previous study suggests that DPP-4 inhibitors (DPP-4i) might regulate AA - relative signaling in type 1 diabetes. AIMS: To examine the effect of AA on autoimmune diabetes and its cross-talk with DPP-4i in The Non-Obese Diabetic (NOD) mice. METHODS: The NOD mice were divided randomly and equally into three groups: AA group, AA plus DPP-4i group and control group. The incidence of diabetes, blood glucose, insulitis and cytokine profiles were monitored. At the end of the experiment, pancreatic tissues were stained by H&E. Serum cytokine profiles were examined using a Mesco Scale Discovery multiplexed-assay kit. RESULTS: Even though AA or AA plus DPP-4i treatment has no effect on incidence of diabetes and weight, AA treatment reduces blood glucose, preserves islet morphology and alleviates inflammatory cell infiltration into pancreatic islets in NOD mice, accompanying with increased serum levels of IL-10, IL-1 ß, IL-6, IL-5, KC/GRO and TNF-α and decreased serum levels of IL-2. CONCLUSION: We observed that AA treatment alleviates autoimmune diabetes in NOD mice by reducing hyperglycemia, alleviating insulitis and improving cytokine profiles. DPP-4i might alleviate the effect of AA by cross-talk. We provide evidence of AA treatment to alleviate type 1 diabetes in NOD mice, which may provide a novel therapeutic option for type 1 diabetes.

Chemically Driven Sintering of Colloidal Cu Nanocrystals for Multiscale Electronic and Optical Devices.

Emerging applications of Internet of Things (IoT) technologies in smart health, home, and city, in agriculture and environmental monitoring, and in transportation and manufacturing require materials and devices with engineered physical properties that can be manufactured by low-cost and scalable methods, support flexible forms, and are biocompatible and biodegradable. Here, we report the fabrication and device integration of low-cost and biocompatible/biodegradable colloidal Cu nanocrystal (NC) films through room temperature, solution-based deposition, and sintering, achieved via chemical exchange of NC surface ligands. Treatment of organic-ligand capped Cu NC films with solutions of shorter, environmentally benign, and noncorrosive inorganic reagents, namely, SCN- and Cl-, effectively removes the organic ligands, drives NC grain growth, and limits film oxidation. We investigate the mechanism of this chemically driven sintering by systemically varying the Cu NC size, ligand reagent, and ligand treatment time and follow the evolution of their structure and electrical and optical properties. Cl--treated, 4.5 nm diameter Cu NC films yield the lowest DC resistivity, only 3.2 times that of bulk Cu, and metal-like dielectric functions at optical frequencies. We exploit the high conductivity of these chemically sintered Cu NC films and, in combination with photo- and nanoimprint-lithography, pattern multiscale structures to achieve high-Q radio frequency (RF) capacitive sensors and near-infrared (NIR) resonant optical metasurfaces.

Poor Prognostic Biomarker KIAA1522 Is Associated with Immune Infiltrates in Hepatocellular Carcinoma.

Background: The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. Objective: To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Methods: Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Results: Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. Conclusion: High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.

Downregulation of Kcnq1ot1 attenuates ß-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis.

AIM: To examine the effect of lncRNA Kcnq1ot1 on pancreatic ß cells in the development of diabetes. METHODS: The expression levels of Kcnq1ot1 were detected in the islets of diabetes mouse models and the serum of patients with type 2 diabetes by qRT-PCR. CCK8, Ki67 staining, immunohistochemical analyses, glucose-stimulated insulin secretion and intraperitoneal glucose tolerance test were performed to detect the effect of Kcnq1ot1 on ß-cell proliferation and insulin secretion in vitro and in vivo. The relationship between Kcnq1ot1 and miR-15b-5p was predicted by bioinformatics prediction, which was confirmed by luciferase reporter assay. RESULTS: Kcnq1ot1 was more abundant in the pancreas. The expression of Kcnq1ot1 was decreased in the islets of db/db mice and diet-induced obese mice and in the serum of patients with type 2 diabetes. Silencing Kcnq1ot1 inhibited the ß-cell proliferation concomitant with a reduction in the levels of Ccnd1 and Ccnd2. Insulin synthesis and secretion were impaired, along with the decreased expression of Ins1, Ins2, and insulin-related transcription factors. Moreover, Kcnq1ot1 knockdown in vivo reduced glucose tolerance and decreased insulin secretion, consistent with the reduction in the relative islet area and Ki67-positive ß-cells detected by immunochemistry and immunofluorescence staining, respectively. Mechanistically, Kcnq1ot1 directly targeted miR-15b-5p which regulated ß-cell proliferation and insulin secretion through Ccnd1 and Ccnd2. Notably, the suppression of miR-15b-5p attenuated the inhibition of Min6 proliferation and insulin production induced by Kcnq1ot1 knockdown. CONCLUSION: Kcnq1ot1 regulated ß-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis, which is worthy of further investigation considering its potential in diabetes treatment.

Downregulation of MCF2L Promoted the Ferroptosis of Hepatocellular Carcinoma Cells through PI3K/mTOR Pathway in a RhoA/Rac1 Dependent Manner.

Methods and Results: The levels of MCF2L were detected by PCR and western blotting assay. The effect of MCF2L on ferroptosis was confirmed by MTT, colony formation assay, Brdu, in vivo animal experiment, and the content of Iron, GSH, ROS, and MDA. The underlying mechanisms were explored by PCR, western blotting, and affinity precipitation assay. Our findings demonstrated that MCF2L is remarkedly upregulated in HCC tissues, and sorafenib can induce the levels of MCF2L, suggesting that MCF2L might function in sorafenib resistance of HCC. Further analysis showed that downregulation of MCF2L enhances HCC cell death induced by sorafenib, and ferroptosis inhibitor can reverse this process. Subsequent experiments showed that downregulation of MCF2L elevates the content of Iron, ROS, and MDA, which are all indicators of ferroptosis. Finally, mechanism analysis showed that MCF2L regulates the PI3K/AKT pathway in a RhoA/Rac1 dependent manner. Conclusions: Our study showed that targeting MCF2L may be a hopeful method to overcome sorafenib-resistance through inducing ferroptosis in HCC.

Identification of Diagnostic Markers in Infantile Hemangiomas.

Background: Infantile Hemangiomas (IHs) are common benign vascular tumors of infancy that may have serious consequences. The research on diagnostic markers for IHs is scarce. Methods: The "limma" R package was applied to identify differentially expressed genes (DEGs) in developing IHs. Plugin ClueGO in Cytoscape software performed functional enrichment of DEGs. The Search Tool for Retrieving Interacting Genes (STRING) database was utilized to construct the PPI network. The least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were used to identify diagnostic genes for IHs. The receiver operating characteristic (ROC) curve evaluated diagnostic genes' discriminatory ability. Single-gene based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by Gene Set Enrichment Analysis (GSEA). The chemicals related to the diagnostic genes were excavated by the Comparative Toxicogenomics Database (CTD). Finally, the online website Network Analyst was used to predict the transcription factors targeting the diagnostic genes. Results: A total of 205 DEGs were singled out from IHs samples of 6-, 12-, and 24-month-old infants. These genes principally participated in vasculogenesis and development-related, endothelial cell-related biological processes. Then we mined 127 interacting proteins and created a network with 127 nodes and 251 edges. Furthermore, LASSO and SVM-RRF algorithms identified five diagnostic genes, namely, TMEM2, GUCY1A2, ISL1, WARS, and STEAP4. ROC curve analysis results indicated that the diagnostic genes had a powerful ability to distinguish IHs samples from normal samples. Next, the results of GSEA for a single gene illustrated that all five diagnostic genes inhibited the "valine, leucine, and isoleucine degradation" pathway in the development of IHs. WARS, TMEM2, and STEAP4 activated the "blood vessel development" and "vasculature development" in IHs. Subsequently, inhibitors targeting TMEM2, GUCY1A2, ISL1, and STEAP4 were mined. Finally, 14 transcription factors regulating GUCY1A2, 14 transcription factors regulating STEAP4, and 26 transcription factors regulating ISL1 were predicted. Conclusion: This study identified five diagnostic markers for IHs and further explored the mechanisms and targeting drugs, providing a basis for diagnosing and treating IHs.