Changes to tear cytokines of type 2 diabetic patients with or without retinopathy

Purpose: To investigate changes in cytokine levels in tears of type 2 diabetics with or without retinopathy. Methods: Tears were collected from 15 type 2 diabetics without retinopathy (DNR), 15 patients with retinopathy (DR), and 15 age and gender matched non-diabetic controls. Tear concentrations of 27 cytokines were measured by multiplex bead immunoassay. Cytokine differences between groups, ratios of type-1 T helper (Th1)/type-2 T helper (Th2) cytokines and anti-angiogenic/pro-angiogenic cytokines were analyzed statistically. Results: The most abundant cytokine detected in tears was interferon-induced protein-10 (IP-10). In comparison with controls, IP-10 and monocyte chemoattracant protein-1 (MCP-1) levels were significantly elevated in DR (p=0.016 and 0.036, respectively) and DNR groups (p=0.021 and 0.026, respectively). Interleukin-1 (IL-1) receptor antagonist (IL-1ra) levels were significantly increased in DNR (p=0.016). Th1/Th2 cytokines interferon-gamma (IFN-γ)/IL-5 and IL-2/IL-5 ratios were significantly increased in DR compared to controls (p=0.037 and 0.031, respectively). Anti-angiogenic/angiogenic cytokines IFN-γ/MCP-1 and IL-4/MCP-1 ratios in DR and DNR were significantly decreased compared to controls (p<0.05). IL-4/IL-8 and IL-12p70/IL-8 ratios were also significantly decreased in DR compared to controls (p=0.02 and 0.045, respectively). No significant correlation was demonstrated between tear cytokine concentrations and glycosylated hemoglobin (HbA1c) or fasting plasma glucose (FPG). Conclusions: Diabetic tears exhibited elevated levels of IP-10 and MCP-1. The Th1/Th2 cytokine balance may shift to a predominantly Th1 state in DR patients. Pro-angiogenic cytokines are more highly represented than anti-angiogenic cytokines in the tears of diabetic patients.8 page(s

Advanced glycation end product (AGE) modified proteins in tears of diabetic patients

Purpose: High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with nondiabetic controls (CTL). Methods: Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1Dand 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Results: Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Conclusions: Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.9 page(s

Fatty infiltration of the pancreas: a systematic concept analysis

Fatty infiltration of the pancreas (FIP) has been recognized for nearly a century, yet many aspects of this condition remain unclear. Regular literature reviews on the diagnosis, consequences, and management of FIP are crucial. This review article highlights the various disorders for which FIP has been established as a risk factor, including type 2 diabetes mellitus (T2DM), pancreatitis, pancreatic fistula (PF), metabolic syndrome (MS), polycystic ovary syndrome (PCOS), and pancreatic duct adenocarcinoma (PDAC), as well as the new investigation tools. Given the interdisciplinary nature of FIP research, a broad range of healthcare specialists are involved. This review article covers key aspects of FIP, including nomenclature and definition of pancreatic fat infiltration, history and epidemiology, etiology and pathophysiology, clinical presentation and diagnosis, clinical consequences, and treatment. This review is presented in a detailed narrative format for accessibility to clinicians and medical students

Mechanism of FKBP10 promoting proliferation and migration of gastric cancer cells

Objective To investigate the regulative role of FKBP10 in the progression of gastric cancer and the underlying mechanism. Methods Bioinformatics analysis was applied to detect the expression of FKBP10 in gastric cancer samples and normal samples, as well as analyze its relationship with prognosis. qRT-PCR and Western blotting were employed to measure its expression at mRNA and protein levels in gastric cancer cell lines BGC823, MGC803, SGC7901, MKN45 and AGS and human gastric epithelial cell line GES. Then colony formation and transwell assay were conducted to detect the effect of its down-regulation on the proliferation and migration of the cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to reveal the FKBP10 involved signaling pathways, which was verified by Western blotting. Results FKBP10 was up-regulated in gastric cancer cell lines than the GES cells. Knockdown of FKBP10 by siRNA restricted the proliferative and migrative abilities of gastric cancer cells. KEGG analysis indicated that FKBP10 may be involved in the process of epithelial-mesenchymal transition (EMT) and TGF-β played important role in the process. Western blotting showed that down-regulation of FKBP10 resulted in increased expression of epithelial related biomarkers while decreased expression of mesenchymal related biomarkers, then the expression of p-SMAD2/3 were reduced simultaneously. Conclusion FKBP10 promotes the proliferation and migration of gastric cancer via regulating EMT and TGF-β/SMAD signaling pathway

Identification of ferroptosis and drug resistance related hub genes to predict the prognosis in Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Currently, overcoming the drug resistance in HCC is a critical challenge and ferroptosis has emerged as a promising therapeutic option for cancer. We aim to construct a new gene signature related to ferroptosis and drug resistance to predict the prognosis in HCC. The RNA-seq data of HCC patients was obtained from the Cancer Genome Atlas database. Using least absolute shrinkage and selection operator cox regression, Kaplan–Meier analysis, and differential analysis, we constructed a prognostic model consisting of six hub genes (TOP2A, BIRC5, VEGFA, HIF1A, FTH1, ACSL3) related to ferroptosis and drug resistance in HCC. Functional enrichment, pathway enrichment and GSEA analysis were performed to investigate the potential molecular mechanism, and construction of PPI, mRNA-miRNA, mRNA-RBP, mRNA-TF and mRNA-drugs interaction networks to predict its interaction with different molecules. Clinical prognostic characteristics were revealed by univariate, multivariate cox regression analysis and nomogram. We also analyzed the relationship between the signature, immune checkpoints, and drug sensitivity. The expression of the gene signature was detected in HCC cell lines and HPA database. Our prognostic model classified patients into high and low-risk groups based on the risk scores and found the expression level of the genes was higher in the high-risk group than the low-risk group, demonstrating that high expression of the hub genes was associated with poor prognosis in HCC. ROC analysis revealed its high diagnostic efficacy in both HCC and normal tissues. The proportional hazards model and calibration analysis confirmed that the model’s prediction was most accurate for 1- and 3-years survival. QRT-PCR showed the high expression level of the gene signature in HCC. Our study built a novel gene signature with good potential to predict the prognosis of HCC, which may provide new therapeutic targets and molecular mechanism for HCC diagnosis and treatment

Oxidative stress as a bridge between age and stroke: A narrative review

Stroke is the third most common cause of death globally and a leading cause of disability. The cellular and molecular changes following stroke and causes of neuronal death are not fully understood, and there are few effective treatments currently available. A rapid increase in the levels of reactive oxygen species (ROS) post stroke can overwhelm antioxidant defenses and trigger a series of pathophysiologic events including the inflammatory response, blood-brain barrier (BBB) disruption, apoptosis, and autophagy, ultimately leading to neuron degeneration and apoptosis. It is thought that beyond a certain age, the ROS accumulation resulting from stroke increases the risk of morbidity and mortality. In the present review, we summarize the role of oxidative stress (OS) as a link between aging and stroke pathogenesis. We also discuss how antioxidants can play a beneficial role in the prevention and treatment of stroke by eliminating harmful ROS, delaying aging, and alleviating damage to neurons

The Comparison between Endoscopic Submucosal Dissection and Surgery in Gastric Cancer: A Systematic Review and Meta-Analysis

Aims. There are two treatment modalities for early gastric cancer (EGC)—surgery and endoscopic submucosal dissection (ESD). We aimed to compare the safety and efficacy of ESD with surgery. Method. The article was performed by searching PubMed databases. Data were extracted using predefined form and odds ratios (OR) with 95% confidence intervals (CI) calculated and P value. Results. 13 studies were identified. The incidence of perforation in two groups was different [OR = 6.18 (95% CI: 1.37–27.98), P=0.02]. The prevalences of synchronous and metachronous cancer in the ESD group were higher than those in the surgery group [OR = 8.52 (95% CI: 1.99–36.56), P = 0.004 and OR = 7.15 (95% CI: 2.95–17.32), P<0.0001]. The recurrence and complete resection rates were different [OR = 6.93 (95% CI: 2.83–16.96), P<0.0001 and OR = 0.32 (95% CI: 0.20–0.52), P<0.00001]. Compared with the surgery group, the hospital stay was shorter [IV = −7.15 (95% CI: −9.08–5.22), P<0.00001], the adverse event rate was lower, and the quality of life (QOL) was better in the ESD group. The difference of bleeding was not found. Conclusion. ESD appears to be preferable for EGC, due to a lower rate of adverse events, shorter hospital stay, cheaper cost, and higher QOL