Bidirectional association between infectious gastroenteritis and inflammatory bowel disease: a population-based study.

BACKGROUND: Intertwined association between infectious gastroenteritis (IGE) and inflammatory bowel disease (IBD) has not been investigated clearly. We aimed to examine the bidirectional association between IGE and IBD. METHODS: A bidirectional study using the Taiwan National Health Insurance Research Database was designed. Through a case-control design, we identified 2899 new IBD cases during 2006-2017 and matched to 28,990 non-IBD controls. We used conditional logistic regression model to estimate odds ratios (OR) of IBD for previous IGE in different exposure time-windows within 5-years before IBD diagnosis and Poisson regression model to estimate incidence rate ratio (IRR) of subsequent IGE for IBD group to non-IBD group. RESULTS: The mean age at the initial IBD diagnosis was 41 years. More IBD patients (21.49%) than controls (12.60%) had been exposed to IGE during > 6 months to 5 years before IBD diagnosis, the OR of IBD for IGE was 1.89 [95% confidence interval: 1.69-2.11]. Excess OR decreased as IGE exposure time before the index date increased. More IGE episodes were associated with additional increase in IBD risk (OR: 1.64, 2.19, 2.57, 3.50, and 4.57 in patients with 1, 2, 3, 4, and ≥ 5 IGE episodes, respectively). The IRR of having IGE for IBD group to non-IBD group was 2.42 before IBD diagnosis and increased to 5.74 after IBD diagnosis. CONCLUSIONS: These findings suggested an IGE-IBD bidirectional association. More attention is needed for physicians to develop preventive strategies and be aware of the higher risk of subsequent IGE in IBD patients.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis.

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia, but the mechanism underlying this relationship is unclear. In this study, we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stroke. miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion, as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits. In a PC12 cell oxygen-glucose deprivation/reoxygenation model, a miR-324-3p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis, whereas treatment with a miR-324-3p inhibitor had the opposite effects. Silencing miR-324-3p increased adenosine A1 receptor (A1R) expression through regulation of GATA binding protein 2 (GATA2). These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Dex-Aco coating simultaneously increase the biocompatibility and transfection efficiency of cationic polymeric gene vectors.

Cationic polymeric vectors attracted plenty of attentions in gene therapy due to nonimmunogenicity, easy to synthesis and flexible properties. However, biocompatibility challenge such as nonspecific interactions with blood cells and serum proteins, may affect the delivery efficiency of cationic vectors; besides, inefficient endosomal escape causes low transfection efficiency. Herein, we synthesized an anionic coating polymer dextran-g-aconic anhydride (Dex-Aco, DA) through a simple esterification reaction, which can protect cationic polymer poly(cystamine-bis-acrylamide)-agmatine-histamine (PCAH, PC) constructed nanomedicine against interactions with blood cells and serum proteins, improving biocompatibility. Interestingly, DA coating significantly increased the transfection efficiency of cationic PC，not due to the increase of cellular uptake, nor functioning as a receptor ligand, but was associated to the change of endocytosis pathway. Finally, using programmed cell death protein 4 (PDCD4) as a functional gene, DA coating PC NPs showed improved therapeutic effect and biocompatibility on tumor bearing mice. We believe that this DA coating PC NPs provides a facile method to improve the performance of cationic polymer vectors in gene therapy and has great potential for clinical applications.

Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis.

Finding a cure for breast cancer currently remains a medical challenge in due to the failure of common treatment methods to inhibit invasion and metastasis of cancer cells, which eventually leads to recurrence of breast cancer. Many secreted proteins are overexpressed and play crucial roles in tumorigenesis and development. The Golgi apparatus is a key protein processing and secretion factory in which metastasis-associated proteins are modified, transported and secreted; thus, regulating the Golgi apparatus of tumor cells is a viable strategy to inhibit tumor metastasis. Herein, celecoxib (CLX) and Brefeldin A (BFA) were encapsulated into the biocompatible polymer PLGA-PEG to form nanoparticles that act on the Golgi apparatus to treat metastatic breast cancer; CLX is a specific COX-2 inhibitor which accumulates in the Golgi apparatus, and BFA is a protein transport inhibitor fusing the Golgi apparatus into endoplasmic reticulum. The optimized CLX and BFA co-loaded nanoparticles (CBNPs) possessed good physicochemical properties. CBNPs efficiently damaged the Golgi apparatus within 30 min and showed enhanced cytotoxicity of CLX and BFA toward murine metastatic breast cancer 4T1 cells. The migration and invasion abilities of the cells were dramatically suppressed by the CBNPs. Further, the expression and secretion of metastasis-associated proteins such as matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) were remarkably decreased. Our findings showed that co-delivering CLX and BFA to regulate the Golgi apparatus may be an efficient strategy to inhibit breast cancer growth and suppress tumor cell metastasis.

A new strategy for hydrophobic drug delivery using a hydrophilic polymer equipped with stacking units.

A highly hydrophilic polymer equipped with guanidinium groups was used to load aromatic ring-containing hydrophobic agent doxorubicin (DOX) via π-π interaction. The results have shown that the delivery system exhibited enhanced cellular uptake and antitumor efficiency compared with free drugs. This study opens new avenues for the application of hydrophilic polymers in drug delivery.