Gaseous air pollution and acute myocardial infarction mortality in Hong Kong: Atime-stratified case-crossover study

Acute myocardial infarction (AMI) is a common disease with serious consequences in mortality and morbidity. An association between gaseous air pollution and AMI has been suggested, but the epidemiological evidence is still limited. For the study period 1998-2010, daily counts of AMI deaths were collected, as well as daily air pollution data including concentrations of particulates (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3) and carbon monoxide (CO) were also obtained. The associations between gaseous air pollutants and AMI mortality were estimated using time-stratified case-crossover analyses. NO2 and SO2 were found to be significantly associated with increased AMI mortality. The odds ratios (ORs) were 1.0455 (95% confidence interval (CI): 1.017-1.0748) and 1.0256 (95% CI: 1.0027-1.0489) for an interquartile range (IQR) increase in the current day's NO2 and SO2 concentration, respectively, and this association persisted in 2-pollutant models; and no association was observed for CO and O3. It is likely that exposure to elevated ambient NO2 and SO2 air pollution contributed to increased AMI mortality. © 2012 Elsevier Ltd.link_to_subscribed_fulltex

Vitamin D3 supplementation improves testicular function in diabetic rats through peroxisome proliferator‐activated receptor‐γ/transforming growth factor‐beta 1/nuclear factor‐kappa B

Abstract Aims/Introduction Vitamin D3 deficiency can lead to male hypogonadism in diabetes mellitus, but the target organs and the mechanism driving the disorder are unclear. This experiment was designed to study the relationship between vitamin D3 deficiency and hypogonadism in diabetes mellitus. Materials and Methods Rats with streptozotocin‐induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: blank (no vitamin D3), low (0.025 μg/kg/day), high (0.1 μg/kg/day), high (0.1 μg/kg/day) and with bisphenol A diglycidyl ether (peroxisome proliferator‐activated receptor gamma inhibitor 30 mg/kg/day). They were compared with wild‐type rats. Results After 12 weeks, the vitamin D3 supplements had partially restored testicular pathological changes, as shown by reduced testicular fibrosis related to downregulation transforming growth factor beta 1 and apoptosis related to downregulation of nuclear factor kappa B, but not the pituitary gland. The expression of peroxisome proliferator‐activated receptor gamma, which can inhibit transforming growth factor beta 1 and nuclear factor kappa B, was significantly increased after treatment with vitamin D3. Conclusions These results suggest that treatment with vitamin D3 can improve testicular function in diabetic rats through the peroxisome proliferator‐activated receptor gamma/transforming growth factor beta 1/nuclear factor kappa B signaling pathway

Changes in the Small RNA Expression in Endothelial Cells in Response to Inflammatory Stimulation

Objective. Endothelial cell inflammation is a common pathophysiological process in many cardiovascular and cerebrovascular diseases. Small RNA is a kind of short nonprotein coding RNA molecule. Changes in the small RNA expression in endothelial cells have been linked to the development of cardiovascular and cerebrovascular diseases. We investigated and verified differentially expressed small RNAs in endothelial cells in response to inflammatory stimulation. Methods. Primary rat endothelial cells were obtained from Sprague-Dawley rats and treated with 10 ng/ml TNF-α for 24 hours. Small RNA sequencing was used to generate extensive small RNA data. Significantly differentially expressed small RNAs identified in the analysis were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we investigated the tissue-specific small RNA expression after RNA extraction from different tissues. Results. Small RNA sequencing demonstrated that 17 miRNAs, 1 piRNA, 10 snoRNAs, and 7 snRNAs were significantly differentially expressed. qRT-PCR identified 3 miRNAs, 2 snoRNAs, and 2 snRNAs with significantly different expression. Analysis of the tissue-specific expression showed that rno-miR-126a-5p was predominantly expressed in the lung, rno-miR-146a-5p in the intestines, and rno-novel-178 in the heart. Rno-piR-017330 was mainly expressed in the muscle. snoR-8966.1 was predominantly expressed in the bone. snoR-6253.1 was mostly expressed in the vessels and bone. snR-29469.1 was mainly expressed in the bone, and snR-85806.1 was predominantly expressed in the vessels and bone. Conclusions. We report for the first time the expression of small RNAs in endothelial cells under inflammatory conditions. TNF-α can regulate the expression of small RNAs in endothelial cells, and their expression is tissue-specific

Dapagliflozin Attenuates Renal Tubulointerstitial Fibrosis Associated With Type 1 Diabetes by Regulating STAT1/TGF beta 1 Signaling

Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial inhibitory effect of dapagliflozin, a SGLT2 inhibitor, on TIF, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing TIF as well as its possible impact on renal function. TIF in human kidney biopsies obtained from patients with DN was quantified by histopathological staining. In vitro, HK-2 cells were incubated in high glucose with dapagliflozin or fludarabine, and epithelial-mesenchymal transition (EMT) was determined. In vivo experiments were performed in streptozotocin (STZ)-induced type 1 diabetic mice treated with dapagliflozin by gavage for 16 weeks, after which specific functional characteristics and TIF were analyzed. In both DN patients and diabetic mice, fibronectin and Col IV, as well as STAT1 protein in the kidneys were increased as compared with controls. Dapagliflozin significantly decreased blood glucose, and renal STAT1 and TGF-beta 1 expression in mice. Furthermore, dapagliflozin improved renal function, and attenuated diabetes-induced TIE In HK-2 cells, dapagliflozin, and fludarabine directly decreased aberrant STAT1 expression and reversed high glucose-induced downregulation of E-cadherin and a-SMA induction. Thus, the results demonstrate that dapagliflozin not only improves hyperglycemia but also slows down the progression of diabetes-associated renal TIF by improving hyperglycemia-induced activation of the STAT1/TGF-beta 1 pathway

sj-pdf-1-vmj-10.1177_1358863X231218210 – Supplemental material for Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231218210 for Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm by Yan Yan, Xuanfeng Qin, Yongtao Zheng, Tao Jin, Yuanyuan Hu, Qingzhu An and Bing Leng in Vascular Medicine</p

Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

Background/Aims: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. Methods: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. Results: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p&#x3c;0.05). KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. Conclusion: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic mechanical stretch induced smooth muscle cell changes. Smooth muscle cell protection provides an additional therapeutic option to prevent the growth of cerebral aneurysms

Therapeutic Benefit of Bone Marrow–Derived Endothelial Progenitor Cell Transplantation after Experimental Aneurysm Embolization with Coil in Rats

<div><p>Aneurysm embolization with coil is now widely used clinically. However, the recurrence of aneurysms after embolization has always plagued neurosurgeons because the endothelial layer of the aneurysm neck loses its integrity after being embolized by coil. Bone marrow–derived endothelial progenitor cells (BM-EPCs) could be incorporated into injured endothelium and differentiate into mature endothelial cells during vascular repairing processes. The aim of our study is to explore the effects of BM-EPCs on aneurysm repairing and remodeling in a rat embolization model of abdominal aortic aneurysm. BM-EPC proliferation, migration and tube formation were not affected by super-paramagnetic iron oxide nanoparticle (SPIO) labeling compared to the controls (<i>p</i>>0.05). The number of SPIO-labeled cells greatly increased in EPC transplanted rats compared to that of phosphate buffered saline treated rats. SPIO-labeled EPC (SPIO-EPC) are mainly located in the aneurysm neck and surrounded by fibrous tissue. A histology study showed that the aneurysm orifice was closed with neointima and the aneurysm was filled with newly formed fibrous tissue. The SPIO-EPC accumulated in the aneurysm neck, which accelerated focal fibrous tissue remodeling, suggesting that BM-EPCs play a crucial role in repairing and remodeling the aneurysm neck orifice.</p></div

The result of the luminal endothelial layer and the neck tissue HE staining in BM-EPC and control groups.

<p>↑↑ =  increase, ↑ = miner increase and (-) =  no change.</p

Embolization aneurysm specimen handling process.

<p>(<b>a</b>) specimens obtained after cell transplantation for about 6 weeks (<b>b</b>) tissues were sectioned using an isomet low speed saw at 1000 µm intervals in a coronal orientation after being dehydrated and embedded (<b>c</b>), the tissue slices contained a large amount of coils under the microscope (<b>d</b>), the coils were extracted carefully by micro-tweezers under the microscope (<b>e</b>), after coil extraction and re-embedding, the tissue sections were processed into 5 mm slices by a microtome.</p