Temporomandibular Joint Disorders in Patients with Rheumatoid Arthritis

BackgroundTemporomandibular joint disorders (TMD) are not uncommon in patients with rheumatoid arthritis (RA). However, the extent of involvement and its clinical relevance have not been well characterized. This study evaluated the correlation between the severity of RA-related TMD and RA, as well as determined the potential predictors for early identification and management of TMD in RA patients.MethodsWe sequentially recruited 56 adult RA patients from our Arthritis Clinic. TMD and RA were surveyed, clinically by questionnaires and physical examinations, and radiologically by tomography in TMD and conventional radiography in RA. The patients were stratified into no, mild and severe TMD groups according to the physical and tomographic examinations. The correlation of the severity of TMD and RA were evaluated. The relative importance of relevant predictors of severe TMD was analyzed by a logistic regression model.ResultsPhysical and radiologic temporomandibular joint abnormalities were found to be highly prevalent (85.7% and 74.5%) in these patients, and the occurrence increased to as much as 92.9% when the 2 data sets were combined. More than half of the patients had severe TMD presenting with debilitating symptoms or with a significant degree of bony destruction. The severity of TMD was variably correlated with RA severity. The score of hand-joint space narrowing was found to be the most influential predictor of severe TMD by logistic regression analysis.ConclusionThere was a high prevalence of TMD in RA patients. The severity of TMD variably correlated with RA severity. Clinically, a high score of hand-joint space narrowing may serve as an early indicator of RA patients at risk of severe TMD. This may facilitate early management and prevent the functional impairment of the temporomandibular joint

Matrix metalloproteinase-3 promoter polymorphisms but not dupA-H. pylori correlate to duodenal ulcers in H. pylori-infected females

<p>Abstract</p> <p>Background</p> <p>This study investigated if the <it>H. pylori dupA </it>genotype and certain host single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of <it>H. pylori-</it>infected Taiwanese patients.</p> <p>Results</p> <p>Of the 549 <it>H. pylori-</it>infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer) received SNPs analysis of MMP-3_{-1612 6A > 5A}, MMP-7_{-181 A > G}, MMP-9_{exon 6 A > G}, TIMP-1_{372 T > C}and TIMP-2_{-418 G > C}by PCR-RFLP. The 181 collected <it>H. pylori </it>isolates were detected for the <it>dupA </it>genotype by PCR. The rates of <it>dupA</it>-positive <it>H. pylori </it>infection were similar among patients with duodenal ulcer (22.8%), gastric ulcer (20.0%), and gastritis (25.5%) (<it>p </it>> 0.05). Males had higher rates of duodenal ulcer and gastric ulcer than females (<it>p </it>< 0.01). Of <it>H. pylori</it>-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% <it>vs</it>. 74.9%, <it>p </it>< 0.05) in females. This genotype had a 2.4-fold (95% CI: 1.02-5.66) increased risk of duodenal ulcer, compared to those with the 5A carrier. Combining the MMP-3/TIMP-1 genotype as 6A6A/CC, the risk of duodenal ulcer increased up to 3.6 fold (<it>p </it>< 0.05) in <it>H. pylori-</it>infected females.</p> <p>Conclusions</p> <p>The MMP-3 promoter polymorphism, but not the <it>dupA</it>-status, may correlate with susceptibility to duodenal ulcer after <it>H. pylori </it>infection in Taiwanese females.</p

Device Integrity of Drug-eluting Depot Stent for Smart Drug Delivery

Atherosclerosis, or hardening of the arteries, is a condition in which plaque, made of cholesterol, fatty substances, cellular waste products, calcium, and fibrin, builds up inside the arteries. A metallic stent is a small mesh tube that is used to treat these narrowed arteries such as coronary artery diseases. The drug-eluting stent has a metallic stent platform coated with drug-polymer mix and has been shown to be superior to its metallic stent counterpart in reducing restenosis. In the past few years, a novel variation of the drug-eluting stent with micro-sized drug reservoirs (depot stent) has been introduced to the market. It allows smart programmable drug delivery with spatial/temporal control and has potential advantages over conventional stents. The drug-polymer mix compound can be altered from one reservoir to the next, allowing a highly-controlled release of different medications. For example, this depot stent concept can be applied in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) simultaneously. However, the creation of such drug reservoirs on the stent struts inevitably compromises its mechanical integrity. In this study, the effects of these drug reservoirs on stent key clinical attributes were systematically investigated. We developed finite element models to predict the mechanical integrity of a balloon-expandable stent at various stages of its function life such as manufacturing and acute deployment, as well as the stent radial strength and chronic fatigue life. Simulation results show that (1) creating drug reservoirs on a stent strut could impact the stent fatigue resistance to certain degrees; (2) drug reservoirs on the high stress concentration regions led to much greater loss in all key clinical attributes than reservoirs on other locations; (3) reservoir shape change resulted in little differences in all key clinical attributes; and (4) for the same drug loading capacity, larger and fewer reservoirs yielded higher fatigue safety factor. These results can help future stent designers to achieve the optimal balance of stent mechanical integrity and smart drug delivery, thereby opening up a wide variety of new opportunities for disease treatments. We also proposed an optimized depot stent with tripled drug capacity and acceptable marginal trade-off in key clinical attributes when compared to the current drug-eluting stents. This depot stent prototype was manufactured for the demonstration of our design concept

Reciprocal regulation of MicroRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells

BACKGROUND: MicroRNAs (miRNAs), small noncoding RNA molecules can function as oncogenes or tumor suppressors in tumorigenesis. Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with a 5-year survival rate of approximately 50%. METHODS: The expression of microRNA-99a (miR-99a) in OSCC tissues and cell lines was investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. The functions of miR-99a in migration/invasion and lung colonization were determined by transwell and tail vein injection assays, respectively. Specific targets of miR-99a were determined by software prediction, correlation with target protein expression, and luciferase reporter assay. The signaling pathways involved in regulation of miR-99a were investigated using the kinase inhibitors. RESULTS: We observed reduced levels of miR-99a, identified as one of the most downregulated miRNA in OSCC and all tested OSCC cell lines compared to normal oral keratinocytes. Ectopic miR-99a expression in OSCC cells markedly reduced migration and invasion in vitro as well as lung colonization in vivo. When evaluating the specific targets of miR-99a, we found that ectopic miR-99a expression downregulates insulin-like growth factor 1 receptor (IGF1R) protein and that the expression of miR-99a correlates negatively with IGF1R protein in OSCC cells. Insertion of the 3′UTR of IGF1R mRNA into the 3′UTR of a reporter gene markedly reduced luciferase activity in OSCC cells expressing miR-99a, suggesting that miR-99a reduces luciferase activity by targeting the 3′UTR of IGF1R mRNA. When evaluating the mechanisms of miR-99a downregulation, we observed the upregulation of miR-99a expression in serum-starved conditions and its suppression in response to insulin-like growth factor (IGF1) stimulation. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) kinase inhibited IGF1-induced suppression of miR-99a, suggesting the negative regulation of miR-99a expression by IGF1R signaling. CONCLUSION: Overall, results indicate that miR-99a functions as a tumor metastasis suppressor in OSCC cells and mutually regulates IGF1R expression in a reciprocal regulation

The Arabidopsis Malectin-Like/LRR-RLK IOS1 is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity

Plasma membrane-localized pattern recognition receptors (PRRs) such as FLAGELLIN SENSING2 (FLS2), EF-TU RECEPTOR (EFR) and CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) recognize microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). A reverse genetics approach on genes responsive to the priming agent beta-aminobutyric acid (BABA) revealed IMPAIRED OOMYCETE SUSCEPTIBILITY1 (IOS1) as a critical PTI player. Arabidopsis thaliana ios1 mutants were hyper-susceptible to Pseudomonas syringae bacteria. Accordingly, ios1 mutants showed defective PTI responses, notably delayed up-regulation of the PTI-marker gene FLG22-INDUCED RECEPTOR-LIKE KINASE1 (FRK1), reduced callose deposition and mitogen-activated protein kinase activation upon MAMP treatment. Moreover, Arabidopsis lines over-expressing IOS1 were more resistant to bacteria and showed a primed PTI response. In vitro pull-down, bimolecular fluorescence complementation, co-immunoprecipitation, and mass spectrometry analyses supported the existence of complexes between the membrane-localized IOS1 and BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)-dependent PRRs FLS2 and EFR, as well as with the BAK1-independent PRR CERK1. IOS1 also associated with BAK1 in a ligand-independent manner, and positively regulated FLS2-BAK1 complex formation upon MAMP treatment. In addition, IOS1 was critical for chitin-mediated PTI. Finally, ios1 mutants were defective in BABA-induced resistance and priming. This work reveals IOS1 as a novel regulatory protein of FLS2-, EFR- and CERK1-mediated signaling pathways that primes PTI activation

AGE-BSA down-regulates endothelial connexin43 gap junctions

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.</p> <p>Results</p> <p>In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.</p> <p>Conclusions</p> <p>AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.</p