Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis.

Myeloid differentiation 1 (MD-1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD-2 and forms a complex with radioprotective 105 (RP105). RP105/MD-1 complex negatively regulates toll-like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD-1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD-1 in IBD, we inhibited MD-1 in colon with antisense oligonucleotide (AS-ODN) and assessed the effect of MD-1 inhibition on dextran sodium sulfate (DSS)-induced colitis. We discovered that MD-1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS-induced colitis. For the first time, we showed that oral administration of MD-1 AS-ODN to mice significantly suppressed the MD-1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD-1 AS-ODN treated mice were more susceptible to DSS-induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD-1 inhibition also significantly enhanced inflammatory cytokines production such as IL-6 and IL-1ß in colons. Finally, mice treated with MD-1 AS-ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)-κB activation compared with the control. Taken together, specifically suppression of MD-1 in colon tissues with AS-ODN exacerbates DSS-induced experimental colitis in mice, which is possibly related to activation of TLR4/NF-κB signaling.

Effects of Ankle Orthoses, Taping, and Insoles on Postural Stability of Individuals with Chronic Ankle Instability: A Systematic Review.

Chronic ankle instability (CAI) is a prevalent condition characterized by recurring instances of the ankle giving way and persistent symptoms, including pain and diminished function. Foot and ankle external supports are commonly used in clinical practice and research for treating CAI. This systematic review aimed to assess the effects of foot and ankle external supports on the postural stability of individuals with CAI to guide clinical practice and inform future research. A comprehensive search was conducted in PubMed, Web of Science, Scopus, and Google Scholar databases from 1 January 2012 to 1 November 2022. Eighteen studies involving individuals with CAI were chosen in this systematic review. The quality of the included studies and risk of bias were assessed using Cochrane Collaboration's tool for randomized controlled trials, the Newcastle-Ottawa Scale for case-control studies, and the DELPHl-list for crossover trial studies. The external supports included in this review were ankle orthoses (elastic, semi-rigid, and active orthoses), taping (kinesiotaping and fibular reposition taping), and insoles (textured and supportive insoles). The outcome measures included static and dynamic postural stability tests, such as the single-leg stance test, star excursion balance test, Y-balance test, single-leg landing test, lateral jump test, walking test, and running test. The results showed that elastic orthoses, Kinesiotaping, and textured insoles demonstrated potential benefits in improving postural stability in individuals with CAI. Elastic orthoses decreased ankle joint motion variability, kinesiotaping facilitated cutaneous receptors and proprioceptive feedback, while textured insoles increased tactile stimulation and foot position awareness. However, the effects of semi-rigid orthoses, fibular reposition taping, and arch support insoles were inconsistent across studies. Future research should explore the long-term effects of these external supports, analyze the effects of different characteristics and combinations of supports, and employ standardized outcome measures and testing protocols for assessing postural stability.