The roles of asparagine-linked glycosylation (ALG) members in tumorigenic process have been widely explored. However, their effects in colorectal cancer progression are still confusing. Here, we screened 12 ALGs' expression through online datasets and found that ALG10 was mostly upregulated in colorectal cancer tissues. We found that ALG10 knockdown significantly suppressed the expression of stemness markers, ALDH activity, and sphere-formation ability. In vivo tumorigenic analysis indicated that ALG10 knockdown attenuated the tumor-initiating ability and chemoresistance of colorectal cancer cells. Further mechanistic studies showed that ALG10 knockdown suppressed the activity of TGF-β signaling by reducing TGFBR2 glycosylation, which was necessary for ALG10-mediated effects on colorectal cancer stemness; Conversely, TGF-β signaling activated ALG10 gene promoter activity through Smad2's binding to ALG10 gene promoter and TGF-β signaling promoted the stemness of colorectal cancer cells in an ALG10-dependent manner. This work identified a novel ALG10/TGF-β positive regulatory loop responsible for colorectal cancer stemness.
Background: Osteoarthritis (OA) often affects the hands, knees, and hip joints, causing considerable pain and disability, and often affecting the patient's quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are common pain relievers often applied as first line therapies for OA. However, prolonged NSAIDs application can have unwanted side effects. Given this, this study was designed to systematically evaluate the efficacy and safety of topical and oral NSAIDs for the treatment of OA.Methods: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant papers from their inception dates to May 2021. Our study only included randomized controlled trials comparing topical and oral NSAIDs and all data were analyzed using Review Manager version 5.3 (RevMan version 5.3).Results: We identified 8 RCTs (2096 patients with OA), for evaluation and revealed that, in general, topical and oral NSAIDs presented with similar efficacies for the treatment of OA. The Western Ontario and McMaster Osteoarthritis Index for assessing pain relief in OA patients was (standardized mean difference [SMD] 0.07; 95%CI −0.02, 0.17) and visual analog scale was (SMD −0.01; 95%CI −0.02, 0.18), and improved stiffness in OA patients (SMD 0.09; 95%Cl 0.03, 0.20).Conclusions: Topical NSAIDs are as effective as oral NSAIDs for the treatment of OA and both topical and oral NSAIDs are equally effective in reducing pain and improving physical function in OA patients. In terms of safety, a larger number of samples are still needed to determine if there are any differences in the safety profile of topical or oral NSAIDs.
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