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Systemic delivery of siRNA to the colon using peptide modified PEG-PCL polymer micelles for the treatment of ulcerative colitis
In this study, we investigated the effects of siRNA delivered using MPEG-PCL-CH2R4H2C nanomicelles through intravenous administration to the inflammation site of dextran sulfate sodium-induced colitis mice. The MPEG-PCL-CH2R4H2C micelles had optimum physical properties and high siRNA compaction ability. Moreover, model-siRNA delivered through MPEG-PCL-CH2R4H2C showed higher accumulation in the inflammatory site than that of the naked siRNA. Furthermore, intravenous administration of MPEG-PCL-CH2R4H2C/siRelA micelles, targeting siRelA, a subunit of NF-κB, significantly decreased the shortening of large intestine, clinical ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - December 29, 2021 Category: Drugs & Pharmacology Authors: Hisako Ibaraki Naruhiro Hatakeyama Naoki Arima Akihiro Takeda Yasuo Seta Takanori Kanazawa Source Type: research

Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway
This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as in vitro and in vivo models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects o...
Source: Frontiers in Pharmacology - April 13, 2021 Category: Drugs & Pharmacology Source Type: research

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research