Activatable fluorogenic probe for accurate imaging ulcerative colitis hypoxia in vivo

Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease.

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Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

Frontiers in Chemistry ◽

10.3389/fchem.2021.713078 ◽

2021 ◽

Vol 9 ◽

Author(s):

Thanh Chung Pham ◽

Van-Nghia Nguyen ◽

Yeonghwan Choi ◽

Dongwon Kim ◽

Ok-Sang Jung ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Stokes Shift ◽

Fluorescence Emission ◽

Antibacterial Activities ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

Fluorogenic Probe ◽

High Fluorescence

The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

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A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01064-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lin Chen ◽

Yan Lin ◽

Zijun Zhang ◽

Ruisheng Yang ◽

Xiaosheng Bai ◽

...

Keyword(s):

Colorectal Cancer ◽

Ulcerative Colitis ◽

Colon Cancer ◽

Inclusion Complex ◽

Tumor Suppression ◽

Folate Receptor ◽

Significant Inhibition ◽

Aminosalicylic Acid ◽

Anti Inflammatory

Abstract Background There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD. Results It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. Conclusions Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy. Graphical Abstract

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In-vitro cyclosporin sensitivity of proliferating lymphocytes is predictive of in-vivo therapeutic response in ulcerative colitis

Alimentary Pharmacology & Therapeutics ◽

10.1046/j.1365-2036.2001.00977.x ◽

2001 ◽

Vol 15 (5) ◽

pp. 665-668 ◽

Cited By ~ 4

Author(s):

G. McCormack ◽

D. O'Donoghue ◽

A. Baird

Keyword(s):

Ulcerative Colitis ◽

Therapeutic Response

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An Overview of nano delivery systems for targeting RNA interference-based therapy in ulcerative colitis

Current Pharmaceutical Design ◽

10.2174/1381612827666210617120302 ◽

2021 ◽

Vol 27 ◽

Author(s):

Iman Alfagih ◽

Basmah Aldosari ◽

Bushra AlQuadeib ◽

Alanood Almurshedi ◽

Murtaza Tambuwala

Keyword(s):

Ulcerative Colitis ◽

Rna Interference ◽

Protein Expression ◽

Messenger Rna ◽

Delivery Systems ◽

Target Cells ◽

Intracellular Space ◽

Therapeutic Benefits ◽

Negative Effect

: Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease. UC has a negative effect on patients’ quality of life, and it is an important risk factor for the development of colitis-associated cancer. Patients with UC need to take medications for their entire life because no permanent cure is available. Therefore, approaches that target messenger RNA (mRNA) of proinflammatory cytokines or anti-inflammatory cytokines are needed to improve the safety of UC therapy and promote intestinal mucosa recovery. The major challenge facing RNA interference-based therapy is the delivery of RNA molecules to the intracellular space of target cells. Moreover, nonspeciﬁc and systemic protein expression inhibition can result in adverse effects and less therapeutic beneﬁts. Thus, it is important to develop an efficient delivery strategy targeting the cytoplasm of target cells to avoid side effects caused by off-target protein expression inhibition. This review focuses on the most recent advances in the targeted nano delivery systems of siRNAs and mRNA that have shown in vivo efficacy.

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Inhibition of Prostaglandin Breakdown by Sulphasalazine in Vitro and in Vivo in Relation to the Treatment of Ulcerative Colitis

Verhandlungen der Deutschen Gesellschaft für innere Medizin ◽

10.1007/978-3-642-85454-5_35 ◽

1979 ◽

pp. 202-208

Author(s):

P. K. Moore ◽

J. R. S. Hoult ◽

C. N. Berry

Keyword(s):

Ulcerative Colitis

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Narrow-Band Imaging Colonoscopy to Assess Mucosal Angiogenesis in Ulcerative Colitis

Gastroenterology Research and Practice ◽

10.1155/2019/8312624 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Tao Guo ◽

Jia-Ming Qian ◽

Ai-Ming Yang ◽

Yue Li ◽

Wei-Xun Zhou

Keyword(s):

Ulcerative Colitis ◽

Immunohistochemical Staining ◽

Narrow Band ◽

Narrow Band Imaging ◽

Strong Association ◽

Microvascular Density ◽

Vascular Endothelial ◽

Vascular Pattern ◽

Endothelial Growth Factor

Background and Aim. It has been documented that angiogenesis is a largely unstudied component of the pathogenesis of ulcerative colitis (UC). Under narrow-band imaging (NBI) colonoscopy, the mucosal vascular pattern (MVP) can be visualized without the use of dyes. The aim of this study was to assess the grade of mucosal angiogenesis based on the MVP in UC. Methods. A total of 119 colorectal segments taken from 42 patients with UC were observed using NBI colonoscopy. The MVP was classified as follows: clear, obscure, or absent. Quantification of the degree of inflammation was performed using histological colitis scoring. Potent angiogenic activity was assessed by immunohistochemical staining for vascular endothelial growth factor (VEGF). Microvascular density was assessed using vessel counts as revealed by CD31 staining. The correlation between the MVP and histological grades of inflammation and angiogenesis was evaluated. Results. The MVP correlated well with the histological severity of inflammation. We also demonstrated an increasing level of microvascular density and VEGF staining along with the ordered types of MVPs. In addition, a statistically strong association existed between microvascular density and VEGF staining. Conclusions. NBI colonoscopy might be a useful tool for the in vivo assessment of the grade of mucosal angiogenesis in UC.

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Jiaweishaoyao Decoction Alleviates DSS-Induced Ulcerative Colitis via Inhibiting Inflammation

Gastroenterology Research and Practice ◽

10.1155/2020/7182874 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Huixia Qiao ◽

Yahui Huang ◽

Xiaoyan Chen ◽

Long Yang ◽

Yue Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Nlrp3 Inflammasome ◽

Activity Index ◽

Raw264.7 Cells ◽

Spleen Weight ◽

Associated Proteins ◽

Histopathological Score

Purpose. Jiaweishaoyao decoction (JWSYD) is a traditional prescription of Chinese medicine that is initially used for the treatment of diarrhea. This study is aimed at investigating the effects of JWSYD on DSS-induced ulcerative colitis (UC). Methods. DSS-induced UC mice and LPS-induced RAW264.7 cells were used as the UC model in vivo and in vitro. UC was assessed by body weight, disease activity index (DAI), colon length, spleen weight, and histopathological score (HE staining). The levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA and qRT-PCR. The levels of NLRP3 inflammasome- and NF-κB pathway-associated proteins were measured by western blot. Results. JWSYD alleviated DSS-induced UC in respect to body weight, DAI, colon length, spleen weight, and histopathological score. JWSYD reduced the levels of TNF-α, IL-1β, and IL-6 in DSS-induced UC mice and the supernatants of LPS-induced RAW264.7 cells. JWSYD suppressed the protein levels of inflammasome-associated proteins, including NLRP3, ASC1, Procaspase-1, Cleaved caspase-1, and Cleaved IL-1β in DSS-induced UC mice and LPS-induced RAW264.7 cells. In addition, JWSYD suppressed the NF-κB pathway in vitro and in vivo. Conclusion. JWSYD alleviated DSS-induced UC via inhibiting the NLRP3 inflammasome and NF-κB pathway.

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