Biosynthesis of Au NPs over modified Fe3O4 support using Rubia Tinctorum extract for the treatment of colorectal carcinoma in the in vitro condition: A pre-clinical trial study

Abstract Purpose Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. “RIC in COVID-19” is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. Methods A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. Conclusions The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. Trial Registration NCT04699227, registered January 7th, 2021.

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Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽

10.1186/s13063-021-05033-x ◽

2021 ◽

Vol 22 (1) ◽

Cited By ~ 1

Author(s):

Iwein Gyselinck ◽

◽

Laurens Liesenborghs ◽

Ewout Landeloos ◽

Ann Belmans ◽

...

Keyword(s):

Clinical Trial ◽

Standard Of Care ◽

Ordinal Scale ◽

Cytokine Signaling ◽

Nasopharyngeal Swab ◽

The Novel ◽

Proof Of Concept ◽

Open Label ◽

Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

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Soluble Epoxide Hydrolase as an Important Player in Intestinal Cell Differentiation

Cells Tissues Organs ◽

10.1159/000512807 ◽

2020 ◽

Vol 209 (4-6) ◽

pp. 177-188

Author(s):

Katerina Cizkova ◽

Katerina Koubova ◽

Tereza Foltynkova ◽

Jana Jiravova ◽

Zdenek Tauber

Keyword(s):

Cell Differentiation ◽

Colorectal Carcinoma ◽

Cell Lines ◽

Epoxide Hydrolase ◽

Soluble Epoxide Hydrolase ◽

Intestinal Cell ◽

Caco2 Cells ◽

Important Player ◽

Ht 29

There is growing evidence that soluble epoxide hydrolase (sEH) may play a role in cell differentiation. sEH metabolizes biologically highly active and generally cytoprotective epoxyeicosatrienoic acids (EETs), generated from arachidonic acid metabolism by CYP epoxygenases (CYP2C and CYP2J subfamilies), to less active corresponding diols. We investigated the effect of sEH inhibitor (TPPU) on the expression of villin, CYP2C8, CYP2C9, CYP2J2, and sEH in undifferentiated and in vitro differentiated HT-29 and Caco2 cell lines. The administration of 10 μM TPPU on differentiated HT-29 and Caco2 cells resulted in a significant decrease in expression of villin, a marker for intestinal cell differentiation. It was accompanied by a disruption of the brush border when microvilli appeared sparse and short in atomic force microscope scans of HT-29 cells. Although inhibition of sEH in differentiated HT-29 and Caco2 cells led to an increase in sEH expression in both cell lines, this treatment had an opposite effect on CYP2J2 expression in HT-29 and Caco2 cells. In addition, tissue samples of colorectal carcinoma and adjacent normal tissues from 45 patients were immunostained for sEH and villin. We detected a significant decrease in the expression of both proteins in colorectal carcinoma in comparison to adjacent normal tissue, and the decrease in both sEH and villin expression revealed a moderate positive association. Taken together, our results showed that sEH is an important player in intestinal cell differentiation.

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Creatine Supplementation for Patients with Inflammatory Bowl Diseases: A Scientific Rationale for a Clinical Trial

Nutrients ◽

10.3390/nu13051429 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1429

Author(s):

Theo Wallimann ◽

Caroline H. T. Hall ◽

Sean P. Colgan ◽

Louise E. Glover

Keyword(s):

Ulcerative Colitis ◽

Clinical Trial ◽

Crohn’S Disease ◽

Pilot Study ◽

Crohn's Disease ◽

Single Case ◽

Initial Period ◽

Creatine Supplementation

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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New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

Molecules ◽

10.3390/molecules26040867 ◽

2021 ◽

Vol 26 (4) ◽

pp. 867

Author(s):

Bruno Oyallon ◽

Marie Brachet-Botineau ◽

Cédric Logé ◽

Thomas Robert ◽

Stéphane Bach ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Cancer Progression ◽

Kinase Inhibitors ◽

Integration Site ◽

Leukemia Virus ◽

Biological Evaluation ◽

Design Synthesis ◽

Proviral Integration Site ◽

Quinoxaline Derivatives

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.

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In Vitro Pharmaco-Toxicological Characterization of Melissa officinalis Total Extract Using Oral, Pharynx and Colorectal Carcinoma Cell Lines

Processes ◽

10.3390/pr9050850 ◽

2021 ◽

Vol 9 (5) ◽

pp. 850

Author(s):

Kristine Guran ◽

Roxana Buzatu ◽

Iulia Pinzaru ◽

Madalina Boruga ◽

Iasmina Marcovici ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Melissa Officinalis ◽

Pharmacological Profile ◽

In Ovo ◽

Total Extract ◽

Antiangiogenic Effect ◽

Beneficial Effects ◽

Gram Positive Bacteria ◽

Potential Benefits

Melissa officinalis is a medicinal herb with an extensive pharmacological profile that has been proven to have beneficial effects in oral and gastrointestinal disorders. However, the effects of this plant in oral, pharyngeal, and colorectal malignancies, types of cancer with an increased incidence in recent years, are less investigated. The present study aims to evaluate the pharmacological profile of a Melissa officinalis total extract for potential benefits in oral, pharynx and colorectal carcinoma. The LC-MS profile of MO total extract (MOte) indicated a rich content in polyphenols, data that support the potent antioxidant capacity exhibited and the antimicrobial activity against both Gram-negative and Gram-positive bacteria. In addition, MOte triggered a dose-dependent and selective decrease in the viability of tumor cells (tongue and pharynx squamous cell carcinomas, and colorectal adenocarcinoma), with the most significant effect being recorded at 100 µg/mL. At the same concentration, MOte exhibited an antiangiogenic effect by inhibiting the process of angiogenesis in ovo. Overall, our findings support the potential benefits of Melissa officinalis leaf total extract as a valuable candidate for the prophylaxis of oral, pharyngeal and colorectal neoplasms.

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