Effects of oral vitamin D3 supplementation in Crohn's disease patients: Modulation of clinical active/remission phases by pro-inflammatory cytokines profile and oxidative stress

Q4 · MEDICINE

Article

Author: Asselah, Hocine ; Ayoub, Soraya ; Koceir, Elhadj-Ahmed ; Hantala, Djaffar ; Tahar, Amina ; Berriche-Yahi, Naziha

The 25-hydroxyvitamin D₃ (25OHD₃) deficiency in Crohn's disease (CD) is associated with the immune system dysfunction and redox status alteration. These two events affect intestinal mucosal function through macrophages cells infiltration and to lead a pro-inflammatory cytokines storm and ROS (reactive oxygen species) overproduction. The objective of this study was to investigate the immunomodulatory and antioxidant effects of vitamin D₃ supplementation (DS₃) in clinical active phase. A cohort of 262 CD patients and vitamin D deficient (< 50 nmol/L or < 20 ng/mL) was randomized into 2 groups according to the DS₃ doses at 200,000 IU/month (D₂₀₀ group) versus 6,000 IU/day (D₆ group). Serum 25OHD₃ levels were assessed before and after 6 and 12 months of DS₃. The clinical active phase was characterized by the CDAI score (Crohn's Disease Activity Index) and the fecal calprotectin assay. The 25OHD₃ profile was analyzed by LC-MS/MS. The pro-inflammatory cytokines (TNFα, IL-6, IL-12, IL-17, IL-23) were assessed by ELISA tests. The serum trace elements (Se, Mn, Cu, Zn) was determined by mass spectrometry. The antioxidant status (TAS, SOD, GPx, GSH) was evaluated by Randox kits. The results showed that the serum 25OHD₃ concentrations became normal (> 75 nmol/L or > 30 ng/mL) in the 2 groups. Our data showed that vitamin D supplementation allowed the clinical remission phase. The DS3 decreased serum levels of CRPus, TNFα, IL-17 and IL-23. The DS3 modulates the trace elements ratio and increased the SOD and GPx activities. The DS3 corrects the denutrition state. The vitamin D supplementation benefits are more significant in D₆ group (continuous 6,000 IU/day) than in D₂₀₀ group (intermittent 200,000 IU/month). Our study suggests that the serum 25OHD₃ profile can be considered a reliable biomarker in the bioclinic CD evolution to prevent the active phase, to extend the remission phase and to avoid the surgical bowel resection.

02 Jan 2022·Leukemia & Lymphoma

Prognostication of diffuse large B-cell lymphoma patients with Deauville score of 3 or 4 at end-of-treatment PET evaluation: a comparison of the Deauville 5-point scale and the ΔSUVmax method

Letter

Author: Tan, Ya Hwee ; Yang, Valerie S. ; Tao, Miriam ; Lam, Winnie W. ; Chang, Esther W. ; Chan, Jason Y. ; Chiang, Jianbang ; Farid H. Rashid, Mohamed ; Khoo, Lay Poh ; Lim, Soon Thye ; Ng, David Z. ; Tong, Aaron K. ; Lee, Chuan Yaw ; Somasundaram, Nagavalli ; Tan, Sze Huey ; Poon, Eileen Y.

Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI) <3 selects for patients with extremely low risk of disease progression (HR 0.06, 95% CI 0.01 to 0.62, p 0.018) compared to DS 4 and IPI ≥3.

01 Oct 2021·AIDSQ2 · MEDICINE

The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate

Q2 · MEDICINE

Article

Author: Armanasco, Naomi ; Aldon, Yoann ; Shattock, Robin J. ; Ziprin, Paul ; Herrera, Carolina ; Stieh, Daniel ; Nuttall, Jeremy ; Harman, Sarah ; Rogers, Paul

Objective:Small molecule inhibitors able to bind to gp120 and prevent CD4+-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action.Design:Preclinical analysis was performed with human mucosal tissue models as surrogates of in-vivo activity.Methods:Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+ T cells) with several dosing times (2, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4+ (sCD4+) and an anti-CD4+ induced antibody, 17b.Results:In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4+ impeded DS003 binding to viral envelope. In contrast, DS003 did not impact subsequent binding of sCD4+. Furthermore, sCD4+-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003.Conclusion:DS003 inhibits HIV-1 infection by binding to or near the CD4+ binding site of gp120, preventing CD4+-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.

100 Deals associated with DS003(Tashi Pharmaceutical)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	IND Approval	CN	Dashi Pharmaceutical (Guangdong) Co., Ltd.	14 Oct 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

DS003(Tashi Pharmaceutical)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation