Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by episodes relative of oral and / or genital ulcers, as well as cutaneous lesions. The participation of the occult, vascular, gastrointestinal neurological system can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones of the management of the BS. Biological agents have been recommended for serious and / or refractory BS. Interferon-α (IFN-α) had several biological effects, such as antiviral and antiproliferative, which can regulate innate and adaptive immunity in BS. The growing evidence has shown the effectiveness of IFN-α in severe and / or refractory BS. Numerous studies have shown that IFN-α has comparable efficiency and tolerance profiles as anti-tumorized necrosis (TNF) factor agents for BehCet uveitis with much lower cost effects. and steroid and immunosuppressor.
IFN-α has been recommended as second-line processing for Ocular participation of BS in Eula (the European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions at BS with the dose of 3 to 9-12 Millions of IU three times a week. Some cases indicated the therapeutic potential of IFN-α in intestinal Bs. As a new IFN-α test in vascular BS (VBS), a recent study revealed the lower relapse rate and the higher reconditionalization rate with the thrombosis of the deep vein of the lower limbs (DVT). Two other case reports presented the effectiveness of IFN-α in the participation of the pulmonary artery in BS. In addition, case reports have shown successful treatment in refractory neurological participation.
There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2B. IFN-α2A seemed more effective than IFN-α2B, particularly in the ocular and mucous participation of BS. The side effects of IFN-α are dependent on dose and non-serious. The most common side effects are flu syndrome, soft leukopenia and alopecia. Given the potential risk of tuberculosis (TB) and hepatitis B (HBV) reactivation of TNF-α inhibitors, IFN-α is safe because of its anti-VHB effect and effect. protection on tuberculosis. In conclusion, IFN-α is a promising choice for severe and / or refractory BS patients, particularly for those who are intolerant or opposable to other biological agents, such as TNF inhibitors. Other prospective controlled studies are justified to confirm the effectiveness and safety of IFN-α in BS.
Type I Interferon (IFN) – Geographic activation of canonical and non-canonic signaling pathways
For several decades, the accumulation of evidence has involved involving type I interferons (IFNS) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type IFN type proteins have been used successfully to treat a diverse group of diseases with significant and positive results. The biological activities of Type I IFNs are consequences of signaling events occurring in the cytoplasm and cell core.
The biochemical events involving JAK / STAT proteins that control the activation of the transcription of the genes stimulated by the IFN (ISG) were the first to be identified and are called “canonical” signaling. The subsequent identification of JAK / statistics independent signaling routes, critical for translating ISG and / or mRNA transcription, are noted “non-canonical” or “non-classical” channels. In this review, we summarize these signaling cascades and discuss recent developments in the field, particularly with regard to the biological and clinical implications of the engagement of canonical and non-canonical channels.
[Progress in interferon: A treatment of Behcet syndrome]
Justification for Covid-19 treatment with nebulized interferon-β-1B-review of the literature and a personal preliminary experience
The inflammatory response to Covid-19 is specifically associated with a type I interferon response type I (IFN) and a complete comprehensive blockade of IFN-β secretion. Clinically, the nebulization of IFN-α-2B has been historically used in China to treat viral pneumonia associated with SARS-VOCs. Very recent data show that the use of an inhaled type I IFN is associated with a decrease in mortality in Chinese patients Covid-19. However, the nebulization of IFN is currently not standard in Europe and the United States. As a result, our group has put in place a project to assess the possibility of nebulizing IFN-β-1b (a drug currently used in Europe to treat multiple multiple sclerosis via subcutaneous injections) and to evaluate
The safety of this new mode of administration in COV-2 infected patients. We present here data from the literature that have allowed us to build our hypothesis and develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to obtain a first pre-clinical and clinical experience of IFN- nebulization. β-1b. After the validation of the nebulization method and the verification of the drop size compatible with the nebulization, the method has been applied to four intensive care patients treated at our university hospital, for which none of the civid-19 therapies initially used in France has led to an important clinical improvement. All patients showed a negative viral car and experienced clinical improvement 7-16 days after initiating the nebulized inhalation therapy of IFN-β-1B. No side effects have been observed. All patients were alive in a 90-day follow-up.
Description: Many solid tumors contain heterogeneous populations of normal and cancerous cells. Separation of these cell populations is key to an accurate assessment of the true genotypic and phenotypic differences between normal and tumor cells. Our CytoSelect Clonogenic Tumor Cell Isolation Kit uses a proprietary semisolid agar medium to facilitate formation of colonies by cells from solid tumors. Colonies are grown in either a 6-well plate or a 35mm culture dish. These colonies are isolated away from single (i.e. normal) cells by size filtration. The viable cells from these colonies can be easily recovered for further analysis.
Tissue cDNA, First Strand, Human Tumor Cell Line, Jurkat (Human Acute T cell Leukemia), BioGenomics
Description: Many solid tumors contain heterogeneous populations of normal and cancerous cells. Separation of these cell populations is key to an accurate assessment of the true genotypic and phenotypic differences between normal and tumor cells. Our CytoSelect Clonogenic Tumor Cell Isolation Kit uses a proprietary semisolid agar medium to facilitate formation of colonies by cells from solid tumors. Colonies are grown in either a 6-well plate or a 35mm culture dish. These colonies are isolated away from single (i.e. normal) cells by size filtration. The viable cells from these colonies can be easily recovered for further analysis.
Tissue cDNA, First Strand, Human Tumor Cell Line, A431 (Human Epidermoid Carcinoma), BioGenomics
Description: Leukocyte or tumor cell interactions with vascular endothelium consist of a cascade of processes including the firm attachment of cells to endothelial cell adhesion molecules. The CytoSelect Tumor Endothelium Adhesion Assay provides a robust system for the quantitative determination of interactions between tumor cells and endothelium. Adherent cells can be easily quantified on a fluorescence plate reader.
Tissue, Total Protein, Human Tumor Cell Line, Jurkat (Human Acute T cell Leukemia)
Description: This cell lysate is prepared from human mcf-7 using Boster's RIPA Lysis Buffer (AR0105) using a standard whole cell lysate protocol. The concentration was determined using the BCA assay process and then diluted using Dithiothreitol (DTT) and a reducing SDS sample loading buffer, heated for 5 minutes at 100˚C.
Description: Traditionally, the soft agar colony formation assay has been used to monitor anchorage-independent growth. Cells proliferate for 3-4 weeks in a semisolid culture medium, followed by tedious manual counting of colonies. Our CytoSelect 96-Well In Vitro Tumor Sensitivity Assay provides a stringent, anchorage-independent model for chemosenstivity testing and screening of potential anticancer drugs. After just 6-8 days, cell colonies are quantified using a standard colorimetric microplate reader.
Description: Human PRKDC (-/-); PRKDC cDNA overexpression HCT116 Cell line is Homozygous knockdown of endogenous PRKDC with overexpression of wild type PRKDC
Human NHEJ1 (-/-); NHEJ1 cDNA overexpression HCT116 Cell Line
Description: Human PRKDC (-/-); PRKDC cDNA overexpression HCT116 Cell line is Homozygous knockout of endogenous PRKDC with overexpression of wild type PRKDC
MCF2L2 (untagged)-Human MCF.2 cell line derived transforming sequence-like 2 (MCF2L2)
Although it is not possible to draw firm conclusions on the effectiveness of the processing based on this case report, our study shows that IFN-β-1b pulmonary administration is feasible, with a good safety profile. This procedure, which has the advantage of directly targeting lungs and reducing the risks of systemic side effects, can represent a promising therapeutic strategy for supporting patients with severe Covid-19. However, our preliminary observation requires confirmation through randomized controlled trials.
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