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Background: Chronic urticaria is a long-lasting condition, sometimes with serious comorbidities, severely affecting the quality of life, which makes the patients seek efficient therapies to achieve sustained remissions. The complex nature of urticaria greatly complicates the patients’ responses to appropriate treatments. Objectives: This review was conducted to focus on the Janus kinase (JAK) pathway, evaluate its role as a new biomarker, and discover the efficacy of its inhibitors as novel therapeutic agents in the treatment of refractory chronic urticaria. Methods: Electronic databases of PubMed and SCOPUS were searched to find and evaluate all the reports describing “Janus kinase,” “JAK-STAT pathway,” “chronic urticaria,” “JAK inhibitors,” and “pruritus.” Because itching is the most annoying symptom of chronic urticaria and due to the scarcity of articles conducted on the use of JAK inhibitors in the treatment of this disease, we also reviewed quite a few articles performed on applying JAK inhibitors in the treatment of dermatologic disorders and also pruritus in atopic dermatitis. Results: From the initially retrieved articles, only five were exclusively about the use of JAK inhibitors in the treatment of chronic urticaria. Conclusions: Although JAK inhibitors are widely known as effective therapies in the treatment of some dermatological diseases, we found out that there are not currently sufficient eligible studies confirming the role of JAK inhibitors in the treatment of chronic urticaria. There is therefore a need for more studies regarding the efficacy and safety of these medications in the treatment of refractory chronic urticaria.

Simple Summary: Our study aimed to stain a cellular pathway that is a potential target of drugs to treat allergies. In our study, we took skin samples from dogs allergic to dust, before and after exposure to dust mites, and stained those samples for this pathway. We found that this pathway was present in skin cells and that exposure to the dust mites changed how this pathway was expressed. These results confirm that this pathway plays a role in the course of allergic responses and that topical creams targeting this pathway can be promising to treat allergic skin disease. Janus kinase (JAK) pathways have emerged as targets of treatment, yet localization and expression of JAK1 and JAK3 in canine atopic skin have not been studied. This study aimed to compare the localization and expression of JAK1 and JAK3 in the skin of atopic dogs before and after allergen exposure. Skin biopsies taken from atopic beagles sensitized to house dust mites (HDM) before (D0) and after four weeks (D28) of allergen exposure were stained. Staining was subjectively scored by examiners unaware of the source of the slides. Image J was used for the semiquantitative assessment of staining intensity. JAK1 and JAK3 staining was epidermal and dermal. JAK1 staining was cytoplasmic, primarily found in basal keratinocytes and dermal cells, while JAK 3 was nuclear (all epidermal levels and on dermal inflammatory cells). Epidermal thickness was significantly higher on D28 than on D0 (p < 0.0001). For JAK1, epidermal staining divided by epithelial thickness was significantly lower on D28 (p = 0.0002) compared to D0. For JAK3 staining, intensity in the dermis was significantly higher on D28 (p = 0.0405) compared to D0. We conclude that decreased expression of JAK1 in the epidermis and increased expression of JAK3 in the dermis of atopic dogs occur after allergen exposure. [ABSTRACT FROM AUTHOR]

Crocin has been reported to have therapeutic effects on multiple cancers including colon cancer, but its specific mechanism is still ambiguous and needs to be further explored. Human colorectal adenocarcinoma cells (HCT-116) and human normal colonic epithelial cells (CCD841) were first treated with increasing concentrations of crocin. Subsequently, with 150 and 200 μM of crocin, the cell vitality was examined by cell counting kit 8. Cell apoptosis and proliferation were tested by TUNEL staining and colony formation assay, respectively. The expression of Ki-67 was assessed by immunofluorescence. Enzyme-linked immunosorbent assay was used to evaluate the level of inflammation- and oxidative-related factors. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were examined by flow cytometer. Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), and extracellular regulated protein kinases (ERK) in HCT-116 cells were tested by Western blot. Different concentrations of crocin barely affected the CCD841 cell vitality, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner. Moreover, the contents of inflammation- and oxidative-related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS and restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression in HCT-116 cells. Crocin induced apoptosis and restored mitochondrial function in HCT-116 cells via repressing the JAK pathway. If the threptic effect works in patients, it could herald a new, effective treatment for colon cancer, improving the patients’ prognosis and quality of life.

Janus kinase (JAK) pathways have emerged as targets of treatment, yet localization and expression of JAK1 and JAK3 in canine atopic skin have not been studied. This study aimed to compare the localization and expression of JAK1 and JAK3 in the skin of atopic dogs before and after allergen exposure. Skin biopsies taken from atopic beagles sensitized to house dust mites (HDM) before (D0) and after four weeks (D28) of allergen exposure were stained. Staining was subjectively scored by examiners unaware of the source of the slides. Image J was used for the semiquantitative assessment of staining intensity. JAK1 and JAK3 staining was epidermal and dermal. JAK1 staining was cytoplasmic, primarily found in basal keratinocytes and dermal cells, while JAK 3 was nuclear (all epidermal levels and on dermal inflammatory cells). Epidermal thickness was significantly higher on D28 than on D0 (p < 0.0001). For JAK1, epidermal staining divided by epithelial thickness was significantly lower on D28 (p = 0.0002) compared to D0. For JAK3 staining, intensity in the dermis was significantly higher on D28 (p = 0.0405) compared to D0. We conclude that decreased expression of JAK1 in the epidermis and increased expression of JAK3 in the dermis of atopic dogs occur after allergen exposure.

Purpose: The Coronavirus disease 2019 (COVID-19) pandemic is one of the most devastating global problems. Regarding the lack of disease-specific treatments, repurposing drug therapy is currently considered a promising therapeutic approach in pandemic situations. Recently, the combination therapy of Janus kinase (JAK) inhibitor baricitinib has been authorized for emergency COVID-19 hospitalized patients; however, this strategy's safety, drug-drug interactions, and cellular signaling pathways remain a tremendous challenge. Methods: In this study, we aimed to provide a deep insight into the baricitinib combination therapies in severe COVID-19 patients through reviewing the published literature on PubMed, Scopus, and Google scholar databases. We also focused on cellular and subcellular pathways related to the synergistic effects of baricitinib plus antiviral agents, virus entry, and cytokine storm (CS) induction. The safety and effectiveness of this strategy have also been discussed in moderate to severe forms of COVID-19 infection. Results: The severity of COVID-19 is commonly associated with a dysregulated immune response and excessive release of pro-inflammatory agents, resulting in CS. It has been shown that baricitinib combined with antiviral agents could modulate the inflammatory response and provide a series of positive therapeutic outcomes in hospitalized adults and pediatric patients (age ≥ two years old). Conclusion: Baricitinib plus the standard of care treatment might be a potential strategy in hospitalized patients with severe COVID-19. [ABSTRACT FROM AUTHOR]

• Therapeutic activation of the JAK proteins can regulate cytokine-driven inflammation. • Janus kinase inhibitors are a new class of small molecules drugs. • Janus kinase inhibitors are emerging as a new therapeutic approach to manage rheumatoid arthritis. • Current available treatments for rheumatoid arthritis such as DMARDs have lost their primary reaction. Rheumatoid arthritis is a world leading cause of musculoskeletal disease. With the introduction of biological agents as treatment alternatives the clinical possibilities have grown exponentially. Currently most common Disease-modifying anti-rheumatic drugs (DMARDs) treatment option involves intravenous or subcutaneous injection, and some patients struggle to respond to DMARDs or lose their primary reaction. An oral drug formulation with lowered costs of manufacturing and flexibility for healthcare workers to preferably perform treatment will result in decreased healthcare expenditures and increased medication compliance. The JAK-STAT inhibitors, a new class of small molecules drugs, fulfills these criteria and has recently shown efficacy in rheumatoid arthritis. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical trials. Convincing clinical results suggest that therapeutic inhibition of the JAK proteins can effectively modulate a complex cytokine-driven inflammation. [ABSTRACT FROM AUTHOR]