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Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. https://www.selleckchem.com/products/PD-173074.html Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as from COVID-19 patients, but classification was not successful in distinguishing those patients with early Lyme disease cases that would advance to develop post-treatment persistent symptoms.Interleukin-2 (IL-2) expands the depleted T regulatory (Treg) cell population, and it has emerged as a potential therapy in systemic lupus erythematosus (SLE). However, IL-2 administration may involve the risk of expanding unwanted pro-inflammatory cells. We herein studied the effects of IL-2 on pro-inflammatory cytokine production by CD4+ and CD8+ T cells in parallel with Treg development following CD3/CD28 co-stimulation. While Treg cells are depleted in SLE patients, their CD4+ T cells were poised to receive and activate IL-2 signaling as evidenced by upregulation of CD25 and enhanced IL-2-incued STAT5 phosphorylation during Treg differentiation. In patients with SLE, however, IL-2 also expanded CD8+ T cells capable of producing interleukin-5, interkeukin-13 (IL-13), and interferon-γ (IFN-γ) that occurred with enhanced expression of GATA-3 and phosphorylation of STAT6 but not STAT5. Our data pinpoint a safety signal for systemic administration of IL-2 and challenges a long-held conceptual platform of type 1 and 2 cytokine antagonism by newly documenting the IL-2-dependent development of IL-13 and IFN-γ double-positive (IL-13+IFNγ+) CD8+ T cells in SLE.Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.Despite of the rapid development of the vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it will take several months to have enough doses and the proper infrastructure to vaccinate a good proportion of the world population. In this interim, the accessibility to the Bacille Calmette-Guerin (BCG) may mitigate the pandemic impact in some countries and the BCG vaccine offers significant advantages and flexibility in the way clinical vaccines are administered. BCG vaccination is a highly cost-effective intervention against tuberculosis (TB) and many low-and lower-middle-income countries would likely have the infrastructure, and health care personnel sufficiently familiar with the conventional TB vaccine to mount full-scale efforts to administer novel BCG-based vaccine for COVID-19. This suggests the potential for BCG to overcome future barriers to vaccine roll-out in the countries where health systems are fragile and where the effects of this new coronavirus could be catastrophic. Many studies have reported cross-protective effects of the BCG vaccine toward non-tuberculosis related diseases. Mechanistically, this cross-protective effect of the BCG vaccine can be explained, in part, by trained immunity, a recently discovered program of innate immune memory, which is characterized by non-permanent epigenetic reprogramming of macrophages that leads to increased inflammatory cytokine production and consequently potent immune responses. In this review, we summarize recent work highlighting the potential use of BCG for the treatment respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials. In situations where no other specific prophylactic tools are available, the BCG vaccine could be used as a potential adjuvant, to decrease sickness of SARS-CoV-2 infection and/or to mitigate the effects of concurrent respiratory infections.Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.
Read More: https://www.selleckchem.com/products/PD-173074.html
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