Staphylococcal trafficking and infection-from 'nose to gut' and back

Staphylococcus aureus is an opportunistic human pathogen, which is a leading cause of infections worldwide. The challenge in treating S. aureus infection is linked to the development of multidrug-resistant strains and the mechanisms employed by this pathogen to evade the human immune defenses. In addition, S. aureus can hide asymptomatically in particular ‘protective’ niches of the human body for prolonged periods of time. In the present review, we highlight recently gained insights in the role of the human gut as an endogenous S. aureus reservoir next to the nasopharynx and oral cavity. In addition, we address the contribution of these ecological niches to staphylococcal transmission, including the roles of particular triggers as modulators of the bacterial dissemination. In this context, we present recent advances concerning the interactions between S. aureus and immune cells to understand their possible roles as vehicles of dissemination from the gut to other body sites. Lastly, we discuss the factors that contribute to the switch from colonization to infection. Altogether, we conclude that an important key to uncovering the pathogenesis of S. aureus infection lies hidden in the endogenous staphylococcal reservoirs, the trafficking of this bacterium through the human body and the subsequent immune responses

What makes (hydroxy)chloroquine ineffective against COVID-19:Insights from cell biology

Since chloroquine (CQ) and hydroxychloroquine (HCQ) can inhibit the invasion and proliferation of SARS-CoV-2 in cultured cells, the repurposing of these antimalarial drugs was considered a promising strategy for treatment and prevention of COVID-19. However, despite promising preliminary findings, many clinical trials showed neither significant therapeutic nor prophylactic benefits of CQ and HCQ against COVID-19. Here, we aim to answer the question of why these drugs are not effective against the disease by examining the cellular working mechanisms of CQ and HCQ in prevention of SARS-CoV-2 infections

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially

Cytokine producing B-cells and their capability to polarize macrophages in giant cell arteritis

OBJECTIVE: The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines.METHODS: The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro.RESULTS: The presence of IL-6, GM-CSF, TNFα, IFNγ, LTβ and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1β, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells.CONCLUSION: B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.</p

Controlled homeodynamic concept using a conformable calculus in artificial biological systems

Homeodynamic system (HS) in the biological studies (from the Greek homoios (similar) and Dynamis (energy)) designates the accommodating instruments of stabilizing and repairing of the fundamental reliability and functional efficiency of living schemes. In this effort, we employ the concept of conformable calculus (CC) to generalize the homeodynamic system. The generalization requires a controller in the system to preserve the variables robustly regulated, oscillated, and synchronized variables at a certain set point. Here, we show how the selectivity of the CC makes differences in the behavior of an oscillation and the other properties of HS

Dynamical system of the growth of COVID-19 with controller

Recently, various studied were presented to describe the population dynamic of covid-19. In this effort, we aim to introduce a different vitalization of the growth by using a controller term. Our method is based on the concept of conformable calculus, which involves this term. We investigate a system of coupled differential equations, which contains the dynamics of the diffusion among infected and asymptomatic characters. Strong control is considered due to the social separation. The result is consequently associated with a macroscopic law for the population. This dynamic system is useful to recognize the behavior of the growth rate of the infection and to confirm if its control is correctly functioning. A unique solution is studied under self-mapping properties. The periodicity of the solution is examined by using integral control and the optimal control is discussed in the sequel.</p

Dynamical system of the growth of COVID-19 with controller

Recently, various studied were presented to describe the population dynamic of covid-19. In this effort, we aim to introduce a different vitalization of the growth by using a controller term. Our method is based on the concept of conformable calculus, which involves this term. We investigate a system of coupled differential equations, which contains the dynamics of the diffusion among infected and asymptomatic characters. Strong control is considered due to the social separation. The result is consequently associated with a macroscopic law for the population. This dynamic system is useful to recognize the behavior of the growth rate of the infection and to confirm if its control is correctly functioning. A unique solution is studied under self-mapping properties. The periodicity of the solution is examined by using integral control and the optimal control is discussed in the sequel

Solvability and stability of a fractional dynamical system of the growth of COVID-19 with approximate solution by fractional Chebyshev polynomials

Lately, many studies were offered to introduce the population dynamics of COVID-19. In this investigation, we extend different physical conditions of the growth by employing fractional calculus. We study a system of coupled differential equations, which describes the dynamics of the infection spreading between infected and asymptomatic styles. The healthy population properties are measured due to the social meeting. The result is associated with a macroscopic law for the population. This dynamic system is appropriate to describe the performance of growth rate of the infection and to verify if its control is appropriately employed. A unique solution, under self-mapping possessions, is investigated. Approximate solutions are presented by utilizing fractional integral of Chebyshev polynomials. Our methodology is based on the Atangana–Baleanu calculus, which provides various activity results in the simulation. We tested the suggested system by using live data. We found positive action in the graphs