ABSTRACT
The outbreak of COVID-19 has prompted a substantial shrinkage in various businesses worldwide, the perishable food sector being one of the worst hits. Henceforth, this manuscript intends to analyse the impact of COVID-19 on perishable food supply chains (PFSCs) of developed and developing countries. For this, the study presents the analysis in two steps. In the first step, the study illuminates the particular factors that frame unique sorts of supply chain (SC) disturbances in PFSC. Secondly, the study proposes a unique interval-valued intuitionistic fuzzy set (IVIFS)-based graph theory and matrix approach (GTMA) to analyse the COVID-19 impact index value. In addition to this, the PERMAN algorithm is used to calculate the permanent function. The study has revealed that developing nations should focus more on their technological and infrastructural factors to improve the condition of PFSC during the pandemic. This study's results can be deployed by decision-makers to forestall the operative and long-haul consequences of COVID-19, or any other disruptions to the PFSC, and make plans to overcome the impact. The significance of this manuscript is that the prominent factors degrading the performance of PFSC amidst the pandemic have been highlighted, with their respective impact on developed and developing nations compared. Moreover, a neoteric comprehensive integration of IVIFS-GTMA technique along with the PERMAN algorithm has been utilised in this manuscript. This particular study is inimitable as it supplements existing literature by providing analytical support to the relationship among various factors impacting the PFSC amidst the pandemic.
ABSTRACT
Haemoglobin (Hb) has well-documented inflammatory effects and is normally efficiently scavenged; clearance mechanisms can be overwhelmed during erythrocyte lysis. Whether Hb is preferentially inflammatory in lupus and triggers broad anti-self responses was assessed. Peripheral blood mononuclear cells (PBMCs) derived from SLE patients secreted higher levels of lupus-associated inflammatory cytokines when incubated with human Hb than did PBMCs derived from healthy donors, an effect negated by haptoglobin. Ferric murine Hb triggered the preferential release of lupus-associated cytokines from splenocytes, B cells, CD4 T cells, CD8 T cells and plasmacytoid dendritic cells isolated from ageing, lupus-prone NZM2410 mice, and also had mitogenic effects on B cells. Pull-downs, followed by mass spectrometry, revealed interactions of Hb with several lupus-associated autoantigens; co-incubation of ferric Hb with apoptotic blebs (structures that contain packaged autoantigens) revealed synergies-in terms of cytokine release and autoantibody production in vitro-that were also restricted to the lupus genotype. Murine ferric Hb activated multiple signalling pathways and, in combination with apoptotic blebs, preferentially triggered MAP kinase signalling specifically in splenocytes isolated from lupus-prone mice. Infusion of murine ferric Hb into lupus-prone mice led to enhanced release of lupus-associated cytokines, the generation of a spectrum of autoantibodies and enhanced-onset glomerulosclerosis. Given that the biased recognition of ferric Hb in a lupus milieu, possibly in concert with lupus-associated autoantigens, triggers inflammatory responses and the generation of lupus-associated cytokines, and also stimulates the generation of potentially pathogenic lupus-associated autoantibodies, neutralization of Hb could have beneficial effects.
Subject(s)
Autoantigens/immunology , Hemoglobins/metabolism , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/etiology , Lupus Nephritis/metabolism , Animals , Apoptosis/genetics , Apoptosis/immunology , Autoantibodies/immunology , Biomarkers , Cytokines/metabolism , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Disease Susceptibility , Humans , Imidazoles/pharmacology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/immunology , Lupus Nephritis/pathology , Lymphocyte Activation/immunology , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Mice , Protein Binding , Signal Transduction , Spleen/immunology , Spleen/metabolismABSTRACT
Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunological consequences, particularly in the context of pre-existing lupus. IgG anti-Hb responses were detected in the sera of lupus patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric (Fe3+) Hb triggered preferential release of lupus-associated cytokines from splenocytes derived from aging lupus-prone mice. Anti-Hb B cell precursor frequencies were heightened in such mice, which also expressed increased titers of anti-Hb antibodies in serum and in kidney eluates. Fe3+ Hb preferentially increased the functional maturation of bone marrow-derived dendritic cells (BMDCs) from lupus-prone mice, effects abrogated upon the inhibition of Stat3. Hb interacted with lupus-associated autoantigens extruded during apoptosis and coincubation of Hb and apoptotic blebs had additional maturation-inducing effects on lupus BMDCs. Immunization with Hb in lupus-prone mice induced antigen spreading to lupus-associated moieties; Hb-interacting autoantigens were preferentially targeted and increased complement deposition and glomerulosclerosis were observed. Hb therefore demonstrates both antigenicity and immunogenicity and triggers specific immuno-pathological effects in a lupus milieu.
