scholarly journals Coenzyme Q10 and Vitamin D Interventions Could Ameliorate COVID-19 Related Cellular Bioenergetic Dysfunction and Cytokine Storms

2021 ◽  
Vol 1 (6) ◽  
pp. 1-9
Author(s):  
Darshna Yagnik
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Coenzyme Q10 ◽  
Immune Cell ◽  
Chronically Ill ◽  
Abnormal Immune Response ◽  
Cell Immunity ◽  
Tract Infections ◽  
Spread Of Infection ◽  
Cell Phenotypes

The immune response to SARS-CoV-2 varies from asymptomatic or mild symptoms of high temperature, muscle aches and coughs lasting 7 to 14 days to lower respiratory tract infections leading to pneumonia and serious respiratory distress as well as long COVID-19. Complications occur due to an abnormal immune response which involves upregulation of multiple cytokines leading to sustained inflammation which results in the spread of infection to vital organs. The double vaccine roll out has been rapid however vaccine mediated antibodies are not 100% effective against future coronavirus variants which may become increasingly more resistant and easily transmissible to overcome host immunity. Invariably supportive therapies will be needed. Research has shown that coenzyme Q10 and vitamin D deficiencies can have detrimental effects on immune cell defence, function and cytokine secretion promoting inflammation and sepsis especially against microbes. Early interventions including supplementation of these factors could mitigate cellular dysfunction especially in relation to mitochondria bioenergetics and help maintain cell immunity. This is particularly important as chronically ill COVID-19 patients seem to display abnormal immune cell phenotypes in infected organs indicating this could contribute to disease progression. The immune response and proposed roles of Vitamin D and Coenzyme Q10 in COVID-19 are discussed.

scholarly journals B Cells in Patients With Melanoma: Implications for Treatment With Checkpoint Inhibitor Antibodies

2021 ◽  
Vol 11 ◽  
Author(s):  
Zena N. Willsmore ◽  
Robert J. Harris ◽  
Silvia Crescioli ◽  
Khuluud Hussein ◽  
Helen Kakkassery ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Response To Treatment ◽  
Cell Immunity ◽  
Cell Phenotypes

The contributions of the humoral immune response to melanoma are now widely recognized, with reports of positive prognostic value ascribed to tumor-infiltrating B cells (TIL-B) and increasing evidence of B cells as key predictors of patient response to treatment. There are disparate views as to the pro- and anti-tumor roles of B cells. B cells appear to play an integral role in forming tumor-associated tertiary lymphoid structures (TLSs) which can further modulate T cell activation. Expressed antibodies may distinctly influence tumor regulation in the tumor microenvironment, with some isotypes associated with strong anti-tumor immune response and others with progressive disease. Recently, B cells have been evaluated in the context of cancer immunotherapy. Checkpoint inhibitors (CPIs), targeting T cell effector functions, have revolutionized the management of melanoma for many patients; however, there remains a need to accurately predict treatment responders. Increasing evidence suggests that B cells may not be simple bystanders to CPI immunotherapy. Mature and differentiated B cell phenotypes are key positive correlates of CPI response. Recent evidence also points to an enrichment in activatory B cell phenotypes, and the contribution of B cells to TLS formation may facilitate induction of T cell phenotypes required for response to CPI. Contrastingly, specific B cell subsets often correlate with immune-related adverse events (irAEs) in CPI. With increased appreciation of the multifaceted role of B cell immunity, novel therapeutic strategies and biomarkers can be explored and translated into the clinic to optimize CPI immunotherapy in melanoma.

scholarly journals Dietary L-Tryptophan Regulates Colonic Serotonin Homeostasis in Mice with Dextran Sodium Sulfate-Induced Colitis

2020 ◽  
Vol 150 (7) ◽  
pp. 1966-1976 ◽  
Author(s):  
Bin Wang ◽  
Shiqiang Sun ◽  
Moyan Liu ◽  
Hui Chen ◽  
Ning Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drinking Water ◽  
Immune Responses ◽  
Sodium Sulfate ◽  
Serotonin Receptor ◽  
Immune Cell ◽  
Dextran Sodium Sulfate ◽  
Stat3 Signaling ◽  
Underlying Mechanisms ◽  
Cell Phenotypes

ABSTRACT Background L-tryptophan (Trp) has been reported to regulate gut immune responses during inflammation. However, the underlying mechanisms are largely unknown. Objective We investigated the role of Trp supplementation on the serotonin receptor (HTR)-mediated immune response in the colon of mice with dextran sodium sulfate (DSS)-induced colitis. Methods In Experiment 1, male C57BL/6 mice were randomly assigned to 1 of 4 groups: Control (Con) or L-Trp supplementation [0.1 mg/(g body weight·d) in drinking water] (Trp) with (+DSS) or without 2% DSS in drinking water from days 8 to 14 of the 17-d study. In Experiments 2 and 3, Trp + DSS (Expt. 2) or DSS (Expt. 3) mice were treated as described above and subcutaneously administered with HTR1A or HTR4 antagonists (or their combination) or an HTR2 agonist from days 8 to 14 of the 15-d study. Changes in immune cell phenotypes, inflammatory mediators, and related cell signaling molecules were assessed by flow cytometry, real-time PCR, or Western blot. The mRNA abundances of Trp hydroxylase (Tph1), serotonin reuptake transporter (Slc6a4), and Htr in the colon were also assessed. Results Trp supplementation before DSS treatment upregulated the expression of colonic Slc6a4 (0.49 compared with 0.30), Htr1a (1.14 compared with 0.65), and Htr4 (1.08 compared with 0.70), downregulated the expression of Htr2a (1.54 compared with 1.89), and decreased the colonic serotonin concentration (11.5 compared with 14.8 nmol/g tissue) (P < 0.01). Trp regulated the DSS-induced immune response partly through attenuating the activation of toll-like receptor 4 (TLR4)-STAT3 signaling and nucleus p-65. Either an HTR2 agonist or HTR1A and HTR4 antagonists reversed the effects of Trp. Conclusions In mice treated with DSS, Trp supplementation before DSS administration improved colonic immune responses partly by reducing colonic serotonin and subsequent interactions with HTR1A and HTR4, which are known to be present on neutrophils and macrophages.

scholarly journals Skin Manifestations In Children With COVID-19: A Literature Review

2020 ◽  
Vol 10 (3) ◽  
Author(s):  
Poliana Poyanco
Keyword(s):  
Immune Response ◽  
Literature Review ◽  
New England ◽  
Pediatric Patients ◽  
Skin Involvement ◽  
Cutaneous Manifestations ◽  
Abnormal Immune Response ◽  
Spread Of Infection ◽  
Inflammatory Syndrome ◽  
Correlate Data

OBJECTIVES: Perform a literature review to correlate data on dermatological manifestations in pediatric patients with coronavirus disease 2019 (COVID-19). METHODS: A systematic literature review was performed, selecting articles involving COVID-19 and dermatological manifestations in pediatric patients, in databases such as PubMed, The New England Journal of Medicine, The British Medical Journal and The Lancet. RESULTS: Studies indicate that the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) can cause dermatological manifestations, like macules, papules, rash, hives, erythema and oral mucositis. Skin involvement by COVID-19 in children may be associated with multisystemic inflammatory syndrome, in which there is an abnormal immune response associated of cytokines and activation of macrophages, which can justify the changes in the skin. CONCLUSION: Cutaneous manifestations, although unspecific, are important for the identification of the disease in pediatric patients and better control of the spread of infection to the population.

scholarly journals Prophylactic and Therapeutic Role of Vitamin D Supplementation in COVID-19: A Review

2021 ◽  
Vol 3 (4) ◽  
pp. 18-26
Author(s):  
Mehrie Harshad Patel ◽  
Sakshi Mishra ◽  
Ketul S. Barot ◽  
Saloni H. Naik ◽  
Angelina Browne ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Respiratory Tract ◽  
Vitamin D Deficiency ◽  
Inflammatory Cytokines ◽  
Adaptive Immune Response ◽  
Vitamin D Supplementation ◽  
Therapeutic Role ◽  
Vitamin D Levels ◽  
Tract Infections

Looking at the current scenario of the global pandemic with Coronavirus Disease 2019 (COVID-19) and the dramatic rise of variant COVID-19 cases it is reasonable to reason that one’s immunity (innate, adaptive, or passive) plays a vital role in an individual’s susceptibility as well as the severity. While the population is getting passively immunized with vaccination, the innate and adaptive immune response should also be emphasized. Vitamins and minerals play an important role in developing and modulating the immune response in the human body. Of which, one is, Vitamin D. Besides playing a major role in Calcium metabolism, Vitamin D is involved in modulating various immune system pathways to contain the virus, which includes dampening Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry and replication, reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines, increasing the synthesis of a natural antimicrobial peptide, and activating protective cells such as macrophages that can kill SARS-CoV-2. Vitamin D also possesses a neuroprotective property that is linked to the modulation of neurotrophins. In the current situation of the pandemic, an important connection between Vitamin D deficiency and poor health outcomes in COVID-19 patients have been reported. Furthermore, adequate Vitamin D levels were linked to a lower risk of unconsciousness and hypoxia. Vitamin D deficiency affects over half of the world's population. A low serum concentration of Vitamin D is a risk factor for acute respiratory tract infection. Vitamin D supplementation, on the other hand, is linked to a reduced risk of acute respiratory tract infections. Here, we conducted a literature review of publicly available information to summarize the link between Vitamin D levels and the severity of COVID-19 infection. The main objective of this manuscript is to review and provide information reported by published literature from publically available papers on online databases regarding the significance of Vitamin D in immune response and its prophylactic and therapeutic role in the management of COVID-19.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Injury-Induced Innate Immune Response During Segment Regeneration of the Earthworm, Eisenia andrei

2021 ◽  
Vol 22 (5) ◽  
pp. 2363
Author(s):  
Kornélia Bodó ◽  
Zoltán Kellermayer ◽  
Zoltán László ◽  
Ákos Boros ◽  
Bohdana Kokhanyuk ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune Cell ◽  
Scavenger Receptor ◽  
Cell Renewal ◽  
Body Parts ◽  
Eisenia Andrei ◽  
Blastema Formation ◽  
Close Proximity ◽  
Renewal Period

Regeneration of body parts and their interaction with the immune response is a poorly understood aspect of earthworm biology. Consequently, we aimed to study the mechanisms of innate immunity during regeneration in Eisenia andrei earthworms. In the course of anterior and posterior regeneration, we documented the kinetical aspects of segment restoration by histochemistry. Cell proliferation peaked at two weeks and remitted by four weeks in regenerating earthworms. Apoptotic cells were present throughout the cell renewal period. Distinct immune cell (e.g., coelomocyte) subsets were accumulated in the newly-formed blastema in the close proximity of the apoptotic area. Regenerating earthworms have decreased pattern recognition receptors (PRRs) (e.g., TLR, except for scavenger receptor) and antimicrobial peptides (AMPs) (e.g., lysenin) mRNA patterns compared to intact earthworms. In contrast, at the protein level, mirroring regulation of lysenins became evident. Experimental coelomocyte depletion caused significantly impaired cell divisions and blastema formation during anterior and posterior regeneration. These obtained novel data allow us to gain insight into the intricate interactions of regeneration and invertebrate innate immunity.

scholarly journals Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyösti Tahkola ◽  
Maarit Ahtiainen ◽  
Jukka-Pekka Mecklin ◽  
Ilmo Kellokumpu ◽  
Johanna Laukkarinen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Geographical Area ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Negative Prognostic Factor ◽  
High Level ◽  
Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

scholarly journals AB0128 CXCL5 DAMPENS INFLAMMATION IN THE PRE-CLINICAL MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS VIA THE ORCHESTRAL EFFECT OF REGULATING NEUTROPHIL TRAFFICKING AND SUPPRESSING HELPER T CELL-MEDIATED IMMUNE RESPONSE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1365.2-1365
Author(s):  
X. Fan ◽  
D. Guo ◽  
C. T. Ng ◽  
A. Law ◽  
Z. Y. Poon ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Systemic Lupus ◽  
Helper T Cell ◽  
Clinical Model ◽  
Cell Mediated Immune Response

Background:Patients with systemic lupus erythematosus (SLE) suffer from severe morbidity and mortality1-4, either from the disease itself or from side effects of immunosuppression5. Discovery of novel effective therapies with less toxicity is an urgent need.Objectives:The aim of this study is to elucidate the therapeutic potential and working mechanism of cytokine CXCL5 in lupus mice.Methods:Treatment with CXCL5, bone marrow (BM)-MSCs, standard of care (SOC) with combination of methylprednisolone and cyclophosphamide was given to 16-week-old Faslprmice. Mice were monitored for 10 weeks. Splenic immune cell subsets were measured by flow cytometry. Circulating cytokine and immunoglobulin were detected by Luminex technology. Renal function was evaluated by urinary spot albumin creatinine ratio. In situ renal immune cell infiltration and complement 3 deposition were detected by Haematoxylin and Eosin (H&E) staining and immunohistochemistry.Results:CXCL5 demonstrated consistent and potent immunosuppressive capacity in suppressing SLE with reduced autoantibody secretion, lymphoproliferation and preserved kidney function. With further exploration, we proved that CXCL5 reduced the proliferation of helper T cells (TH1 and TH2) in thein vitrofunctional assay. When we administrated CXCL5 to lupus mice, it promoted the proliferation of regulatory T cells and reduced the proliferation of TH17 cells, macrophages and neutrophils. Multiple proinflammatory cytokines including IL-2, IL-6, IL-12, IL-17A, KC/CXCL1, MIP-1β/CCL4 and TNF-α were also reduced. When combined with SOC, CXCL5 boosted its therapeutic effect and reduced the relevant indices of disease activity. When we correlated the effect of four different treatment groups (CXCL5, BM-MSCs, SOC, and CXCL5 plus SOC) on mice survival and target cell changes, we found that TH17 cells were the key effector cells involved in the pathogenesis of SLE.Conclusion:These findings demonstrated that CXCL5 dampens inflammation in the pre-clinical model of systemic lupus erythematosus via the orchestral effect of regulating neutrophil trafficking and suppressing helper T cell-mediated immune response. Administrating exogenous CXCL5 might be an attractive option to treat patients with lupus.References:[1]Ji S, Guo Q, Han Y, Tan G, Luo Y, Zeng F. Mesenchymal stem cell transplantation inhibits abnormal activation of Akt/GSK3beta signaling pathway in T cells from systemic lupus erythematosus mice.Cell Physiol Biochem.2012;29(5-6):705-712.[2]Peng SL. Altered T and B lymphocyte signaling pathways in lupus.Autoimmun Rev.2009;8(3):179-183.[3]Ferucci ED, Johnston JM, Gaddy JR, et al. Prevalence and incidence of systemic lupus erythematosus in a population-based registry of American Indian and Alaska Native people, 2007-2009.Arthritis Rheumatol.2014;66(9):2494-2502.[4]Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality.Arthritis Care Res (Hoboken).2012;64(2):159-168.[5]Sattwika PD, Mustafa R, Paramaiswari A, Herningtyas EH. Stem cells for lupus nephritis: a concise review of current knowledge.Lupus.2018;27(12):1881-1897.Acknowledgments:The work was supported by SMART II Centre Grant (NMRC/CG/M011/2017_SGH) and SingHealth Foundation (SHF/FG638P/2016).Disclosure of Interests:None declared

scholarly journals Vitamin D Status and Its Role in First-Time and Recurrent Urinary Tract Infections in Children: A Case-Control Study

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 419
Author(s):  
Carmen Muntean ◽  
Maria Săsăran
Keyword(s):  
Vitamin D ◽  
Urinary Tract ◽  
Case Control Study ◽  
Case Control ◽  
Study Group ◽  
Recurrent Utis ◽  
Vitamin D Levels ◽  
Tract Infections ◽  
First Time ◽  
Control Study

Vitamin D has emerged as a key factor in innate immunity. Its involvement in the pathogenesis of urinary tract infections (UTIs) has gained a lot of attention recently. The objective of this study is to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and first-time or recurrent UTIs in children. A prospective, case-control study was conducted on 101 pediatric patients, who were divided into two groups: 59 patients with UTIs and 42 age-matched healthy controls. Serum 25(OH)D was determined in each child and expressed in ng/mL. Vitamin D presented significantly lower values in study group subjects than in healthy controls (p < 0.01). Moreover, a significantly higher prevalence of vitamin D insufficiency and deficiency was found in children with UTIs (p < 0.01). Patients with recurrent UTIs presented significantly lower levels of vitamin D than those with first-time UTIs (p = 0.04). Urinary tract abnormalities did not seem to exercise an additional effect upon vitamin D levels within the study group. In conclusion, first-time and recurrent UTIs are associated with lower vitamin D levels. Further studies are necessary to validate our findings, as well as future longitudinal research regarding efficacy of vitamin D supplementation in children with UTIs.

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