Kimia Alizadeh

Bio: Kimia Alizadeh is an academic researcher from Kansas State University. The author has contributed to research in topics: Inflammation & Cytokine storm. The author has an hindex of 1, co-authored 5 publications receiving 1 citations.

Cytokine Storm Syndrome in SARS-CoV-2 Infections: A Functional Role of Mast Cells.

Abstract: Cytokine storm syndrome is a cascade of escalated immune responses disposing the immune system to exhaustion, which might ultimately result in organ failure and fatal respiratory distress. Infection with severe acute respiratory syndrome-coronavirus-2 can result in uncontrolled production of cytokines and eventually the development of cytokine storm syndrome. Mast cells may react to viruses in collaboration with other cells and lung autopsy findings from patients that died from the coronavirus disease that emerged in 2019 (COVID-19) showed accumulation of mast cells in the lungs that was thought to be the cause of pulmonary edema, inflammation, and thrombosis. In this review, we present evidence that a cytokine response by mast cells may initiate inappropriate antiviral immune responses and cause the development of cytokine storm syndrome. We also explore the potential of mast cell activators as adjuvants for COVID-19 vaccines and discuss the medications that target the functions of mast cells and could be of value in the treatment of COVID-19. Recognition of the cytokine storm is crucial for proper treatment of patients and preventing the release of mast cell mediators, as impeding the impacts imposed by these mediators could reduce the severity of COVID-19.

The Roles of Neutrophils in Cytokine Storms

Abstract: A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.

Functional Characterization of Multiple Ehrlichia chaffeensis Sodium (Cation)/Proton Antiporter Genes Involved in the Bacterial pH Homeostasis.

Abstract: Ehrlichia chaffeensis causes human monocytic ehrlichiosis. Little is known about how this and other related tick-borne rickettsia pathogens maintain pH homeostasis in acidified phagosomes and the extracellular milieu. The membrane-bound sodium (cation)/proton antiporters are found in a wide range of organisms aiding pH homeostasis. We recently reported a mutation in an antiporter gene of E. chaffeensis (ECH_0379) which causes bacterial in vivo attenuation. The E. chaffeensis genome contains 10 protein coding sequences encoding for predicted antiporters. We report here that nine of these genes are transcribed during the bacterial growth in macrophages and tick cells. All E. chaffeensis antiporter genes functionally complemented antiporter deficient Escherichia coli. Antiporter activity for all predicted E. chaffeensis genes was observed at pH 5.5, while gene products of ECH_0179 and ECH_0379 were also active at pH 8.0, and ECH_0179 protein was complemented at pH 7.0. The antiporter activity was independently verified for the ECH_0379 protein by proteoliposome diffusion analysis. This is the first description of antiporters in E. chaffeensis and demonstrates that the pathogen contains multiple antiporters with varying biological functions, which are likely important for the pH homeostasis of the pathogen’s replicating and infectious forms.

Dendritic Cells : Key to Cancer Immunotherapy

Abstract: www.thecancerpress.com Corresponding Author E-Mail: k.alizadeh95@gmail.com 6 References 1. Appay V, Douek DC, Price DA. CD8+ T cell efficacy in vaccination and disease. Nat Med. 2008;14(6):623-8. 2. Ariizumi K, Shen G-L, Shikano S, Xu S, Ritter R, Kumamoto T, et al. Identification of a Novel, Dendritic Cellassociated Molecule, Dectin-1, by Subtractive cDNA Cloning. Journal of Biological Chemistry. 2000;275 (26):20157-67. 3. Ashley DM, Faiola B, Nair S, Hale LP, Bigner DD, Gilboa E. Bone Marrow–generated Dendritic Cells Pulsed with Tumor Extracts or Tumor RNA Induce Antitumor Immunity against Central Nervous System Tumors. The Journal of Experimental Medicine. 1997;186(7):1177-82. Vol 3, No 1, March, 2017, P 6-12 DOI, 10.15562/tcp.37 Review Paper Vol. 3, No.1, March, 2017

COVID-19 Vaccination in Patients With Malignancy; A Systematic Review and Meta-Analysis of the Efficacy and Safety

Abstract: Background Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes. Methods A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies. Results A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively. Conclusion Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy.

The Utility of Laboratory Parameters for Cardiac Inflammation in Heart Failure Patients Hospitalized with SARS-CoV-2 Infection

Abstract: COVID-19 has been associated with cardiovascular consequences, including myocardial infarction, thromboembolic events, arrhythmia, and heart failure. Numerous overlapping mechanisms, such as the IL-6 dependent cytokine storm and unopposed angiotensin II stimulation, could be responsible for these consequences. Cardiac damage is hypothesized to be a consequence of the direct viral infection of cardiomyocytes, resulting in increased metabolic demand, immunological activation, and microvascular dysfunction. Patients with pre-existing chronic heart failure are therefore at increased risk of decompensation, further heart damage, and significant health deterioration. Based on the aforementioned assumptions, we developed a study aiming to provide a detailed description of changes in biological parameters and cardiac injury markers of patients with heart failure and SARS-CoV-2 infection by correlating them with the clinical presentation and COVID-19 vaccination status, to predict the probability of ICU admission based on their initial hospital presentation. A two-year retrospective study was performed on heart failure patients with a history of SARS-CoV-2 infection and detailed records of biological biomarkers; a total of 124 eligible patients with COVID-19 and 236 without COVID-19 were recruited. Patients with heart failure and SARS-CoV-2 infection had significantly elevated baseline biological parameters and cardiac markers compared to those without COVID-19. Several cardiac injury markers were identified as significant independent risk factors for ICU admission: CK-MB (HR = 4.1, CI [2.2–6.9]), myoglobin (HR = 5.0, CI [2.3–7.8]), troponin-I (HR = 7.1 [4.4–9.6]), troponin-T (HR = 4.9, CI [1.7–7.4]). The elevation of a basic panel of acute inflammation markers (CRP, IL-6, fibrinogen), D-dimers, and BNP was also a significant risk factor. The follow-up of survivors at four weeks after viral clearance determined a worsened clinical picture by NYHA classification, worsened cardiac ultrasound findings, and a mild improvement in cardiac and inflammatory markers. Increased levels of myocardial damage parameters in association with cardiac ultrasound findings and basic inflammatory markers may enable early risk assessment and triage in hospitalized heart failure patients infected with SARS-CoV-2.

Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection

Abstract: Post-COVID syndrome or long COVID is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection, the pathogen responsible for coronavirus disease. The content herein presented reviews the reported long-term consequences and aftereffects of COVID-19 infection and the potential strategies to adopt for their management. Recent studies have shown that severe forms of COVID-19 can progress into acute respiratory distress syndrome (ARDS), a predisposing factor of pulmonary fibrosis that can irreversibly compromise respiratory function. Considering that the most serious complications are observed in the airways, the inhalation delivery of drugs directly to the lungs should be preferred, since it allows to lower the dose and systemic side effects. Although further studies are needed to optimize these techniques, recent studies have also shown the importance of in vitro models to recreate the SARS-CoV-2 infection and study its sequelae. The information reported suggests the necessity to develop new inhalation therapies in order to improve the quality of life of patients who suffer from this condition.

Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy

Abstract: Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota–immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota–immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.