Basic – ASSET

Role of scavenger receptor CD36 in microparticle-mediated in Decompression Sickness neuropathology

admin — Fri, 26 Dec 2025 09:18:26 +0000

Blood-borne microparticles (MPs) play a role in several forms of brain injury, but how they interact with the vasculature and con-tribute to neuroinﬂammation is unknown. The scavenger receptor CD36 is expressed across various cell types and regulates inﬂammation, vascular function, and innate immunity. We hypothesized that CD36 mediates MPs-induced neuroinﬂammatory responses in a murine model of decompression sickness (DCS). Wild-type mice subjected to decompression and naïve mice injected with MPs from decompressed mice exhibited a 2.2 ± 0.5-fold elevation in perivascular MPs deposition, 2.8 ± 0.6-fold elevation of inﬂammatory MPs in blood and 2.4 ± 0.4-fold in cervical lymph nodes, 2.7 ± 0.6-fold increase in neutrophil activation,2.0 ± 0.3-fold increased glymphatic ﬂow, 3.1 ± 0.4-fold increased leakage of six megadalton dextran at the blood-brain barrier, and a doubling of inﬂammatory proteins in brain. These events failed to occur in CD36 knockout mice and those conditionally deﬁcient in endothelial CD36 (FLOX). We conclude that inﬂammatory MPs interact with endothelial CD36 to mediate neuroinﬂammatory responses and vascular injury in DCS

Authors List :

Abid Bhat1, Stephen Thom1

Presenting Author :

Abid Bhat

Affiliations :

Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States

Email :

abidpharma8088@gmail.com

Key Words (5 Words Maximum) :

decompression; microglia; microparticles; neutrophil activation; scavenger receptor CD36

Ginger Extract Modulates Interferon -1 Signaling Pathway in Hepatocellular Carcinoma Cells-Derived from Caucasian, Asian, and African American Patients.

admin — Mon, 11 Dec 2023 16:53:11 +0000

Introduction: Hepatocellular Carcinoma (HCC) is a highly fatal disease in which race/ethnicity plays a vital role in determining incidence, mortality, and survival rates. The incidence of HCC is highest in Asia and Africa. Furthermore, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic white patients. To understand the underlying cause, we performed bioinformatics on existing gene expression data. We found that type I Interferon (IFN-I)-inflammatory signaling pathway showed statistically significant activation in AA/Black patients compared to white patients. Due to the severe toxicity of the currently available cancer treatments, there is also a demand for the development of alternative therapies with high efficacy and low side effects to treat liver cancer.
Hypothesis: We hypothesized that dietary compounds, because of their anti-inflammatory property, might modulate the IFN-I signaling pathway in HCC.
Objectives: To determine (a) effects of anti-inflammatory ginger extract on proliferation of HepG2 (white patient), Hep3B and O/20 (Black patients) and HuH-7 (Asian Patient) cell lines and investigate ginger effects on the INF-1 mediated signaling pathway.
Methods:  A dose-response of these extracts was used to determine IC50s on these cell lines using an MTT cell proliferation assay. Activation of INF-1-mediated downstream signaling proteins, including JAK1, TYK2, STAT1, and STAT2 phosphorylation status, was determined on a Western blot analysis. The expression of Interferon Signaling Genes (ISGs), including Myxovirus resistance gene 1 (MX1), 2′,5′-oligoadenylate synthetase (OAS1), Interferon-alpha inducible protein 6 (IFI6), and Interferon stimulated gene 15 (ISG15) was assayed using a quantitative Real-Time Polymerase Chain Reaction (RT-PCR).
Results: Ginger has a significantly (P<0.05) lower IC50s (g/ml) on cell lines from Black patients (Hep3B=160 ± 3, and O/20=162 ± 3) than cell lines from white (HepG2=176±5) or Asian (Hu7=174 ± 5) patients. Ginger treatment reduced the phosphorylation of IFN downstream mediators in all HCC cell lines. Furthermore, expression of MX1, ISG15, IF16, and OAS1 was also reduced in all HCC cells lines in a dose-dependent manner; however, the effects on gene expression were more sensitive to a lower concentration of ginger extract in Black patients derived HCC cell lines than other HCC cell lines.
Conclusions: Considering the role of pro-inflammatory and immunosuppressive functions of IFN-I, AA/Black HCC patients might benefit from combination of dietary anti-inflammatory agents and chemo/immunotherapy.
Future Directions: Currently, research is underway to identify the active chemical agent in ginger and test it on other patient-derived HCC lines and in an in vivo model.

Authors List :

Rafat Siddiqui, Sadia Kanwal, Eva Davis, Haiwen Li, Sueng Lee, Milton Faison, Devanand Sarkar

Presenting Author :

Rafat Siddiqui

Affiliations :

Food and Nutrition Science, Agricultural Research Station, and Department of Biology Virginia State University, Petersburg, VA 23806; and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298

Email :

rsiddiqui@vsu.edu

Key Words (5 Words Maximum) :

Liver cancer, Signal transduction, Interferon, Kinase

Prevalence of Medical Conditions Associated with COVID-19 Mortality in United States during 2020-2021

admin — Sun, 15 Aug 2021 20:35:49 +0000

Identifying the pre-existing comorbidities on coronavirus disease 2019 (COVID-19) mortality will help in developing the required treatment and promote the survival rate by COVID-19 population. This study focused on comprehensive meta-analysis of COVID-19 mortality in United States during 2020-2021 with 15 pre-existing comorbidities. We collected the data from World Health Organization Coronavirus (COVID-19) Dashboard and the Center for Disease Control COVID Data Tracker. These analyses includes 5,929,020 reported COVID-19 deaths in between 01/01/2020 to 06/26/2021 associated with any one of the 15 comorbidities: Influenza and Pneumonia, Diabetes, Cardiac arrest, Ischemic heart disease, Respiratory distress syndrome, Renal failure, Sepsis, Vascular and unspecified dementia, Chronic lower respiratory diseases, Heart failure, Cardiac arrhythmia, Cerebrovascular diseases, Malignant neoplasms, Obesity and Alzheimer disease. The analyses were performed using python language coding tools. Overall, the population associated with Influenza and Pneumonia infections had a significantly greater mortality (27.7% n=1,641,252) from COVID-19 followed by Diabetes (9.6%, n=568,716), Cardiac arrest (7.3%, n=431,742), Ischemic heart disease (6.6%, n=389,742), Respiratory distress syndrome (6.3%, n=372,000), Renal failure (6.1%, n=359,988), Sepsis (5.8%, n=344,082), Vascular and unspecified dementia (5.8%, n=343,410), Chronic lower respiratory diseases (5.3%, n=316,092), Heart failure (4.6%, n=273,594), Cardiac arrhythmia (4.5%, n=266,100), Cerebrovascular diseases (3.0%, n=177,684), Malignant neoplasms (2.9%, n=172,002), Obesity (2.4%, n=145,158) and Alzheimer disease (2.1%, n=127,458).

The risk of severe COVID-19 in people with Influenza and Pneumonia infections is very high compared to other comorbidities. The impact of respiratory distress syndrome and chronic lower respiratory diseases are relatively small followed by people with Cardiac, Obesity and Alzheimer disease. This shows that respiratory viral infection is the main cause of exacerbations of COVID-19 mortality. A probable hypothesis for the mechanism related to the higher risk of mortality with COVID-19 may stem from the presence of Influenza induced pro-inflammatory cytokines, impaired lung function, immunomodulatory medications that may interact with viral clearance or pathogenesis. This may lead to higher susceptibility with severe complications of COVID-19 and death. In conclusion, this study findings advice to develop strategies for the infection prevention and treatment targeting this high-risk population which might improve survival.