Multifunctional surface modifications to capture and expand flowing endothelial colony- forming cells

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Thymoquinone: a tie-breaker in SARS-CoV2-infected cancer patients?

Since the beginning of the SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) pandemic, arace to develop a vaccine has been initiated, considering the massive and rather significant economic and healthcare hits that this virus has caused. The pathophysiology occurring following COVID-19 (coronavirus disease-2019) infection has givenhints regarding the supportive and symptomatic treatments to establish for patients, as no specific anti-SARS-CoV-2 is available yet. Patient symptoms vary greatly and range from mild symptoms to severe fatal complications. Supportive treatments include antipyretics, antiviral therapies, different combinations of broad-spectrum antibiotics, hydroxychloroquine and plasma transfusion. Unfortunately, cancer patients are at higher risk of viral infection and more likely to develop serious complications due to their immunocompromised state, the fact that they are already administering multiple medications, as well as combined comorbidity compared to the general population. It may seem impossible to find a drug that possesses both potent antiviral and anticancer effects specifically against COVID-19 infection and its complications and the existing malignancy, respectively. Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings. In this review, we will discuss the multiple effects of TQ specifically against COVID-19, its beneficial effects against COVID-19 pathophysiology and multiple-organ complications, its use as an adjuvant for supportive COVID-19 therapy and cancer therapy, and finally, its anticancer effects

Scavenging the hidden impacts of non-coding RNAs in multiple sclerosis

Multiple sclerosis (MS) is a chronic neuroinflammatory disease that causes severe neurological dysfunction leading to disabilities in patients. The prevalence of the disease has been increasing gradually worldwide, and the specific etiology behind the disease is not yet fully understood. Therapies aimed against treating MS patients have been growing lately, intending to delay the disease progression and increase the patients' quality of life. Various pathways play crucial roles in developing the disease, and several therapeutic approaches have been tackling those pathways. However, these strategies have shown several side effects and inconsistent efficacy. MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) have been shown to act as key players in various disease pathogenesis and development. Several proinflammatory and anti-inflammatory miRNAs have been reported to participate in the development of MS. Hence, the review assesses the role of miRNAs, lncRNAs, and circRNAs in regulating immune cell functions better to understand their impact on the molecular mechanics of MS

High resolution C1s XPS spectra.

(A) Surfaces analyzed after the protein G polypeptide graftin step. (B) Surfaces after the antibody immobilization step using anti-CD144 antibodies.</p

ECFC capture from laminar flow conditions on functionalized surfaces.

Conditions tested include anti-C144 (present on ECFCs) on adsorbed or conjugated protein G polypeptide, anti-CD14 (not present on ECFCs) on conjugated protein G polypeptide (negative control), or collagen. (A) Fluorescence images of ECFC nuclei on modified surfaces after 1 h of exposure to cell suspension under flow conditions. (B) Quantification of number of cells per mm2 on the modified surfaces at the end of the 1 h of flow. Each symbol represents data collected using ECFCs from a separate donor. *P < 0.05 with N = 4.</p

Fluorescence-based detection of immobilized IgG antibodies on conjugated protein G polypeptide spots.

(A) Schematic representation of antibody immobilization on protein G spots with (S-SMPB(+)) or without (S-SMPB(-)) covalent grafting of protein G polypeptide. (B) Spotted anti-CD31 or anti-CD144 antibodies detected through fluorophore-labelled anti-mouse antibodies as described in the last step of Fig 1. The protein G polypeptide concentration applied was 5.5 μM. (C) Successful immobilization of different primary antibodies on conjugated protein G polypeptide (S-SMPB (+)) based on the detection of fluorophore-labeled secondary antibodies added after protein G polypeptide and primary antibody immobilization. Surfaces without S-SMPB and/or without primary antibodies were used as negative controls. *P S3 Appendix.</p

Schematic representation of the antibody immobilization process followed by a fluorescence-based antibody detection step.

Schematic representation of the antibody immobilization process followed by a fluorescence-based antibody detection step.</p

Spreadsheet comprising the raw ELISA readouts used to generate Fig 3.

(XLSX)</p

Surface atomic composition assessed by XPS survey analyses^b'*'.

Surface atomic composition assessed by XPS survey analysesb'*'.</p

DataSheet_1_Platelets’ morphology, metabolic profile, exocytosis, and heterotypic aggregation with leukocytes in relation to severity and mortality of COVID-19-patients.docx

Roles of platelets during infections surpass the classical thrombus function and are now known to modulate innate immune cells. Leukocyte-platelet aggregations and activation-induced secretome are among factors recently gaining interest but little is known about their interplay with severity and mortality during the course of SARS-Cov-2 infection. The aim of the present work is to follow platelets’ bioenergetics, redox balance, and calcium homeostasis as regulators of leukocyte-platelet interactions in a cohort of COVID-19 patients with variable clinical severity and mortality outcomes. We investigated COVID-19 infection-related changes in platelet counts, activation, morphology (by flow cytometry and electron microscopy), bioenergetics (by Seahorse analyzer), mitochondria function (by high resolution respirometry), intracellular calcium (by flow cytometry), reactive oxygen species (ROS, by flow cytometry), and leukocyte-platelet aggregates (by flow cytometry) in non-intensive care unit (ICU) hospitalized COVID-19 patients (Non-ICU, n=15), ICU-survivors of severe COVID-19 (ICU-S, n=35), non-survivors of severe COVID-19 (ICU-NS, n=60) relative to control subjects (n=31). Additionally, molecular studies were carried out to follow gene and protein expressions of mitochondrial electron transport chain complexes (ETC) in representative samples of isolated platelets from the studied groups. Our results revealed that COVID-19 infection leads to global metabolic depression especially in severe patients despite the lack of significant impacts on levels of mitochondrial ETC genes and proteins. We also report that severe patients’ platelets exhibit hyperpolarized mitochondria and significantly lowered intracellular calcium, concomitantly with increased aggregations with neutrophil. These changes were associated with increased populations of giant platelets and morphological transformations usually correlated with platelets activation and inflammatory signatures, but with impaired exocytosis. Our data suggest that hyperactive platelets with impaired exocytosis may be integral parts in the pathophysiology dictating severity and mortality in COVID-19 patients.</p