Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

Valorization of lignocellulosic wastes for sustainable xylanase production from locally isolated Bacillus subtilis exploited for xylooligosaccharides' production with potential antimicrobial activity.

The worldwide availability of lignocellulosic wastes represents a serious environmental challenge with potential opportunities. Xylanases are crucial in lignocellulosic bio-hydrolysis, but the low enzyme productivity and stability are still challenges. In the current study, Bacillus subtilis (coded ARSE2) revealed potent xylanase activity among other local isolates. The enzyme production optimization revealed that maximum enzyme production (490.58 U/mL) was achieved with 1% xylan, 1.4% peptone, and 5% NaCl at 30 °C and pH 9. Furthermore, several lignocellulosic wastes were exploited for sustainable xylanase production, where sugarcane bagasse (16%) under solid-state fermentation and woody sawdust (2%) under submerged fermentation supported the maximum enzyme titer of about 472.03 and 485.7 U/mL, respectively. The partially purified enzyme revealed two protein bands at 42 and 30 kDa. The partially purified enzyme revealed remarkable enzyme activity and stability at 50-60 °C and pH 8-9. The enzyme also revealed significant stability toward tween-80, urea, DTT, and EDTA with Vmax and Km values of 1481.5 U/mL and 0.187 mM, respectively. Additionally, the purified xylanase was applied for xylooligosaccharides production, which revealed significant antimicrobial activity toward Staphylococcus aureus with lower activity against Escherichia coli. Hence, the locally isolated Bacillus subtilis ARSE2 could fulfill the xylanase production requirements in terms of economic production at a high titer with promising enzyme characteristics. Additionally, the resultant xylooligosaccharides revealed a promising antimicrobial potential, which paves the way for other medical applications.

Human Wharton's Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.