Robust thrombolytic and anti-inflammatory action of a constitutively active ADAMTS13 variant in murine stroke models.

Advances in our understanding of ADAMTS13 structure, and the conformation changes required for full activity, have rejuvenated the possibility of its use as a thrombolytic therapy. We have tested a novel Ala1144Val ADAMTS13 variant (constitutively active [ca] ADAMTS13) that exhibits constitutive activity, characterized using in vitro assays of ADAMTS13 activity, and greatly enhanced thrombolytic activity in 2 murine models of ischemic stroke, the distal FeCl3 middle cerebral artery occlusion (MCAo) model and transient middle cerebral artery occlusion (tMCAO) with systemic inflammation and ischemia/reperfusion injury. The primary measure of efficacy in both models was restoration of regional cerebral blood flow (rCBF) to the MCA territory, which was determined using laser speckle contrast imaging. The caADAMTS13 variant exhibited a constitutively active conformation and a fivefold enhanced activity against fluorescence resonance energy transfer substrate von Willebrand factor 73 (FRETS-VWF73) compared with wild-type (wt) ADAMTS13. Moreover, caADAMTS13 inhibited VWF-mediated platelet capture at subphysiological concentrations and enhanced t-PA/plasmin lysis of fibrin(ogen), neither of which were observed with wtADAMTS13. Significant restoration of rCBF and reduced lesion volume was observed in animals treated with caADAMTS13. When administered 1 hour after FeCl3 MCAo, the caADAMTS13 variant significantly reduced residual VWF and fibrin deposits in the MCA, platelet aggregate formation, and neutrophil recruitment. When administered 4 hours after reperfusion in the tMCAo model, the caADAMTS13 variant induced a significant dissolution of platelet aggregates and a reduction in the resulting tissue hypoperfusion. The caADAMTS13 variant represents a potentially viable therapeutic option for the treatment of acute ischemic stroke, among other thrombotic indications, due to its enhanced in vitro and in vivo activities that result from its constitutively active conformation.

Nutritional Significance, Antimicrobial, Antioxidants, Anticancer, and Antiviral Activities of Lemongrass Leaves Extract and Its Application as Hepatoprotective Agent against CCl4-Induced Hepatic Injury in Rats.

This work investigated the antioxidant and hepatoprotective activities of lemongrass extract and its effects on rat hepatotoxicity. The lemongrass extract (LGE) contains bioactive components such as phenolic acids, flavonoid components, vitamin C, fibers, and tannins. The LGE had high phenolic content (397 mg/100g) and flavonoids (164 mg/100g), influencing its antioxidant activity of 91.25%. Additionally, it inhibited 81% of breast cancer, also, inhibited the growth of pathogenic bacteria and Candida at a concentration of 20-40 µg/mL. Additionally, it inhibited SARS-Cov-2 by 75%; however, increasing the activity of Cas-3. Quercetin-3-rhamnoside was the main phenolic compound in the HPLC profile; the phenolic compounds may be attributable to the beneficial effects of LGE. In this study, the CCl4-challenged rats delivered two levels of LGE (100 and 300 mg/kg BW). LGE reduced ALT, AST, creatinine and urea by 50 and 37%, respectively. Generally, LGE mitigated the oxidative stress induced by CCl4, which is evident in the histology of liver and kidney tissues, where significant improvement, with no cytoplasmic degradation in undamaged liver hepatocytes, improved kidney performance and shape. It can be concluded that polyphenolic-rich LGE can mitigate the oxidative stress induced by CCl4 and other parameters while enhancing kidney and liver performance.

Characterization of Portulaca oleracea Whole Plant: Evaluating Antioxidant, Anticancer, Antibacterial, and Antiviral Activities and Application as Quality Enhancer in Yogurt.

Purslane (Portulaca oleracea L.) is rich in phenolic compounds, protein, and iron. This study aims to produce functional yogurt with enhanced antioxidant, anticancer, antiviral, and antimicrobial properties by including safe purslane extract in yogurt formulation; the yogurt was preserved for 30 days at 4 °C, and then biochemical fluctuations were monitored. The purslane extract (PuE) had high phenolic compounds and flavonoids of 250 and 56 mg/mL, respectively. Therefore, PuE had considerable antioxidant activity, which scavenged 93% of DPPH˙, inhibited the viability of MCF-7, HCT, and HeLa cell lines by 84, 82, and 80%, respectively, and inhibited 82% of the interaction between the binding between Spike and ACE2 compared to a SARS-CoV-2 inhibitor test kit. PuE (20-40 µg/mL) inhibited the growth of tested pathogenic bacteria and Candida strains, these strains isolated from spoild yogurt and identified at gene level by PCR. Caffeic acid glucoside and catechin were the main phenolic compounds in the HPLC profile, while the main flavor compound was carvone and limonene, representing 71% of total volatile compounds (VOCs). PuE was added to rats' diets at three levels (50, 150, and 250 µg/g) compared to butylated hydroxyanisole (BHA). The body weight of the rats fed the PuE diet (250 µg/g) increased 13% more than the control. Dietary PuE in rats' diets lowered the levels of low-density lipoprotein (LDL) levels by 72% and increased the levels of high-density lipoprotein (HDL) by 36%. Additionally, liver parameters in rats fed PuE (150 µg/g) decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels by 50, 43, and 25%, respectively, while TP, TA, and GSH were increased by 20, 50, and 40%, respectively, compared to BHA. Additionally, PuE acts as a kidney protector by lowering creatinine and urea. PuE was added to yogurt at three concentrations (50, 150, and 250 µg/g) and preserved for 30 days compared to the control. The yogurt's pH reduced during storage while acidity, TSS, and fat content increased. Adding PuE increased the yogurt's water-holding capacity, so syneresis decreased and viscosity increased, which was attributed to enhancing the texture properties (firmness, consistency, and adhesiveness). MDA decreased in PuE yogurt because of the antioxidant properties gained by PuE. Additionally, color parameters L and b were enhanced by PuE additions and sensorial traits, i.e., color, flavor, sugary taste, and texture were enhanced by purslane extract compared to the control yogurt. Concerning the microbial content in the yogurt, the lactic acid bacteria (LAB) count was maintained as a control. Adding PuE at concentrations of 50, 150, and 250 µg/g to the yogurt formulation can enhance the quality of yogurt.

The influence of dietary supplementation with fermented agro-industrial residue of faba bean on Japanese quail performance, immunity, gut microbiota, blood chemistry, and antioxidant status.

Antibiotic overuse in poultry feeds has disastrous implications; consequently, long-term alternatives must be developed. As a result, the current study aims to assess the impact of Aspergillus niger filtrate (ANF) high in organic acids grown on agro-industrial residue of faba bean (AIRFB) on quail diet, as well as their influence on bird productivity, digestion, carcass yield, blood chemistry, and intestinal microbiota. A total of 240 Japanese quails (aged 7 d) were used in this study, divided equally among 5 experimental groups with 48 quails each. Group 1 (G1) received a basal diet without any ANF, group 2 (G2) received a basal diet supplemented with 0.5 mL ANF/kg diet, group 3 (G3) received a basal diet supplemented with 1.0 mL ANF/kg diet, group 4 (G4) received a basal diet supplemented with 1.5 mL ANF/kg diet, and group 5 (G5) received a basal diet supplemented with 2 mL ANF/kg diet. The performance parameters were monitored at 1 to 3, 3 to 5, and 1 to 5 wk. Adding ANF increased body weight at 3 and 5 wk, as well as body weight gain at 1 to 3, 3 to 5, and 1 to 5 wk, compared to the control diet. The ANF fed quails had the highest feed conversion ratio compared to the control group. The addition of ANF to the quail diet had no effect on the weight of the carcass, gizzard, heart, liver, giblets, or dressing; however, it did lower triglycerides, low-density lipoprotein, and very low-density lipoprotein while increasing high-density lipoprotein levels. The quail groups that received ANF had enhanced immunological indices such as IgG, IgM, IgA, and lysozymes. It also increased the levels of superoxide dismutase and total antioxidant contents, as well as catalase, and digestive enzymes such as protease, amylase, and lipase. However, it lowered the blood MDA levels compared to control. It has been demonstrated that the total gut microbiota, Escherichia coli, total coliforms, and the population of Salmonella are all reduced in ANF-fed quails. Histological examination of ANF quails' liver and intestinal sections revealed normal hepatic parenchyma, typical leaf-like intestinal villi, and comparatively short and frequently free lumina. In conclusion, Japanese quail showed improvements in performance, digestive enzymes, antioxidant indices, immunity, and capacity to reduce intestinal pathogenic bacteria after consuming diet supplemented with ANF.