Free Inhibitor Research Articles

Antioxidant Activity of Arabian Leaves (Ziziphus spina-christi L) and Cinnamon (Cinnamomum burmannii (Nees & T. Nees) Blume) Herbal Tea

Herbal tea is a drink made from the roots, stems, flowers, leaves, seeds and fruit skin of plants which have medicinal plant benefits, easily dissolved in hot water. Herbal teas have health benefits related to the antioxidant and free radical inhibitor activity of tea which is rich in phenolic and flavonoid compounds. This study aims to determine the physical quality and antioxidant activity of herbal tea from Arabic bidara leaves and cinnamon. The method and type of research carried out is quantitative research using a descriptive design. Test parameters include physical quality tests, qualitative flavonoid tests, quantitative flavonoid tests and antioxidant activity tests using a UV-Vis Spectrophotometer. The research results from the physical quality test of chopped herbal tea have a brownish yellow color, a typical tea smell, and a typical tea bitter taste. Qualitative flavonoid tests showed that herbal tea contained flavonoid compounds in the flavonol group due to the orange color that was formed, then continued with a test to determine total flavonoid levels with results of 14.382%. The antioxidant test results on herbal tea showed an IC 50 value of 38.294 mg/L, which is included in the very strong antioxidant category.

Association of encapsulation of CDK12 inhibitor with anti-tumour activity in colon cancer cell lines.

e15077 Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Unfortunately, despite the incorporation of new therapeutic options, the metastatic setting is still an incurable disease. Cyclin-dependent kinases (CDKs) are a large family of proteins involved in cell cycle and transcriptional regulation, and are highly expressed in colon cancer, such as CDK12. Here, we explore the antitumor activity of a novel CDK12 inhibitor (CDK12-IN-E9) in preclinical models of colon cancer, and its liposomal formulation (LP-CDK12-IN-E9). Methods: Expression of CDK12 at a genomic level was assessed using web tools such as the Colonomics database. CDK12-IN-E9 was encapsulated in a liposomal formulation to evaluate differences between the free and the liposome form. The effect of compounds on cell viability was assessed with MTT assays. Matrigel assays were performed to study invasiveness and wound assays for migration. In addition, cell cycle and apoptosis studies were carried out by flow cytometry with 7-AAD, annexin V staining, and western-blot for specific protein expression. DNA damage and caspase degradation assays were performed by immunofluorescence. Results: Genomic mapping of CDK12 showed a higher expression in CRC than in normal tissue ( p−value = 1.424e−43). The CDK12 inhibitor was formulated in liposomes LP-CDK12-IN-E9 with the following characteristics: a polydispersity index of 0.11 ±0.02, a hydrodynamic radius of 62.98 ±10.29 nm and a zeta potential of -27.12±1.65 mV. CDK12-IN-E9 induced an antiproliferative effect in SW620, SW480 and HCT116 colon cancer cell lines. LP-CDK12-IN-E9 displayed an EC50 two times higher compared to CDK12-IN-E9 and a higher reduction of invasiveness between free inhibitor and its liposomal formulation mainly in HCT116 ( p-value < 0.001). Cell cycle studies showed no significant differences between CDK12-IN-E9 and LP-CDK12-IN-E9, but there was a profound induction of cell death at the highest doses through apoptosis mediated largely by caspases. In parallel to the effect on cell death, an increase in histone H2AX phosphorylation and an increase in cleaved caspase-3 was observed, which also implies a large increase in DNA damage in tumor cells. In vivo studies are ongoing. Conclusions: In summary, LP- CDK12-IN-E9 showed more antitumoral activity than its free formulation in CRC cell lines mainly through a caspase-dependent induction of apoptosis. This data suggests that liposomal formulation of novel chemical entities can augment its antitumoral properties.

Review on Medicinal Importance of Butea monosperma Lam. (Taub)

Butea monosperma is a renowned therapeutic plant, a medium size deciduous tree broadly dispersed in India, Bangladesh, Cambodia, Myanmar, China South-Central, Nepal, Laos, Sri Lanka, China Southeast, Pakistan, and Vietnam. Butea monosperma is being used in customary medication preparation from the pre historic period. It is acknowledged as the forest’s flame and is often branded as Dhak or Palash. It is described in Upanishads, Susruta Samhita, Vedas, Ashtanga Sangraha, Astanga Hridaya, and Charka Samhita. It belongs to the family of Fabaceae, which has an extensive range of vigorous principles, and it has phytoconstituents such as glycosides, flavonoids, etc.This revisional analysis is focused on the pharmacological actions, mainly shown by seeds, flowers, fruits, barks,leaves, etc., like anti-diabetic, anthelmintic, hepatoprotective, anti-stress, anti-implantation, anti-convulsant, wound healing, giardiasis, anti-oxidant, anti-dopaminergic, anti-microbial, sunscreen, anti-diarrheal, free radical scavenging, anti-filarial, anti-fungal, nephroprotective, protease inhibitor, osteogenic, hemagglutinating, anti-ulcer, giardiasis, anti-asthmatic, anti-inflammatory, anti-fertility and anti-cancer activity. GC-MS analysis of Butea monospermashows the attendance of important compounds which is volatile and HPLC analysis for non-volatile, which supplies light to its medicinal properties. These therapeutic chattels may provide impending active principles with advanced usefulness and the leastafter-effects as equated to accessible artificial drugs.

PHYTOCHEMICAL ANALYSIS AND ANTIOXIDANT ACTIVITY OF WHOLE PLANT OF TRIDAX PROCUMBENS LINN.

Antioxidants serve a critical role in preventing oxidative stress-related damage. Plants with high phenolic content havebeen shown to have antioxidant effects. The goal of this study was to look into the phytochemistry and antioxidantproperties of ethanolic extracts from Tridex procumbens (whole plant) in order to establish a statistical link betweenisolated component concentration and antioxidant capability. TLC, HPTLC, Column chromatography, and an in vitrostandard technique employing a spectrophotometer were used to assess the phytochemistry and antioxidant properties ofethanolic extractives. DPPH (l, l-diphenyl-2-piciylhydrazine) radical scavenging assay, Nitric oxide (NO) RadicalInhibition Assay, Reducing Power and hydroxyl radical scavenging assay techniques were used to assess antioxidantactivity. TLC plate with various numbers of 5 spots were implemented. The HPTLC report shows the existence of tenspots with distinct Rf values, indicating that they occupy separate areas with varying Rf values. The extracted chemicalsfrom the ethanolic extract of Tridex procumbens were column chromatographed using hexane (80ml) and benzene (20 ml)and a stationary phase silica gel. The maximum antioxidant activity was found in extracts. The Tridax procumbens extractwas the most efficient in terms of DPPH and hydroxyl radical scavenging activities, with IC50 values of 0.15, 0.12, 0.008and 42.39 g/ml, respectively. The findings show a strong link between separated chemical content and extractantioxidant capability, suggesting that Tridex procumbens might be a promising option for medicinal plant-based products asa free radical inhibitor or scavenger. However, further research is needed to ensure that it can be used effectively in bothmodern and traditional medicine.

Engineered Hybrid Nanosystem for Homologous Targeting of EMT Induced Triple Negative Breast Cancer Cells.

The increased mortality rate due to metastatic breast cancer with poor prognosis has raised concern over its effective therapy. Though various therapies and anticancer drugs have been approved, there is still a lack in the targeting of metastatic triple negative breast cancer (TNBC). We have developed a hybrid nanosystem that was synthesized by fusing exosomes from MCF-7 cells and nanovesicles from the MDA MB-231 cells that would be targeted. The developed nanosystem was characterized by various techniques like Western blotting, AFM, FETEM, DLS, CD, and fluorescence spectroscopy. The hybrid system was used for the delivery of an HDAC inhibitor, Trichostatin A (TSA), in combination with lapatinib (a tyrosine kinase inhibitor) for cotherapy of epithelial to mesenchymal transition (EMT) induced TNBC. This targeted cotherapy module had higher efficiency and effectivity in the reduction of metastatic ability and proliferation of EMT induced MDA MB-231 cells as compared to free inhibitor treatment or untargeted cotherapy. Reduction in the expression of the Wnt/β-catenin signaling pathway molecules like β-catenin (by 0.7 fold), Gsk3β (by 0.6 fold), and pGsk-3β (0.3 fold) was observed upon treatment. This subsequently resulted in the suppression of EMT markers, thereby resulting in reversing EMT to MET and suppressing metastatic breast cancer.

9 Caged rucaparib: cancer directed delivery of PARPi

Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer, improving progression free survival in the upfront and recurrent setting. Unfortunately, due to side effects patients often require dose reductions or altogether discontinue PARPi therapy. Additionally, due to bone marrow toxicity, PARPi cannot be effectively combined with chemotherapy. Recently, it was demonstrated that a ferrous iron-activated MEK inhibitor can circumvent MEKi related toxicity in non-tumorigenic tissues. Therefore, we developed a ferrous iron-activated form of rucaparib to target cancer cells while mitigating PARPi toxicity. Normal cells maintain a lower concentration of intracellular labile ferrous iron (Fe(II)) as compared with cancer cells. We introduced an Fe(II)-sensitive 1,2,4-trioxolane moiety at a reactive amine in rucaparib, creating a Fe(II)-activatable form of rucaparib (TRX-Ruc). A negative control, Di-Ruc, that cannot be activated by Fe(II), was also synthesized. Both compounds were then tested for their ability to inhibit PARP using a cell-free PARP1 assay. Cellular antiproliferative activity was tested in UWB –/– (BRCA1- deficient ovarian cancer cells) using the CellTiterGlo viability assay, and intracellular inhibition of PARP was evaluated with a parylation Western blot. In the cell free PARP1 inhibitor assay, the IC50 of rucaparib was 2.9 nM while TRX-Ruc had significantly decreased potency, with an IC50 of 92.3 nM. Di-Ruc had no inhibitory effect as expected. UWB –/– viability was decreased by rucaparib and TRX-Ruc with an equivalent IC50 of approximately 300 nM while Di-Ruc only had an effect at very high concentrations. To ensure the mechanism of TRX-Ruc on cell viability was due to PARP inhibition, a parylation western was performed. Both rucaparib and TRX-Ruc inhibited parylation while the negative control, Di-Ruc had only minimal effects. The addition of an Fe(II)-sensitive “TRX” moiety on rucaparib significantly reduces the biochemical activity of rucaparib in the absence of Fe(II). However, in an ovarian cancer cell line, the activity of TRX-ruc is restored leading to decreased cell viability, which we demonstrated was realized through the inhibition of PARP. This new Fe(II)-sensitive compound is an exciting and novel approach to deliver PAPRi specifically to cancer cells, potentially reducing toxicity and allowing effective combinations of PARPi with other cytotoxic therapies.

SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people

BackgroundSARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. ObjectivesTo investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. MethodsThis observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. ResultsNo participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count <100 × 109/L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. ConclusionIn this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination.

Abstract 10594: Cardiac Tamponade in a Covid-19 Positive Patient With Idiopathic Capillary Leak Syndrome: A Perilous Combination

Introduction: Clarkson’s disease, more known as idiopathic systemic capillary leak syndrome (SCLS) is a rare condition characterized by hypotensive episodes due to capillary hyperpermeability and can manifest as fluid accumulation in any organ or potential space. This may cause a range of complications: respiratory failure (from pulmonary edema or pleural effusion), mesenteric hypoperfusion (from hepatic congestion and severe intestinal edema), compartment syndrome and rhabdomyolysis, and even shock from hypovolemia or cardiac tamponade. Very few cases of cardiac tamponade in Clarkson's disease and COVID-19 have been reported, and when present, is certainly a serious and life-threatening complication. Case Summary: A 44-year-old female - with prior episodes of angioedema, pleural and pericardial effusions aggravated by menstruation and infection - presented with hypotension and diaphoresis. She was exposed to a COVID patient and eventually tested positive for COVID-19 infection. Persistent hypotension warranted triple inotropic support. Initial laboratories revealed hemoconcentration and hypoalbuminemia. Urinalysis was normal. 2D echocardiography showed normal left ventricular ejection fraction but with large pericardial effusion and signs of cardiac tamponade, hence, she underwent emergency pericardial windowing. She then developed pleural effusion which was drained surgically. Hepatitis, mycoplasmal and Epstein-Barr virus were negative. Direct and indirect Coomb’s test, and Lupus panel were unremarkable. Serum free light chain panel, immunopathology and C1 inhibitor results were non-diagnostic. Patient was managed as a case of idiopathic SCLS or Clarkson's disease. Methylprednisolone pulse therapy (MPPT) and intravenous immunoglobulin (IVIg) were administered. Patient was discharged with tapering doses of oral steroids and scheduled monthly IVIg infusion. Conclusions: Cardiac tamponade is a very rare but life-threatening complication of Clarkson’s disease, and on top of a COVID-19 infection, warrants emergent intervention. The pathogenesis is not yet fully elucidated. Diagnosis of SCLS is challenging thus recurrent pericardial and pleural effusions should raise the clinician’s index of suspicion.

Activated factor XI is associated with increased factor VIIa - Antithrombin complexes in stable coronary artery disease: Impact on cardiovascular outcomes.

Coronary artery disease (CAD) is associated with a prothrombotic tendency including increased factor (F) VIIa-antithrombin (FVIIa-AT) complexes, a measure of tissue factor (TF) exposure, and activated FXI (FXIa). We investigated whether increased FVIIa-AT complexes are associated with FXIa and active TF and if major adverse clinical outcomes are predicted by the complexes in CAD. In 120 CAD patients, we assessed FVIIa-AT complex concentrations and the presence of circulating FXIa and active TF. Levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), interleukin-6, high-sensitivity C reactive protein, prothrombin fragment 1 + 2, and free Tissue Factor Pathway Inhibitor were determined. Myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SE), and cardiovascular (CV) death were recorded separately and as a composite endpoint, during follow-up. FVIIa-AT complexes were positively associated with current smoking and multivessel CAD. Elevated FVIIa-AT complexes characterized patients with circulating FXIa and/or active TF in association with increased plasma isoprostanes but not with thrombin generation or inflammatory markers. During a median follow-up of 106 months (interquartile range 95-119), high baseline levels of FVIIa-AT complexes predicted ischemic stroke/SE (HR 4.61 [95% CI 1.48-18.42]) and a composite endpoint of MI, stroke/SE, and CV death (HR 7.47 [95% CI 2.81-19.87]). This study is the first to show that high FVIIa-AT complexes characterize advanced CAD patients with detectable FXIa and active TF, which is, in part, driven by oxidative stress. High FVIIa-AT complexes were associated with the risk of ischemic stroke/SE during long-term follow-up, highlighting the need for effective antithrombotic agents in CAD.

Acrylate‐free tough 3D printable thiol‐ene thermosets and composites for biomedical applications

AbstractPolymer thermosets and composites based on rigid trizaine‐trione (TATO) alkene and thiol monomers show great promise as bone fixation materials and dental composites due to their ability to efficiently crosslink via thiol‐ene coupling chemistry into stiff and strong materials. In order to broaden the scope of these materials, a TATO thermoset was optimized for sterolithography (SLA) 3D printing through the addition of either a diluent (PETMP) and photo‐absorber (Sudan I), or the addition of a free radical inhibitor (pyrogallol). A 3D printable hydroxyapatite (HA) composite was also formulated by adding a combination of nano‐HA and micro‐HA particles, which were found to increase the thermal stability and modulus of the material, respectively. The modulus of the printed thermosets containing Sudan I and pyrogallol exceeded any previously published acrylate‐free thiol‐ene SLA resins, at 1.6 (0.1) and 1.85 (0.06) GPa, respectively. The printed HA composite formulation had a modulus of 2.4 (0.2) GPa. All three formulations showed a comparable resolution to a commercially available SLA resin and were non‐toxic toward Raw 264.7 and human dermal fibroblast cells. These results demonstrate the potential of TATO based SLA resins for the construction of strong, fully‐customizable, printed implants for biomedical applications.

Construction of macromolecule cross-linked anion exchange membranes containing free radical inhibitor groups for superior chemical stability

In order to achieve high chemical stability of anion exchange membranes (AEMs), polystyrene (PVE) containing free radical inhibitor groups is first used to cross-link fluorinated poly(aryl ether ketone) (PAEK). The crosslinked PAEK is afterwards quaternized with 6-bromohexyltrimethylammonium bromide (QA) to fabricate AEMs. The prepared AEMs show obvious microphase separation with anionic cluster spacing within 8.8–9.3 nm according to the SAXS analysis results. The hydroxide conductivity of the proposed AEMs is in the range of 76.7–97.6 mS cm−1 at 80 °C. It is found that the free radical inhibitor groups as well as the dense cross-linked structure endow the AEMs with excellent resistance against the attack of OH‾ and free radicals. After immersed in 1 mol L−1 KOH at 60 °C for 1000 h, the QPAEK-30PVE membrane exhibits about 75% and 82% of the conductivity and IEC retention rate. Using this membrane as the electrolyte, a peak power density of 329 mW cm−2 is achieved under a cell voltage of 0.66 V at 60 °C by fueling the cell with humidified H2 and O2 without back pressure.

Nutritional prospective of Sesbania species: an underutilized wild legume from Northern Western Ghats, Maharashtra, India

Nutrition plays very important role in longevity of life. Processed food has created various health disorders at a very alarming rate. Wild genotypes have potent nutritive characteristics which are relatively less explored. In the current investigation, two species of Sesbania were evaluated for their potent nutritional value. Sesbania grandiflora and Sesbania bispinosa seeds contained 37.78% and 30.2% crude proteins, 4.24% and 2.06% albumins, 7.20% and 5.16% globulins, 1.75% and 8.34% free amino acids, 34.91% and 59.08% total carbohydrates and 5.2% and 5.02% total lipids respectively. DPPH Radical scavenging assay revealed notable antioxidant potential with 62.27% and 65.45% inhibition respectively. Antinutrient analysis indicated the presence of total free phenols (0.29% and 0.63%), tannins (0.28% and 0.34%), phytic acid (1.70% and 1.59%) and trypsin inhibitor activity (41.8 and 54.4 TIU/mg) respectively. Both Sesbania species had excellent nutritional potential as well as antioxidant activity and a low antinutrient profile. Based on the findings, Sesbania species may be investigated further as a potential alternative food source in the near future, particularly in economically disadvantaged areas, and may pave the way toward the wider aim of food security.

High-performance thin-layer chromatography coupled attenuated total reflectance-Fourier-transform infrared and NMR spectroscopy-based identification of α-amylase inhibitor from the aerial part of Asparagus racemosus Willd.

α-Amylase inhibitors from natural sources are of interest for new drug development for the treatment of diabetes mellitus (DM). High-performance thin-layer chromatography (HPTLC) coupled bioassay guided isolation of bioactive compounds has been improved within last few years. A microchemical derivatised HPTLC-coupled attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopy was employed for profiling α-amylase inhibitor from the aerial part of Asparagus racemosus Willd. Asparagus racemosus Willd. aerial part extracted with different solvents (n-hexane, chloroform, ethyl acetate, and methanol) and assayed to detect free radical scavengers and α-amylase inhibitor by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and starch-iodine assay method, respectively. HPTLC-coupled ATR-FTIR and NMR spectroscopy was used to identify the α-amylase inhibitor. Methanolic extract of A. racemosus showed highest antioxidant activity (21.99 μg GAE/μL) where n-hexane extract showed lowest antioxidant activity (5.87 μg GAE/μL). The α-amylase inhibition was recorded as highest and lowest in ethyl acetate extract (13.13 AE/μL) and n-hexane extract (3.92 AE/μL), respectively. The deep blue zone of α-amylase sprayed TLC plate of extracts with hRF = 72 analysed for ATR-FTIR and NMR spectroscopy which revealed the presence of stigmasterol is responsible for α-amylase inhibition. The present work establishes the α-amylase inhibiting properties of A. racemosus maintaining its use for the treatment of DM as a traditional medicine. Bioassay guided isolation through HPTLC-coupled ATR-FTIR and NMR spectroscopy offers an effective method for the exploration of bioactive compounds such as α-amylase inhibitor from complex plant extracts.

EFFECT OF YEAST TYPE ON ANTIOXIDANT ACTIVITY AND PHENOLIC CONTENT IN FERMENTED TALIPUK SEED FLOUR

Talipuk seed flour is processed from mature talipuk seeds. This flour is commonly used as a raw material for traditional cakes and as a substitute for wheat flour by the people of South Kalimantan. Talipuk seeds contain various compounds that function well for health. However, talipuk seeds are less desirable because they have a sandy texture and contain anti-nutritional compounds that cause a less desirable flavor. This can be overcome by fermentation by yeast. This study was conducted to analyze the functional properties (total phenolic content by the Folin-Ciocalteau method and antioxidant activity with the free radical inhibitor DPPH (2,2-diphenyl-1-picrylhydrazil) in talipuk seed flour fermented with various yeasts. Talipuk seeds were fermented by fermentation spontaneously, tape yeast, baker's yeast and tempeh yeast for 48 hours. The results of the fermentation are dried using an oven at 60oC for 8 hours or with a hot sun for ± 12 hours. Then mashed and sieved with a 60 mesh flour sieve to obtain fermented talipuk seed flour Based on the results of research, the fermentation of talipuk seed flour can increase the total phenolic content and antioxidant activity of talipuk seed flour. The highest total phenolic in the fermentation of talipuk seed flour using baker's yeast is 61.22 mg/g GAE and tape yeast 56.40 mg/g GAE, while the highest antioxidant activity in unfermented talipuk bij flour was 84.85%, followed by fermentation of talipuk seed flour using 47.34% baker's yeast and 36.34 % tape yeast. The use of baker's yeast and tape yeast in the fermentation of talipuk seed flour gave better total phenolic and antioxidant activity test results than spontaneous fermentation and fermentation using tempeh yeast.

Phytochemical Analysis and Antioxidant Activity of Avocado Pear Peel (Persea americana) Extract

This study evaluated the phytochemicals and antioxidant activity in Persea americana peel it also assessed the efficiency of Persea americana peel (Avocado Pear fruit peel) waste in different in vitro activities in order to explore the possibility of utilizing waste as a value-added product in various applications.. Quantitative phytochemical analysis was performed. Quantitative phytochemical screening confirmed the presence of alkaloids (56.5063 ug/ml), flavonoids (245.6875 ug/ml), phenols (15.65 ug/ml), tannins (27.03 ug/ml) phytate (9.68 ug/ml), oxalate (13.65%), saponin (22.73 ug/ml). For antioxidant activity, the peels of fruit sample of Persea americana were prepared in ethanol solution. The vitamin content of the peel extract was assayed using calorimetric and titration methods while the antioxidant enzyme assay was determined by spectrophotometric method. The antioxidant enzyme assay was also determined for catalase, Superoxide dismutase (SOD) and glutathione peroxidase. The Vitamins A, C and E were found to be present, with Vitamin A being the highest in concentration. Copper, Zinc, Iron and manganese were also present in the peel extract. The result from this study indicates that the peel extract of Persea americana possess antioxidant properties and could serve as free radical scavenger or inhibitor.

Incorporation of a Coumarate Based Corrosion Inhibitor in Waterborne Polymeric Binders for Corrosion Protection Applications

AbstractThe incorporation of organic corrosion inhibitors into waterborne coatings is optimized in this work. Herein, p‐coumaric acid (4‐hydroxycinnamic acid) is modified by a butyl radical and its effectiveness as an anticorrosive free inhibitor in solution is confirmed by potentiodynamic polarization (PP). The molecule is then successfully incorporated into waterborne polymeric binders by employing different polymerization techniques in dispersed media. Whenever possible, the inhibitor is also blended into the bare latexes to compare the effect of the incorporating method. The anticorrosion performance of the obtained coatings is tested and compared by electrochemical analysis. Promising results are obtained for the coatings produced by semibatch emulsion polymerization even at the low concentration of 1.5 mg of inhibitor g−1 latex. The intact control coating without inhibitor shows an impedance of up to 106 Ω and a phase angle of 72° after 1 h of immersion in the corrosive medium, meanwhile the coating with inhibitor shows higher values, 106.7 Ω and 80°. Active corrosion inhibition is observed in the coating with inhibitor in which a defect has been done, as the impedances drop to 103.9 Ω after 24 h of immersion in the saline solution while in the control scratched coating it drops to 103.6 Ω.

Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.

Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity

Background:MiR-196a is particularly noticeable in the development of liver cancer. However, the rapid degradation by ribonuclease (RNase) imposes a limit on the miRNA gene therapy applications.Aims:To design a novel gene-targeting nano system for liver cancer treatment.Study Design:Cell culture study and animal experimentation.Methods:Deacetylated (DEAC)-poly-N-acetylglucosamine (PNAG)-folic acid (FA) was prepared via ethyl (dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction, and miR-196a inhibitor (miR-196a I)/DEAC-PNAG-FA was prepared through self-assembly. The characterization and nucleic acid protection of the self-assembly system were also determined. The biological function and related mechanism of the prepared system were studied at cellular and molecular levels. Mice were established as a xenotransplantation model to evaluate the anticancer capacity of miR-196a I/DEAC-PNAG-FA in vivo.Results:The morphology of miR-196a I/DEAC-PNAG-FA was uniform, and its particle size was approximately 70–100 nm. A nanocarrier with an N/P ratio of 200:1 can maximize the nucleic acid carrying capacity of the self-assembly system. The nanosystem can protect miRNA from RNase degradation and could be internalized rapidly within 4 h. The self-assembly system significantly enhanced the apoptosis-inducing effect of miR-196a I on HepG2 cells (P = 0.003). Molecular biological analyses confirmed that the apoptosis-inducing effect of the nanosystem was due to the inhibition of miR-196a gene expression in HepG2 cells, which upregulate the expression of pro-apoptotic proteins FOXO1 (P < 0.001), Bax (P < 0.001), Ki67 (P < 0.001), and proliferating cell nuclear antigen (P < 0.001), and inhibit the expression of apoptosis inhibitory protein Bcl-2 (P < 0.001). Moreover, compared with free miR-196a inhibitor or miR-196a I/DEAC-PNAG, miR-196a I/DEAC-PNAG-FA can more effectively inhibit tumor growth in vivo (P = 0.026).Conclusion:The newly prepared self-assembly targeting system can effectively induce apoptosis and abrogate tumor growth, which may open a new approach for liver cancer treatment.

Assesment of free radical scavenging activity and inhibitory properties of aqueous extract of Cymodocea serrulata segrass towards α- glucosidase and α –amylase enzyme

Aim: The study reports the in vitro free radical scavenging and α-amylase and α-glucosidase inhibition activities of aqueous extract of seagrass Cymodocea serrulata from Gulf of Mannar, Southeast Asia. Methods: The free radical scavenging activity was evaluated by DPPH, Superoxide, Nitric oxide and Hydroxyl radical scavenging assays and α-amylase, α-glucosidase enzyme inhibitory activity. The C. serrulata showed effective DPPH radical scavenging activity of 69.45 μg/mL, Superoxide radical scavenging activity of 91.08.5 ± 0.02%, Nitric oxide radical scavenging activity of 86.89 ± 0.03% and Hydroxyl radical scavenging activity of 81.09 ± 0.3 % at a concentration of 5 μg/mL respectively. It also showed significant inhibitory activity against α- amylase with an IC50 value of 3.0 ± 0.04 (μg/ml) and the α-glucosidase inhibitory activity with an IC50 value of 3.7 ± 1.01 (μg/ml) at concentrations of 1-5 μg/mL. Conclusion: Cymodocea serrulata was found to be a potent free radical scavenger and inhibitor of α-amylase and α-glucosidase enzymes.