Chitosan-encapsulated naringenin promotes ROS mediated through the activation of executioner caspase-3.

We previously reported that chitosan nanoparticle-encapsulated Naringenin (CS-NPs/NAR) could scavenge free radicals at lower doses and be cytotoxic to cancer cells. The current study continues to focus on the mechanism behind CS-NPs/NAR-induced breast cancer cell (MDA-MB-231) death. MDA-MB-231 cells were treated with higher concentrations (100, 200, and 200 µg) of Chitosan nanoparticles (CS-NPs), naringenin (NAR), and chitosan-encapsulated naringenin (CS-NPs/NAR). The cell viability, proliferation, and oxidative stress parameters, such as nitric oxide [NO], xanthine oxidase (XOD), and xanthine dehydrogenase (XDH) levels, were analyzed. ROS levels were determined through DCFDA analysis. MTT-based cell cytotoxicity and BrdU cell proliferation analysis depicted the cytotoxicity effects (37% and 29% for 24 and 48 h) and exhibited a reduction in the proliferation of MDA-MB-231 by CS-NPs/NAR. A significant increase in NO content, XOD, a decrease in XDH, and an increase in ROS levels were observed upon treatment with CS-NPs/NAR. Fluorescent images suggested the increase in the ROS level upon treatment with CS-NPs/NAR in cancer cells, and the results suggested that it could induce apoptosis. Further, to confirm this, the activity of caspase-3 was analyzed through western blotting, and the result suggested that the higher concentration of CS-NPs/NAR has increased the activation of procaspase3 when compared to free NAR. Hence, the current investigation concludes that high doses of CS-NPs/NAR induce and increase oxidative stress and so increased activation of procaspase3 may lead to cancer cell apoptosis and reduction in cell proliferation.

Antiviral properties of copper and its alloys to inactivate covid-19 virus: a review.

Copper (Cu) and its alloys are prospective materials in fighting covid-19 virus and several microbial pandemics, due to its excellent antiviral as well as antimicrobial properties. Even though many studies have proved that copper and its alloys exhibit antiviral properties, this research arena requires further research attention. Several studies conducted on copper and its alloys have proven that copper-based alloys possess excellent potential in controlling the spread of infectious diseases. Moreover, recent studies indicate that these alloys can effectively inactivate the covid-19 virus. In view of this, the present article reviews the importance of copper and its alloys in reducing the spread and infection of covid-19, which is a global pandemic. The electronic databases such as ScienceDirect, Web of Science and PubMed were searched for identifying relevant studies in the present review article. The review starts with a brief description on the history of copper usage in medicine followed by the effect of copper content in human body and antiviral mechanisms of copper against covid-19. The subsequent sections describe the distinctive copper based material systems such as alloys, nanomaterials and coating technologies in combating the spread of covid-19. Overall, copper based materials can be propitiously used as part of preventive and therapeutic strategies in the fight against covid-19 virus.

Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells.

Endoplasmic reticulum (ER) plays a key role in the folding, modification, and trafficking of proteins. When the homeostasis of the ER is disturbed, un/misfolded proteins accumulate in the ER which leads to ER stress. Sustained ER stress results in apoptosis, which is associated with various diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor in redox homeostasis by regulating various genes associated with detoxification and cell-protective mechanisms. We found that Rosolic acid (RA) treatment dose-dependently activates Nrf2 in endothelial cells using the enzyme fragment complementation assay. The cytoprotective role of RA against ER stress-induced endothelial apoptosis and its molecular mechanism was explored in the present study. The Nrf2 and its target genes, as well as ER stress marker expressions, were measured by qPCR in ER stress-exposed endothelial cells. The contribution of Nrf2 in RA-mediated defense mechanism in endothelial cells was established by knockout studies using Nrf2-CRISPR/Cas9. The treatment with RA to ER stress-induced endothelial cells exhibited activation of Nrf2, as demonstrated by Nrf2 translocation and reduction of ER stress markers. We found that the Nrf2 knockout sensitized the endothelial cells against ER stress, and further, RA failed to mediate its cytoprotective effect. Proteomic studies using LC-MS/MS revealed that among the 1370 proteins detected, we found 296 differentially regulated proteins in ER stress-induced endothelial cells, and RA administration ameliorated 71 proteins towards the control levels. Of note, the ER stress in endothelial cells was attenuated by the treatment with the RA, suggesting the role of the Nrf2 activator in the pathological conditions of ER stress-associated diseases.

Multilayer capsules encapsulating nimbin and doxorubicin for cancer chemo-photothermal therapy.

Layer-by-layer (LbL) assembled poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) microcapsules were designed to incorporate gold nanorods (NRs) and co-encapsulate and release two drugs for cancer therapy. Calcium carbonate (CaCO3) microparticles modified with preformed NRs were used as sacrificial templates for the fabrication of hollow PAH/PMA/NR capsules incorporated with NRs. The hollow capsules were found to be 4.5 ± 0.5 µm in size and appeared with uniformly distributed NRs in the interior of the capsules. The morphology of the capsules transformed from pore free continuous structure to porous structure under laser light irradiation at 808 nm and 0.5 W cm-2. The encapsulation experiments showed that the hydrophilic drug (doxorubicin hydrochloride, Dox) was encapsulated in the interior of the capsules while the hydrophobic drug (nimbin, NB) was entrapped in the porous polymeric network of the layer components. The encapsulation efficiency was found to be 30% for both Dox and NB. The release experiments showed an initial burst release followed by sustained release up to 3 h. Notably, the release was completed within 30 min under NIR irradiation at 808 nm. The estimated IC50 values against THP-1 cells were 75 and 1.8 µM for NB and Dox, respectively. The dual drug loaded capsules showed excellent anticancer activity against THP-1 cells under NIR light exposure in in-vitro experiments. Thus, such remotely addressable dual-drug loaded capsules with the provision for encapsulation of natural drugs demonstrate high potential for use as theranostics in cancer therapy.

Cytotoxic effects of Aeromonas hydrophila culture supernatant on peripheral blood leukocytes of Nile tilapia (Oreochromis niloticus): Possible presence of a secreted cytotoxic lectin.

Number of exotoxins like haemolysin, leukocidin, aerolysin etc. were reported from Aeromonas hydrophila. In this study, we report the haemolytic and cytotoxic effect of A. hydrophila culture supernatant (CS) that is specifically inhibited by lactose and also by serum and mucus of Nile tilapia (Oreochromis niloticus). Hence, we assume the presence of a secreted lectin in the CS. CS is toxic to peripheral blood leukocytes (PBL) of O. niloticus as revealed by MTT assay and by flow cytometry. DNA laddering assay indicates that CS causes necrosis to PBL. As a result of necrosis, CS treated PBL showed increased production of reactive oxygen species as indicated by nitroblue tetrazolium and 2',7' -dichlorofluorescin diacetate assays. CS treated PBL showed reduced mRNA expression of TNF-α and IFN-γ genes. When CS was subjected to polyacrylamide gel electrophoresis, it showed a single band corresponding to the molecular weight of 45 kDa. However, upon concentrating the CS by ultrafiltration, many bands were visualized. Further studies at molecular level are required to unravel this macromolecular-leukocyte interaction which would ultimately benefit the aquaculture industry.

Evaluation of Endothelial and Platelet Derived Microparticles in Patients with Acute Coronary Syndrome.

BACKGROUND: Microparticles (MP) are a nuclear fragments of membrane released by the damaged cell during stress. Elevated levels of MP have been found in patients with acute coronary syndrome (ACS) owing to the damage in the endothelium. AIM: To determine if the levels of endothelial and platelet microparticles (EMP & PMP) in patients with ACS influenced the severity of the disease. MATERIALS AND METHODS: This was a prospective cohort study performed in 63 ACS patients (ST elevation myocardial infarction- STEMI-28, non ST elevation myocardial infarction -NSTEMI-35). After obtaining consent, blood samples were collected from the patients and processed by flow cytometry. RESULTS: The NSTEMI group had higher levels of EMP {792.11(327.59-1661.49) vs 300.35 (176.3-550.46), p=0.001} and PMP {218.87(86.65-439.77) vs 114.45(50.34-196.75), p= 0.007} as compared to the STEMI group. However, it was found that the EMP (r=-0.438, p=0.001) and PMP (r= -0.316, p=0.024) negatively correlated with Global Registry of Acute Coronary Events score (GRACE in-hospital score) for the entire cohort. CONCLUSION: The levels of microparticles are elevated in ACS patients and may reflect a protective effect in patients with acute coronary syndrome.

In vitro evaluation of antibacterial efficacy of calcium hydroxide in different vehicles.

AIM: This study was aimed to evaluate the antibacterial effect of calcium hydroxide (CH) in different vehicles in an in vitro model. MATERIALS AND METHODS: Calcium hydroxide paste prepared with two conventionally used vehicles namely, camphorated monochlophenol, distilled water and propylene glycol. The antibacterial activity of these paste were tested against five micro-organisms that can commonly occur in the infected root canals. RESULTS: The results of this study indicate that a paste of CH made with propylene glycol exerts significant antibacterial action. Hence, it can be recommended for use as an intracanal medicament in preference to a paste prepared with a tissue toxic phenolic compound like camphorated monochlorophenol.

Antifeedant neo-clerodanes from Teucrium tomentosum Heyne. (Labiatae).

From the acetone extract of Teucrium tomentosum, a new antifeedant neo-clerodane diterpenoid teuctosin (1) was isolated along with teuflin (2), teucrin-H(2) (3), 6beta-hydroxyteuscordin (4), 6beta-acetylteuscordin (5) and montanin-D (6). The structure of the new compound was elucidated comprehensively using 1D and 2D NMR methods and confirmed by X-ray crystallography. All the compounds showed effective antifeedancy against Plutella xylostella and Spodoptera litura at 10 mug/cm(2) of leaf area.

Zaluzanin D: a fungistatic sesquiterpene from Vernonia arborea.

Zaluzanin D, a sesquiterpene lactone has been isolated from the aerial parts of Vernonia arborea as a major constituent (0.04%). Antifungal activity of zaluzanin D has been studied against six plant-pathogenic fungi.

Antifeedant and growth inhibitory effects of some neo-clerodane diterpenoids isolated from Clerodendron species (Verbenaceae) on Earias vitella and Spodoptera litura.

Antifeedant and growth inhibitory effects of various neo-clerodane diterpenoids having a furofuran moiety, isolated from Clerodendron spp., were studied using Earias vitella and Spodoptera litura. The compounds clerodendrin B, 3-epicaryoptin, 15-hydroxyepicaryoptin, and clerodin were effective antifeedants at 10 microg/cm(3) (30 microg/g) of diet against E. vitella and at 10 microg/cm(2) of leaf against S. litura. All of the tested compounds, namely, clerodendrin B, 3-epicaryoptin, clerodendrin C, 15-hydroxyepicaryoptin, clerodendrin B acetate, and clerodin, showed good insect growth inhibitory activity even at lower concentrations.

Microbial transformation of zaluzanin-D.

Microbial transformation of zaluzanin-D using different fungi gave 11,13-dihydrozaluzanin-C, zaluzanin-C, 4,16,11,13 - tetrahydro zaluzanin-C, estafiatone, dihydroestafiatol and dihydroestafiatone.