Crushed Gold Shell Nanoparticles Labeled with Radioactive Iodine as a Theranostic Nanoplatform for Macrophage-Mediated Photothermal Therapy

Plasmonic nanostructure-mediated photothermal therapy(PTT) has proven to be a promising approach for cancer treatment,and new approaches for its effective delivery to tumor lesions are currently being developed.This study aimed to assess macrophage-mediated delivery of PTT using radioiodine-124-labeled gold nanoparticles with crushed gold shells(124I-Au@AuCBs) as a theranostic nanoplatform.124I-Au@AuCBs exhibited effective photothermal conversion effects both in vitro and in vivo and were efficiently taken up by macrophages without cytotoxicity.After the administration of 124I-Au@AuCB-labeled macrophages to colon tumors,intensive signals were observed at tumor lesions,and subsequent in vivo PTT with laser irradiation yielded potent antitumor effects.The results indicate the considerable potential of 124I-Au@AuCBs as novel theranostic nanomaterials and the prominent advantages of macrophage-mediated cellular therapies in treating cancer and other diseases.

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals.The primary treatment is either supportive or symptomatic.Natural products have an important role in the development of various drugs.Thus,screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses.In the current study,an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents,(e.g.,procyanidin B2,theaflavin,quercetin,ellagic acid,caffeoylquinic acid derivatives,berginin,eudesm-1β,6α,11-triol and arbutin),on the crystal structure of SARS-CoV-2 main protease(PDB ID:6w63)using AutoDock-Vina software.Many of the docked compounds revealed good binding affinity,with procyanidin B2(–8.6 Kcal/mol)and theaflavin(–8.5 Kcal/mol)showing a better or similar binding score as the ligand(–8.5 Kcal/mol).Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin.Procyanidin B2,theaflavin,and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways.Additionally,these phytoconstituents showed good ADME properties and acceptable lipophilicity,as evaluated using WLOGP.Amongst the tested compounds,procyanidin B2 showed the highest lipophilic value.It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.

Chemical Composition,Cytotoxic and Anti-arthritic Activities of Hexane Extracts of Certain Schinus Species

The genus Schinus(Anacardiaceae)comprises about 29 species that are utilized in both traditional and current medicine to alleviate various disorders such as rheumatism,bronchial infections,stomach upset,menstrual disturbance,bronchitis,and conjunctivitis.In this study we aimed to investigate the chemical composition of hexane extracts obtained from Schinus polygamous and Schinus terebinthifolius leaves as well as their cytotoxic and anti-arthritic activities.The GC-MS analysis of S.polygamus leaves revealed identification of fifty-five components:being betulin(6.54%),phytol acetate(5.27%),lupeol(3.96%),palmitic acid methyl ester(3.58%)and heptacosane(3.25%).While,seventeen compounds were identified in S.terebinthifolius leaves,predominately characterized by phytol(14.70%),lupeol(13.33%),linolenic acid methyl ester(11.17%),palmitic acid methyl ester(7.74%),and 28-oxours-12-en-3-yl acetate(7.44%).Both extracts showed moderate cytotoxic activities against hepatocellular carcinoma cells with IC_(50) values of 102.65 and 65.55μg/mL,respectively.While colorectal carcinoma cell line presented IC_(50) values of 217.78 and 83.55μg/mL,respectively.Further,both extracts provided moderate anti-arthritic effects(IC_(50):80.12 and 63.09μg/mL,respectively)using protein denaturation test,compared to diclofenac sodium(IC_(50)=15.12μg/mL).

The disruption of protein-protein interactions with co-chaperones and client substrates as a strategy towards Hsp90 inhibition

The 90-kilo Dalton(kD) heat shock protein(Hsp90) is a ubiquitous,ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates.Because many of these clients are overexpressed or become mutated during cancer progression,Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways simultaneously.The first discovered Hsp90 inhibitors,geldanamycin and radicicol,function by competitively binding to Hsp90’s N-terminal binding site and inhibiting its ATPase activity.However,most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four isoforms.Consequently,alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition,isoform-selective inhibition,and the disruption of Hsp90 protein-protein interactions.Since the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex,along with various co-chaperones and immunophilins,the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.

Enhancements of non-specific immune response in Mugil cephlus by seaweed extract against Vibrio alginolyticus(BRTR07)

Objective:To focus on the growth rate and feed utilization of fish by using trash fish feeds supplement with marine seaweeds.Methods:Selected seaweed was extracted using hot-water and its extract was mixed with trash fish feed at different concentrations(0.5%,1%and 2%for 1-30 days)and the non-specific immune response in fish was studied and challenged with Vibrio alginolyticus at 1×106 CFU/fish.The hot-water extract of seaweeds was analysed by gas chromatography-mass spectrometry.Results:The average body weight(5.320±0.018),percent weight gain(227.66±0.28),specific growth rate(2.080±0.015),hepatosomatic index(1.197±0.00)and viscerosomatic index(4.421±0.150)were significantly increased in the fish feed with seaweed containing 5%of Sargassum wightii(S.wightii)when compared with other seaweeds and control diet.Hot-water extract of S.wightii(1%)was significantly enhanced the immune response in fish when compared with other diets(0.5%and 2%).S.wightii showed good immunostimulation properties.Gas chromatography-mass spectrometry result showed that the hot-water extract of S.wightii seaweed contained fatty acids.Conclusions:Trash fish feed will reduce the production cost and also provide evidence that aqueous leaf extract of S.wightii(1%)was added to a formulated fish diet which could activate the non-specific immune response and disease resistance against Vibrio alginolyticus in Mugil cephalus.