Abstract:In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6-1,000 µg/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were s timulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

BackgroundNanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated.MethodTQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control.ResultsThe average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of −31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration.ConclusionNLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.

In this paper we investigated the inclusion complexation between zerumbone (ZER) and hydroxylpropyl-cyclodextrin (HPCD) at four different temperatures: 293-318 •K. The thermodynamic parameters (H, S and G) for the formation of the complex were obtained from the van't Hoff equation. The complex with HPCD was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), and molecular modeling using PM6. The solubility of ZER was enhanced >30 fold after complexation. Calculations show that ZER penetrates completely into the cavity of HPCD. The complex retained its cytotoxic activity as shown by in vitro cell survival assay on human cervical cancer (Hela), breast cancer (MCF7 and MDA-MB 231) and human leukemic (CEMss) cell lines. HPCD is, therefore, a suitable encapsular capable of forming thermodynamically stable complex with ZER for save delivery of the compound as an anticancer drug in the future.

Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPβ1, leading to the prevention of nuclear localization signal (NLS) recognition. Therefore, the current study seeks to employ molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) analysis and molecular dynamics simulation studies for decrypting the binding mode, key interacting residues as well as mechanistic insights on IVM interaction with 15 potential drug targets associated with COVID-19 as well as IMPα. Among all COVID-19 targets, the non-structural protein 9 (Nsp9) exhibited the strongest affinity to IVM showing −5.30 kcal/mol and −84.85 kcal/mol binding energies estimated by AutoDock Vina and MM-GBSA, respectively. However, moderate affinity was accounted for IMPα amounting −6.9 kcal/mol and −66.04 kcal/mol. Stability of the protein-ligand complexes of Nsp9-IVM and IMPα-IVM was ascertained by 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of protein in complex with docked IVM exhibited stable root mean square deviation while root mean square fluctuations were also found to be consistent. In silico exploration of the potential targets and their interaction profile with IVM can assist experimental studies as well as designing of COVID-19 drugs. Communicated by Ramaswamy H. Sarma

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The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2 ± 29.8 nm, 0.524 ± 0.013, and −60 ± 14 mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29 cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2 , Bax , p53 , and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2 , and upregulation of Bax and p53 , with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells.

Context Colorectal cancer (CRC) is a leading cause of cancer deaths. Recently, much attention has been given to the microbiome and probiotics as preventive and therapeutic approaches to CRC and the mechanisms involved. Objectives To interpret the findings of randomized controlled trials (RCTs) of probiotics relative to patients with CRC and to outline challenges of and future directions for using probiotics in the management and prevention of CRC. Data sources Web of Science, PubMed, ProQuest, Wile, y and Scopus databases were searched systematically from January 17–20, 2020, in accordance with PRISMA guidelines. Study selection Primacy RCTs that reported the effects of administration to patients with CRC of a probiotic vs a placebo were eligible to be included. Data Extraction The studies were screened and selected independently by 2 authors on the basis of prespecified inclusion and exclusion criteria. The data extraction and risk-of-bias assessment were also performed independently by 2 authors. Results A total of 23 RCTs were eligible for inclusion. Probiotics supplementation in patients with CRC improved their quality of life, enhanced gut microbiota diversity, reduced postoperative infection complications, and inhibited pro-inflammatory cytokine production. The use of certain probiotics in patients with CRC also reduced the side effects of chemotherapy, improved the outcomes of surgery, shortened hospital stays, and decreased the risk of death. Bifidobacteria and Lactobacillus were the common probiotics used across all studies. Conclusion Probiotics have beneficial effects in patients with CRC regardless of the stage of cancer. There is an opportunity for probiotics to be used in mainstream health care as a therapy in the fight against CRC, especially in early stages; however, larger clinical trialsof selected or a cocktail of probiotics are needed to confirm the efficacy, dosage, and interactions with chemotherapeutics agents. Systematic Review Registration PROSPERO registration no. CRD42020166865.

First emerged in late December 2019, the outbreak of novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic has instigated public-health emergency around the globe. Till date there is no specific therapeutic agent for this disease and hence, the world is craving to identify potential antiviral agents against SARS-CoV-2. The main protease (M Pro ) is considered as an attractive drug target for rational drug design against SARS-CoV-2 as it is known to play a crucial role in the viral replication and transcription. Teicoplanin is a glycopeptide class of antibiotic which is regularly used for treating Gram-positive bacterial infections, has shown potential therapeutic efficacy against SARS-CoV-2 in vitro . Therefore, in this study, a mechanistic insight of intermolecular interactions between teicoplanin and SARS-CoV-2 main protease (M Pro ) has been scrutinized by molecular docking. Both monomeric and dimeric forms of M Pro was used in docking involving blind as well as defined binding site based on the known inhibitor. Binding energies of teicoplanin-M Pro complex were estimated by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) computations from docking and simulated trajectories. The dynamic and thermodynamics constraints of docked drug in complex with target proteins under specific physiological conditions was ascertained by all-atom molecular dynamics simulation of 100 ns trajectory. Root mean square deviation and fluctuation of carbon α chain justified the stability of the bound complex in biological environments. The outcomes of current study are supposed to be fruitful in rational design of antiviral drugs against SARS-CoV-2.