Mitigation of bio-corrosion characteristics of coronary artery stent by optimising fs-laser micromachining parameters.

Cardiovascular diseases, particularly coronary artery disease, pose big challenges to human life. Deployment of the stent is a preferable treatment for the above-mentioned disease. However, stents are usually made up of shape memory alloy called Nitinol. The poorer surface finish on the machined nitinol stents accelerates the migration of Nickel ions from the implanted nitinol stent, which is considered toxic and can lead to stenosis. The current study deals with controlling surface quality by minimising surface roughness and improving corrosion resistance. Femtosecond laser (fs-laser 10-15 s) micromachining was employed to machine the Nitinol surface to achieve sub-micron surface roughness. The Grey relational analysis (GRA)-coupled design of the experimental technique was implemented to determine optimal levels of four micromachining parameters (laser power, pulse frequency, scanning speed, and scanning pattern) varied at three levels to achieve minimum surface roughness and to maximise the volume ablation. The results show that to yield minimum surface roughness and maximum volume ablation, laser power and scanning speed are in a higher range. In contrast, the pulse frequency is lower, and the scanning pattern is in a zig-zag manner. ANOVA results manifest that scanning speed is the predominant factor in minimising surface roughness, followed by pulse frequency. Furthermore, the corrosion behaviour of the machined nitinol specimens was evaluated, and the results show that specimens with lower surface roughness had lower corrosion rates.

Performance assessment of vegetable-based additive enriched cutting fluid for eco-friendly machining environment.

The investigation focuses on determining the effects of canola oil-based cutting fluid with three different volume percentages of boric acid additives over the machining forces and surface roughness while turning hardened AISI 1018 mild steel. Experiments were carried out under Taguchi's design of the experiment concept. The minimum quantity lubrication (MQL) technique was followed to minimize the cutting fluid consumption. The homogeneity of the additives dispersed in the fluid has been validated through a zeta potential study. Machining forces and surface roughness were considered as chief machining objectives. The hybrid mathematical model, grey relational analysis (GRA)-artificial neural network (ANN), has been implemented to assess the performance of developed cutting fluid. The results explored that the canola oil cutting fluid with 5 wt% of boric acid additive exhibits lesser cutting forces and surface roughness. The optimal machining parameters identified by the hybrid modeling are 665 rpm of cutting speed, 35 mm/min of feed rate, and 0.3 mm of depth of cut, along with 5 wt% of boric acid composition in cutting fluid. The results explore the 2.677 times improvement in machining objective in comparison with a non-optimal set of parameters. The implementation of hybrid modeling is considered to be a novel attempt to minimize the machining objectives. It has been recorded a negligible error percentage of 0.66% between GRA and ANN prediction.

Phytochemical and in-vitro Biological Investigation of Indian Traditional Medicinal Plants for their Cytotoxicity and Hepatoprotective Potential.

OBJECTIVE: This study aimed to select 16 medicinal plants based on their folklore remedy for treating various diseases like inflammation, cancer, etc., and scientifically validate their potency. METHODS: Five among them, namely Centella asiatica (CA), Myristica fragrans (MF), Trichosanthes palmata (TP), Woodfordia fruticosa (WF), and Curculigo orchioides (CO), were scientifically confirmed through the extraction and in-vitro cytotoxic and hepatoprotective evaluation. Based on the cytotoxic and hepatoprotective results, the various fractions of CO were chosen for an in-depth phytochemical study to isolate and characterize active compounds by GC-MS. RESULTS: The results showed promising cytotoxic activity (i.e., IC50=<100 µg/ml) against HeLa cell lines and significant hepatoprotective activity in a dose-dependent manner on CCl4 intoxicated isolated hepatocyte cells. CONCLUSION: The present study confirmed the scientific evidence regarding the effectiveness of selected medicinal plants in HeLa and hepatocyte cells. Furthermore, a detailed study on their mechanism of action and clinical application is suggested.

Cellular Uptake Pathways of Nanoparticles: Process of Endocytosis and Factors Affecting their Fate.

BACKGROUND: Efficient and controlled internalization of NPs into the cells depends on their physicochemical properties and dynamics of the plasma membrane. NPs-cell interaction is a complex process that decides the fate of NPs internalization through different endocytosis pathways. OBJECTIVES: The aim of this review is to highlight the physicochemical properties of synthesized nanoparticles (NPs) and their interaction with the cellular-dynamics and pathways like phagocytosis, pinocytosis, macropinocytosis, clathrin, and caveolae-mediated endocytosis, and the involvement of effector proteins domain such as clathrin, AP2, caveolin, Arf6, Cdc42, dynamin and cell surface receptors in the endocytosis process of NPs. METHODS: An electronic search was performed to explore the focused reviews and research articles on types of endocytosis and physicochemical properties of nanoparticles and their impact on cellular internalizations. The search was limited to peer-reviewed journals in the PubMed database. RESULTS: This article discusses in detail, how different types of NPs and their physicochemical properties such as size, shape, aspect ratio, surface charge, hydrophobicity, elasticity, stiffness, corona formation, and surface functionalization change the pattern of endocytosis in the presence of different pharmacological blockers. Some external forces like a magnetic field, electric field, and ultrasound exploit the cell membrane dynamics to permeabilize them for efficient internalization with respect to fundamental principles of membrane bending and pore formation. CONCLUSION: This review will be useful to attract and guide the audience to understand the endocytosis mechanism and its pattern with respect to physicochemical properties of NPs to improve their efficacy and targeting to achieve the impactful outcome in drug-delivery and theranostic applications.

Inhibition of calculi forming oxalate by dietary Basella rubra organs: Litholytic activity

Abstract The inhibition of calculi forming oxalate by dietary Basella rubra plant organs leaf and stem pod has been investigated. The weight reduction assay was studied. Also a concoction of the plant organs was tested. Leaf extract was found with considerable activity whereas the concoction seems to be not much active as the stem pod extract. Soluble oxalate of the plant organs are partially removed prior to extraction of active constituents. The active component/s seem to be a non-protein and non-tannin molecule/s that may act through inhibition of calcium accumulation there by proving the positive activity against the calculi or kidney stone. Regular consumption of leaf and stem pod extracts of our plant would be helpful in calculi prophylaxis.

Repositioning of Drugs to Counter COVID-19 Pandemic - An Insight.

COVID-19 is a pandemic, caused by the novel coronavirus 2 (SARS-CoV-2) which is a severe acute respiratory syndrome. The devastating impact of this novel coronavirus outbreak has necessitated the need for rapid and effective antiviral therapies against SARS-CoV-2 to control the spread of the disease and importantly, alleviate the severe life-threatening symptoms and disorders. Drug repurposing strategy offers an attractive, immediate and realistic approach to tackle this growing pandemic of COVID-19. Due to the similarities with the SARS-CoV-1 virus and phylogenetic relation to the MERS-CoV virus, accelerated screening of approved drugs and the development of repositioning strategies have proved to be critical for the survival of many COVID-19 patients. Numerous scientific investigations from the initial years of the coronavirus outbreak along with upcoming advances of immunotherapy and vaccines, may prove to be beneficial. Currently, several repurposing strategies are under different phases of clinical trials and provide a definitive framework for the development of future therapies for the effective treatment of COVID-19. This review article summarizes the latest developments and trends in drug repurposing strategy for COVID-19 treatment.

Identification of (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach.

Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS-CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to identify the phytochemicals having potentials to inhibit SARS CoV-2 infection via multiple targets. The selected 132 phytochemicals were virtually screened using a structure based in silico technique against main protease (Mpro) which is a potential target of SARS CoV-2. Six compounds were selected based on the LibDock scores and further subjected to induced fit docking using the CDOCKER module of DS. Two compounds namely cinnamtannin-B and gallocatechin gallate were identified as top HITS against main protease (Mpro). Based on the Lipinski rule of five (L-ROF) and synthetic feasibility, gallocatechin gallate was taken for our further studies. Six analogues of gallocatechin gallate were screened against the next important targets such as RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE2), transmembrane protease serine -2 (TMPRSS2) and interleukin-6 (IL-6) along with main protease (Mpro). Our molecular docking results reveal that a gallocatechin analogue (GC-2) namely (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate has shown potential to inhibit multiple targets of SARS CoV-2. Further, the molecular dynamics study was carried out to ascertain the stability of the GC-2 and RdRp complex.

An effective treatment approach of DPP-IV inhibitor encapsulated polymeric nanoparticles conjugated with anti-CD-4 mAb for type 1 diabetes.

Nanotechnology based biomedical approaches and surface modification techniques made it easier for targeting specific site and improving the treatment efficacy. The present study reports on targeted polymeric nanoparticles conjugated with antibody as a site-specific carrier system for effective treatment of type 1 diabetes. Sitagliptin (SP)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) were prepared by nanoprecipitation cum solvent evaporation method and were characterized in terms of morphology, size, surface charge, and entrapment efficiency. Optimized batch demonstrated a particle size of 105.24 nm, with significant entrapment efficacy. In vitro release studies exhibited a controlled release pattern of 67.76 ± 1.30% in 24 h, and a maximum of 96.59 ± 1.26% at the end of 48 h. Thiol groups were introduced on the surface of SP-NPs whose concentration on SP-NPs was 27 ± 2.6 mmol/mol PLGA-NPs, anti-CD4 antibody clone Q4120 was conjugated to the thiolated SP-NPs via a sulfo-MBS cross-linker, ∼70% conjugation was observed. The in vitro cytotoxicity studies performed on RIN-5 F cells for mAb-SP-NPs presented an IC50 of 76 µg/mL, and the insulin release assay had revealed an increased release at 5.15 ± 0.16 IU/mL. The results indicate that mAb-SP-NPs allowed a controlled release of SP and thereby produced insulin levels comparable with control. Therefore, mAb-SP-NPs system appears to be effective in the treatment of auto immune diabetes, subject to further analysis.