Application of Digital Holographic Imaging to Monitor Real-Time Cardiomyocyte Hypertrophy Dynamics in Response to Norepinephrine Stimulation.

Cardiomyocyte hypertrophy, characterized by an increase in cell size, is associated with various cardiovascular diseases driven by factors including hypertension, myocardial infarction, and valve dysfunction. In vitro primary cardiomyocyte culture models have yielded numerous insights into the intrinsic and extrinsic mechanisms driving hypertrophic growth. However, due to limitations in current approaches, the dynamics of cardiomyocyte hypertrophic responses remain poorly characterized. In this study, we evaluate the application of the Holomonitor M4 digital holographic imaging microscope to track dynamic changes in cardiomyocyte surface area and volume in response to norepinephrine treatment, a model hypertrophic stimulus. The Holomonitor M4 permits non-invasive, label-free imaging of three-dimensional changes in cell morphology with minimal phototoxicity, thus enabling long-term imaging studies. Untreated and norepinephrine-stimulated primary neonatal rat cardiomyocytes were live-imaged on the Holomonitor M4, which was followed by image segmentation and single-cell tracking using the HOLOMONITOR App Suite software version 4.0.1.546. The 24 h treatment of cultured cardiomyocytes with norepinephrine increased cardiomyocyte spreading and optical volume as expected, validating the reliability of the approach. Single-cell tracking of both cardiomyocyte surface area and three-dimensional optical volume revealed dynamic increases in these parameters throughout the 24 h imaging period, demonstrating the potential of this technology to explore cardiomyocyte hypertrophic responses with greater temporal resolution; however, technological limitations were also observed and should be considered in the experimental design and interpretation of results. Overall, leveraging the unique advantages of the Holomonitor M4 digital holographic imaging system has the potential to empower future work towards understanding the molecular and cellular mechanisms underlying cardiomyocyte hypertrophy with enhanced temporal clarity.

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collected regarding cancer and drug-targeting approaches from well reputed databases including MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov, Science Direct, PubMed, Scopus, Wiley, and Springer. The articles published between January 2010 and December 2020 were considered. Due to the existence of various mechanisms, it is challenging to choose which one is appropriate for a specific case. Moreover, a combination of more than one approach is often utilized to achieve optimal drug effects. In this review, we have summarized and highlighted central mechanisms of how the targeted drug delivery system works in the specific diseased microenvironment, along with the strategies to make an approach more effective. We have also included some pictorial illustrations to have a precise idea about different types of drug targeting. The core contribution of this work includes providing a cancer drug development scientist with a broad preliminary idea to choose the appropriate approach among the various targeted drug delivery mechanisms. Also, the study will contribute to improving anticancer treatment approaches by providing a pathway for lesser side effects observed in conventional chemotherapeutic techniques.

Dendrimers: A New Race of Pharmaceutical Nanocarriers.

Dendrimers are nanosized, symmetrical molecules in which a small atom or group of atoms is surrounded by the symmetric branches known as dendrons. The structure of dendrimers possesses the greatest impact on their physical and chemical properties. They grow outwards from the core-shell which further reacts with monomers having one reactive or two dormant molecules. Dendrimers' unique characteristics such as hyperbranching, well-defined spherical structure, and high compatibility with the biological systems are responsible for their wide range of applications including medical and biomedical areas. Particularly, the dendrimers' three-dimensional structure can incorporate a wide variety of drugs to form biologically active drug conjugates. In this review, we focus on the synthesis, mechanism of drug encapsulations in dendrimers, and their wide applications in drug delivery.

Ethnopharmacological Inspections of Organic Extract of Oroxylum indicum in Rat Models: A Promising Natural Gift.

The stem bark of Oroxylum indicum (O. indicum) was aimed at testing for anti-inflammatory, antiulcerative, antihyperglycemic, and antidyslipidemic activities. Liver enzyme concentration (SGPT, SGOT) had also been assessed. After being extracted in organic solvent, 3 distinct doses, 100, 200, and 400 mg/kg b.w. (p.o.), were used. For edema formation 0.1 ml carrageenan at a dose of 1% w/v was injected into paw of left hind. It showed a fall of edemas 37.50%, 48.34%, and 55.83% while used doses were 100, 200, and 400 mg/kg b.w. (p.o.) individually. The EtOH extract of O. indicum (50%) and its fractions PET, CLF, EtOAc, and nBUT were studied against ethanol-induced gastric mucosal damage. Only PET and n-BuOH exhibited the highest percentage of protection and were 96% and 99%, respectively, persuaded by ethanol. In OGTT glibenclamide revealed reduction of glucose level to 7.55 ± 0.22 mmol/L from 10.57 ± 0.32 mmol/L after 30 minutes. Antihyperglycemic activities were assessed for 8- and 12-week duration in diabetic rats. Glibenclamide reduced glucose level from 33.50±0.31 to 7.90±0.19 mmol/L in 12 weeks. In 12 and 8 weeks, combination therapy lowered blood glucose level to a normal extent by 79% and 61% individually. In antidyslipidemic activities after 12-week treatment, it revealed simvastatin; MEOI (400 mg/kg b.w.) and combination of both reduced TC level by 44%, 28%, and 48% consequently followed by TG and LDL. In 8-week treatment, HDL levels were increased by 34%, 13%, and 36%, and in 12 weeks increased by 36%, 8%, and 38% consequently. Liver enzyme concentration after 12 weeks of treatment with glibenclamide, 400 mg/kg b.w. (p.o.) of MEOI and combination of both, exhibited the fact that concentration of SGPT showed downturn by 43.23%, 8.01%, and 54.86% and SGOT by 42.40%, 5.31%, and 44.85%. This study remarked that O. indicum has anti-inflammatory, antiulcer, antidiabetic, and antidyslipidemic potentials but has no ameliorative effect on liver enzyme.