A Randomized Trial of Oral Tranexamic Acid With Fluocinolone-Based Triple Cream Versus Fluocinolone Based Triple Cream Alone for the Treatment of Melasma.

Oral tranexamic acid (TXA) is a relatively new treatment option for melasma. It is thought to reduce hyperpigmentation through inhibition of the plasminogen/plasmin pathway with resulting decreases in epidermal melanocyte tyrosinase activity, inflammatory mediators, dermal neovascularization, and mast cell numbers.

Anti-diabetic and anti-lipidepmic effect of Albizia lebbeck seeds against HepG2 cells.

Albizia lebbeck has been a medicinally important plant for its pharmacological potential. This study aims to determine the in vitro antioxidant, anti-diabetic and anti-lipidemic potential of A. lebbeck seeds. The seed extracts were prepared in petroleum ether, chloroform and methanol. Crude methanolic extract (ME ext) was subjected further to sequential fractionation in increasing polarity based solvents. Extracts and fractions were analyzed for their antioxidant, anti-diabetic and anti-lipidemic potentials using hepatic cell line, HepG2. Results showed that crude extracts of A. lebbeck seeds specifically, ME ext are rich in polyphenols and flavonoids. ME ext has also shown highly significant antioxidant and alpha-amylase inhibition potential compared to petroleum ether and chloroform extracts. In vitro assays using different fractions of methanolic extract further highlighted the ethyl acetate and chloroform fractions exhibiting significant antioxidant and anti-diabetic potentials. Alpha-amylase inhibition coupled with enhanced glucose uptake of cells treated with ME ext and ethyl acetate fraction emphasized on significant anti-diabetic potential of the plant. Expression alteration of genes and reduced level of cholesterol suggested the lipid synthesis mediated anti-diabetic activity of the plant. It is therefore, concluded that A. lebbeck seed has significant antioxidant, anti-diabetic and anti-lipidemic potentials.

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions.

Myocardial infarction (MI) is one of the leading causes of heart-related deaths worldwide. Following MI, the hypoxic microenvironment triggers apoptosis, disrupts the extracellular matrix and forms a non-functional scar that leads towards adverse left ventricular (LV) remodelling. If left untreated this eventually leads to heart failure. Besides extensive advancement in medical therapy, complete functional recovery is never accomplished, as the heart possesses limited regenerative ability. In recent decades, the focus has shifted towards tissue engineering and regenerative strategies that provide an attractive option to improve cardiac regeneration, limit adverse LV remodelling and restore function in an infarcted heart. Acellular scaffolds possess attractive features that have made them a promising therapeutic candidate. Their application in infarcted areas has been shown to improve LV remodelling and enhance functional recovery in post-MI hearts. This review will summarise the updates on acellular scaffolds developed and tested in pre-clinical and clinical scenarios in the past five years with a focus on their ability to overcome damage caused by MI. It will also describe how acellular scaffolds alone or in combination with biomolecules have been employed for MI treatment. A better understanding of acellular scaffolds potentialities may guide the development of customised and optimised therapeutic strategies for MI treatment.

In vitro antioxidant potential and antiproliferative activity of Aesculus indica seed extract against hepatocellular carcinoma cell line.

Therapeutic secondary metabolites have gained immense attention in recent years due to their effective medicinal properties. Aesculus indica is a medicinally important plant being traditionally used for various ailments. The present study aimed to determine the antioxidant and antiproliferative activities of seeds of A. indica. The crude methanolic seed extract was prepared and subjected to sequential fractionation in increasing polarity. The extract and its fractions were investigated for antioxidant activities using various in vitro assays. Further, the extract along with its potential antioxidant fractions were analyzed for their cytotoxic activity against HepG2, human hepatocyte carcinoma cells through bioassays. The results showed highly significant antioxidant potential of methanolic extract of A. indica seeds and two of its fractions prepared with chloroform and ethyl acetate. The studies on hepatocyte carcinoma cells further revealed that the extract and two of its potential antioxidant fractions significantly induced cytotoxicity and inhibited migration, proliferation, clonogenicity and 3D growth of HepG2 cells. It is therefore, concluded that A. indica possess significant antioxidant and cytotoxic potential against HepG2 cells and with further research can be proposed for therapeutic interventions.

Numerical Approximation of a Nonequilibrium Model of Gradient Elution Chromatography Considering Different Functional Relationships between Model Parameters and Solvent Composition.

In this paper, a rigorous theoretical study is conducted to analyze the influence of varying solvent compositions on the retention characteristics of elution profiles within a fixed-bed liquid chromatographic column. In gradient chromatography, the propagation speed of elution profiles is manipulated through a progressive variation in the mobile-phase composition. Consequently, enhanced separation of the mixture components can be achieved together with a reduction in the requisite recycling times for subsequent injections. In other words, both the efficiency and the selectivity of the column can be enhanced. The lumped kinetic model coupled with the convection-diffusion equation for the volume fraction of the solvent is applied to simulate the process. The resulting nonlinear model equations are numerically solved by applying a semidiscrete second-order finite-volume method. The numerical solutions are utilized to quantify the effects of gradient starting and ending times, solvent composition, solvent strength parameters, and gradient slope on the concentration profiles. Additionally, temporal numerical moments are plotted versus the starting and ending times of the gradient, and standard performance criteria are presented for evaluating the process performance. The outcomes of this investigation will contribute to further enhancements in gradient elution chromatography.

Theoretical Investigation of the Nonlinear General Rate Model with the Bi-Langmuir Adsorption Isotherm Using Core-Shell Adsorbents.

Core-shell particles enable the separation of intricate mixtures in a highly efficient and rapid manner. The porous shell particles increased the separation efficiency with expedited flow rates due to an abatement in the pore volume accessible for longitudinal diffusion and a decrease in diffusion path length. This study focuses on the numerical approximation of a nonlinear isothermal general rate model applied to stationary bed columns that are replete with inert core adsorbents featuring double adsorption sites. The transport of solute in heterogeneous porous media can be modeled by a nonlinear convection acquiescent partial differential equation system together with a specific nonlinear algebraic relation: the bi-Langmuir adsorption isotherm. Therefore, it is important to develop accurate and reliable numerical techniques that can perform accurate numerical simulations of these models. We extended and implemented a second-order, semidiscrete, high-resolution finite volume method to simulate the governing equations of the model. Single solute flow and multi component mixture flows are assessed through a series of numerical experiments to theoretically illustrate the repercussions of intraparticle diffusion, film mass resistance, axial dispersion, and the size of the inert core radius upon simulated elution curves. Standard performance criteria are assessed to determine the optimal core radius fraction range for optimizing the separation performance.

Theoretical Analysis of a Nonequilibrium Transport Model of Two-Dimensional Nonisothermal Reactive Chromatography Accounting for Bi-Langmuir Isotherm.

The current study investigates a nonequilibrium and nonlinear two-dimensional lumped kinetic transport model of nonisothermal reactive liquid chromatography, considering the Bi-Langmuir adsorption isotherm, heterogeneous reaction rates, radial and axial concentration variations, and the adsorption and reaction enthalpies. The mathematical models of packed bed chromatographic processes are expressed by a highly nonlinear system of coupled partial differential algebraic equations connecting the phenomena of convection, diffusion, and reaction, for mass and energy balance, the differential algebraic equations for mass balance in the solid phase, and the algebraical expressions for the adsorption isotherms and for the reaction rates. The nonlinearity of the reaction term and the adsorption isotherm preclude the derivation of an analytical solution for the model equations. For this reason, a semidiscrete, high-resolution, finite-volume technique is extended and employed in this study to obtain the numerical solution. Several consistency checks are performed to evaluate the model predictions and analyze the precision of the proposed numerical scheme. A number of heterogeneously catalyzed stoichiometric reactions are numerically simulated to examine reactor performance under the influence of temperature and Bi-Langmuir adsorption dynamics, the level of coupling between mass and energy fronts, and to study the effects of various critical parameters. The numerical results obtained are beneficial for optimal predictive control and process optimization during production and the development of methods for systematic design and fault detection of nonisothermal liquid chromatographic reactors, and hence constitute the first step to provide deeper insight into the overall evaluation of integrated reaction and separation processes.

Direct Reprogramming of Resident Non-Myocyte Cells and Its Potential for In Vivo Cardiac Regeneration.

Cardiac diseases are the foremost cause of morbidity and mortality worldwide. The heart has limited regenerative potential; therefore, lost cardiac tissue cannot be replenished after cardiac injury. Conventional therapies are unable to restore functional cardiac tissue. In recent decades, much attention has been paid to regenerative medicine to overcome this issue. Direct reprogramming is a promising therapeutic approach in regenerative cardiac medicine that has the potential to provide in situ cardiac regeneration. It consists of direct cell fate conversion of one cell type into another, avoiding transition through an intermediary pluripotent state. In injured cardiac tissue, this strategy directs transdifferentiation of resident non-myocyte cells (NMCs) into mature functional cardiac cells that help to restore the native tissue. Over the years, developments in reprogramming methods have suggested that regulation of several intrinsic factors in NMCs can help to achieve in situ direct cardiac reprogramming. Among NMCs, endogenous cardiac fibroblasts have been studied for their potential to be directly reprogrammed into both induced cardiomyocytes and induced cardiac progenitor cells, while pericytes can transdifferentiate towards endothelial cells and smooth muscle cells. This strategy has been indicated to improve heart function and reduce fibrosis after cardiac injury in preclinical models. This review summarizes the recent updates and progress in direct cardiac reprogramming of resident NMCs for in situ cardiac regeneration.

Role of Chaperone-Mediated Autophagy in Ageing Biology and Rejuvenation of Stem Cells.

What lies at the basis of the mechanisms that regulate the maintenance and self-renewal of pluripotent stem cells is still an open question. The control of stemness derives from a fine regulation between transcriptional and metabolic factors. In the last years, an emerging topic has concerned the involvement of Chaperone-Mediated Autophagy (CMA) as a key mechanism in stem cell pluripotency control acting as a bridge between epigenetic, transcriptional and differentiation regulation. This review aims to clarify this new and not yet well-explored horizon discussing the recent studies regarding the CMA impact on embryonic, mesenchymal, and haematopoietic stem cells. The review will discuss how CMA influences embryonic stem cell activity promoting self-renewal or differentiation, its involvement in maintaining haematopoietic stem cell function by increasing their functionality during the normal ageing process and its effects on mesenchymal stem cells, in which modulation of CMA regulates immunosuppressive and differentiation properties. Finally, the importance of these new discoveries and their relevance for regenerative medicine applications, from transplantation to cell rejuvenation, will be addressed.

Silica Nanoparticle Internalization Improves Chemotactic Behaviour of Human Mesenchymal Stem Cells Acting on the SDF1α/CXCR4 Axis.

Human mesenchymal stem cell (hMSC)-based therapy is an emerging resource in regenerative medicine. Despite the innate ability of hMSCs to migrate to sites of injury, homing of infused hMSCs to the target tissue is inefficient. It was shown that silica nanoparticles (SiO2-NPs), previously developed to track the stem cells after transplantation, accumulated in lysosomes leading to a transient blockage of the autophagic flux. Since CXCR4 turnover is mainly regulated by autophagy, we tested the effect of SiO2-NPs on chemotactic migration of hMSCs along the SDF1α/CXCR4 axis that plays a pivotal role in directing MSC homing to sites of injury. Our results showed that SiO2-NP internalization augmented CXCR4 surface levels. We demonstrated that SiO2-NP-dependent CXCR4 increase was transient, and it reversed at the same time as lysosomal compartment normalization. Furthermore, the autophagy inhibitor Bafilomycin-A1 reproduced CXCR4 overexpression in control hMSCs confirming the direct effect of the autophagic degradation blockage on CXCR4 expression. Chemotaxis assays showed that SiO2-NPs increased hMSC migration toward SDF1α. In contrast, migration improvement was not observed in TNFα/TNFR axis, due to the proteasome-dependent TNFR regulation. Overall, our findings demonstrated that SiO2-NP internalization increases the chemotactic behaviour of hMSCs acting on the SDF1α/CXCR4 axis, unmasking a high potential to improve hMSC migration to sites of injury and therapeutic efficacy upon cell injection in vivo.

Citrullus colocynthis-Mediated Green Synthesis of Silver Nanoparticles and Their Antiproliferative Action against Breast Cancer Cells and Bactericidal Roles against Human Pathogens.

The present study investigated the biomedical potential of eco-friendly Citrullus colocynthis-mediated silver nanoparticles (Cc-AgNPs). The antibacterial efficacy of Cc-AgNPs was evaluated against two multidrug-resistant pathogenic bacterial strains, Escherichia coli and Pseudomonas aeruginosa. The antiproliferative and antilipidemic performance of the prepared particles was determined against the MCF7 cell line, a breast cancer cell line. The in vitro antibacterial assay revealed that Cc-AgNPs induced dose-dependent bactericidal activity, as a considerable increase in the zone of inhibition (ZOI) was noted at higher concentrations. Reduced proliferation, migration, spheroid size, and colony formation exhibited the substantial antiproliferative potential of Cc-AgNPs against MCF7 cells. Significant alterations in the expression of cell surface markers, apoptosis, and cell proliferation genes further confirmed the antiproliferative impact of Cc-AgNPs. Moreover, Cc-AgNPs exhibited antilipidemic activity by reducing cellular cholesterol and triglyceride levels and regulating key genes involved in lipogenesis. In conclusion, these results propose that Cc-AgNPs can be employed as a potent tool for future antibacterial and anticancer applications.

Methanolic extract of Citrullus colocynthis suppresses growth and proliferation of breast cancer cells through regulation of cell cycle.

Breast cancer is a major cause of cancer related deaths in women worldwide. Available treatments pose serious limitations such as systemic toxicity, metastasis, tumor recurrence, off-target effects, and drug resistance. In recent years, phytochemicals such as secondary metabolites due to their effective anticancer potential at very low concentration have gained attention. Aim of the study was to evaluate anticancer potential of Citrullus colocynthis and its possible molecular targets on MCF-7, a human breast cancer cell line. Methanolic extract of leaves was prepared and fractionated by solvents (n-hexane, chloroform, ethyl acetate and n-butanol) with increasing polarity. Bioassays and gene expression regulation was conducted to evaluate the anticancer activity, proliferation rate and cell cycle regulation of breast cancer cells treated with extract and its fractions, separately. Results showed a significant anticancer activity of methanolic extract of C. colocynthis and two of its fractions prepared with chloroform and ethyl acetate. Bioassays depicted significant decrease in proliferation and growth potential along with cell cycle arrest of treated cells compared to control untreated cells. Expression regulation of genes further confirmed the cell cycle arrest through significant upregulation of cyclin-CDK inhibitors (p21 and p27) and cell cycle checkpoint regulators (HUS1, RAD1, ATM) followed by downregulation of downstream cell cycle progression genes (Cyclin A, Cyclin E, CDK2). It is concluded that C. colocynthis arrests cell cycle in human breast cancer cells through expression regulation of cyclin-CDK inhibitors and with further research can be proposed for therapeutic interventions.

Citrullus colocynthis regulates de novo lipid biosynthesis in human breast cancer cells.

BACKGROUND: Reprogrammed energy metabolism is considered a hallmark of cancer and is proposed as an important target for therapy. Uncontrolled and infinite cell proliferation needs efficient energy sources. To meet the demands of cancer cells lipid metabolism is activated. Citrullus colocynthis is a traditional medicinal plant known for its anticancer and hypolipidemic effects. AIMS: Aim of the current study was to assess the effect of C. colocynthis leaves on regulation of lipid metabolism in MCF-7, a human breast cancer cell line. METHODS: Methanolic extract of leaves and its fractions in increasing polarity-based solvents (n-hexane, chloroform, ethyl acetate and n-butanol) were prepared and analyzed for the presence of secondary metabolites in each fraction. Bioassays and apoptosis genes expression analysis was conducted to evaluate the anticancer and cytotoxic effect of breast cancer cells treated with extract and its fractions, separately. Lipid quantification and gene expression regulation of genes involve in lipid metabolism was performed to evaluate regulation of lipid metabolism. RESULTS: Results showed a significant anticancer activity of methanolic extract of C. colocynthis and two of its fractions prepared with chloroform and ethyl acetate. Quantification of lipids depicted significant increase in cholesterol and increase in triglycerides of treated cells compared to control untreated cells. Expression regulation of genes further confirmed the lipid regulation through significant down regulation of genes involve in lipid metabolism (FASN, HMGCLL1, ACSL5 and ELOVL2). CONCLUSION: The present study concludes that C. colocynthis holds strong anticancer potential through regulation of lipid metabolism and with further studies can be proposed for novel therapeutic approaches.