From genes to therapy: A comprehensive exploration of congenital heart disease through the lens of genetics and emerging technologies.

Congenital heart disease (CHD) affects approximately 1 % of live births worldwide, making it the most common congenital anomaly in newborns. Recent advancements in genetics and genomics have significantly deepened our understanding of the genetics of CHDs. While the majority of CHD etiology remains unclear, evidence consistently indicates that genetics play a significant role in its development. CHD etiology holds promise for enhancing diagnosis and developing novel therapies to improve patient outcomes. In this review, we explore the contributions of both monogenic and polygenic factors of CHDs and highlight the transformative impact of emerging technologies on these fields. We also summarized the state-of-the-art techniques, including targeted next-generation sequencing (NGS), whole genome and whole exome sequencing (WGS, WES), single-cell RNA sequencing (scRNA-seq), human induced pluripotent stem cells (hiPSCs) and others, that have revolutionized our understanding of cardiovascular disease genetics both from diagnosis perspective and from disease mechanism perspective in children and young adults. These molecular diagnostic techniques have identified new genes and chromosomal regions involved in syndromic and non-syndromic CHD, enabling a more defined explanation of the underlying pathogenetic mechanisms. As our knowledge and technologies continue to evolve, they promise to enhance clinical outcomes and reduce the CHD burden worldwide.

Development of chitosan-hyaluronic acid based hydrogel for local delivery of doxycycline hyclate in an ex vivo skin infection model.

Doxycycline hyclate (DOXY) is a tetracycline derivative known as the broad-spectrum bacteriostatic drug. DOXY has been suggested as the first-line antibiotic for diabetic foot ulcers (DFU). Unfortunately, the long-term availability of DOXY in both oral and conventional topical dosage forms reduces its therapeutic effectiveness, which is closely linked to gastrointestinal side effects and acute pain during therapy, as well as uncontrolled DOXY release at the wound site. To address these shortcomings, we present for the first time a DOXY hydrogel system (DHs) built on crosslinks between carboxymethyl chitosan (CMC) and aldehyde hyaluronic acid (AHA). Three formulations of DHs were developed with different ratios of CMC and AHA, consisting of F1 (3:7, w/w), F2 (5:5, w/w), and F3 (7:3, w/w). Viscosity, rheology, gel strength, pH, swelling, gel fraction, wettability, stability, in vitro drug release, ex vivo antibacterial, and dermatokinetic studies were used to evaluate the DHs. According to the in vitro release study, up to 85% of DOXY was released from DHs via the Fickian diffusion mechanism in the Korsmeyer-Peppas model (n < 0.45), which provides controlled drug delivery. Because of its excellent physicochemical characteristics, F2 was chosen as the best DHs formulation in this study. Essentially, the optimum DHs formulation could greatly improve DOXY's ex vivo dermatokinetic profile while also providing excellent antibacterial activity. As a consequence, this study had promising outcome as a proof of concept for increasing the efficacy of DOXY in clinical therapy. Further extensive in vivo studies are required to evaluate the efficacy of this approach.

Enhanced skin localization of metronidazole using solid lipid microparticles incorporated into polymeric hydrogels for potential improved of rosacea treatment: An ex vivo proof of concept investigation.

Metronidazole (MNZ) is a nitroimidazole derivative antibiotic that has been generally used in the treatment of rosacea. However, it has low molecular weight and lipophilicity, limiting the effectiveness of MNZ in the topical treatment of rosacea. This study reports an MNZ-loaded solid lipid microparticle (SLM) gel formulation with sustained drug release effects required in the treatment of rosacea. SLM was formulated using the double emulsification method with five different concentrations of glyceryl monostearate (GMS) as a solid lipid used to encapsulate MNZ. All the MNZ-loaded SLM formulas were extensively characterized by various analytical tools. After optimized MNZ-loaded SLM formulation was obtained, then formulated into gel preparation. To obtain a gel formula with good physical characteristics and drug release in the development of topical therapy, the SLM-loaded gel was further evaluated, covering various parameters such as pH, viscosity, rheology, spreadability, extrudability, skin occlusivity, gel strength, permeation and retention ex vivo, as well as hemolysis tests and antioxidant activity. The evaluation results showed that the SLM formulations had desired properties with optimum encapsulation efficiency. Moreover, the gels prepared from carbomer possessed desired characteristics and were found to be hemocompatible. In addition, the gel formula with a carbomer concentration of 1.25 % can provide better drug release with the highest MNZ retention after 24 h of 2.35 ± 0.05 mg. Notably, the formulation of MNZ into SLM and hydrogel did not affect the antioxidant activity. Thus, it can provide continuous drug release, which could potentially be useful in increasing efficacy in rosacea therapy. The results obtained also showed a significant difference (p < 0.05) compared to the control formula and other formulas. Therefore, this study has proven a new approach to developing drug delivery systems for rosacea treatment.

Effect of orally administered combination of Caulerpa racemosa and Eleutherine americana (Aubl) Merr extracts on phagocytic activity of macrophage.

BACKGROUND AND PURPOSE: Polysaccharide sulfate is a major active phytochemical constituent of Caulerpa racemosa, whereas the Eleutherine americana (Aubl) Merr has antioxidant properties. The aim of this research was to investigate the combined effect of polysaccharide sulfate that was isolated from C. racemosa and E. americana on the macrophage activity. EXPERIMENTAL APPROACH: The phenolic contents and antioxidant activities of E. americana extracts in water and various ethanol concentrations were studied using the Folin-Ciocalteu and 2,2-diphenyl-1-picryl-hydrazyl- hydrate (DPPH) methods, respectively. Polysaccharide sulfate was isolated from C. racemosa by precipitation method. To assess the macrophage activity, mice were treated orally for 14 days with either a combination of polysaccharide sulfate and E. americana 96% ethanol extract at a specific ratio or with each extract alone. Macrophages were isolated and the phagocytic activity was measured by assessing the ability of the macrophages to phagocytose latex particles and nitric oxide (NO) levels were assessed using a colorimetric assay. FINDINGS / RESULTS: The E. americana crude extract in water exhibited the highest yield (13.04%), compared with the extract in 96% ethanol, which had the highest phenolic content (6.37 ± 0.16 mg/g gallic acid equivalent) and the strongest antioxidant activity (IC50, 22.63 ± 1.09 µg/mL). The combination of extracts, when both extracts were administered at 65:65 mg/kg BW, resulted in the highest increases in phagocytosis activity (62.73 ± 5.77%) and NO levels (16.43 ± 1.37 µmol/L). CONCLUSION AND IMPLICATIONS: The results of this study confirmed the non-specific immunostimulant properties of the combination of polysaccharide sulfate and E. americana and justified their use in traditional medicine. The observed increase in macrophage activity appeared to be correlated with the increased ability of mice to fight infection.