Genomic insights into heart health: Exploring the genetic basis of cardiovascular disease.

Cardiovascular diseases (CVDs) are considered as the leading cause of death worldwide. CVD continues to be a major cause of death and morbidity despite significant improvements in its detection and treatment. Therefore, it is strategically important to be able to precisely characterize an individual's sensitivity to certain illnesses. The discovery of genes linked to cardiovascular illnesses has benefited from linkage analysis and genome-wide association research. The last 20 years have seen significant advancements in the field of molecular genetics, particularly with the development of new tools like genome-wide association studies. In this article we explore the profound impact of genetic variations on disease development, prognosis, and therapeutic responses. And the significance of genetics in cardiovascular risk assessment and the ever-evolving realm of genetic testing, offering insights into the potential for personalized medicine in this domain. Embracing the future of cardiovascular care, the article explores the implications of pharmacogenomics for tailored treatments, the promise of emerging technologies in cardiovascular genetics and therapies, including the transformative influence of nanotechnology. Furthermore, it delves into the exciting frontiers of gene editing, such as CRISPR/Cas9, as a novel approach to combat cardiovascular diseases. And also explore the potential of stem cell therapy and regenerative medicine, providing a holistic view of the dynamic landscape of cardiovascular genomics and its transformative potential for the field of cardiovascular medicine.

Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation.

OBJECTIVES: Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated. RESULTS: RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs. CONCLUSIONS: All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

Suppression of MAPK/NF-kB and activation of Nrf2 signaling by Ajugarin-I in EAE model of multiple sclerosis.

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H2 O2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.

Potential applications of PEGylated green gold nanoparticles in cyclophosphamide-induced cystitis.

We investigated the effect of green tea extract PEGylated gold nanoparticles (P-AuNPs) making use of its targeted and sustained drug delivery against cyclophosphamide (CYP)-induced cystitis. AuNPs were synthesized by reduction reaction of gold salts with green tea extract following the concept of green synthesis. Mostly spherical-shaped P-AuNPs were synthesized with an average size of 14.3 ± 3.3 nm. Pre-treatment with P-AuNPs (1, 10 mg/kg, i.p.) before CYP (150 mg/kg, i.p.) challenge suggested its uroprotective properties. P-AuNPs significantly reversed all pain-like behaviours and toxicities produced by CYP resulting in a decreased aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and creatinine level. P-AuNPs increased anti-oxidant system by increasing the level of reduced glutathione, glutathione-S-transferase, catalase and superoxide dismutase, and reduced nitric oxide production in bladder tissue. Additionally, it attenuated hypokalaemia and hyponatremia, along with a decrease in Evans blue content in bladder tissue and peritoneal cavity. CYP-induced bladder tissue damage observed by macroscopic and histological findings were remarkably attenuated by P-AuNPs, along with reduced fibrosis of collagen fibre in bladder smooth muscles shown by Masson's trichrome staining. Additionally, alterations in hematological parameters and clinical scoring were also prevented by P-AuNPs suggesting its uroprotective effect.