Current Pharmaceutical Design - Volume 31, Issue 41, 2025

Cardiovascular disorders (CVDs) are the primary cause of mortality globally, and the community is significantly affected when young people suffer from CVDs. Coronary artery disease, myocardial infarction, fibrosis, atherosclerosis, pulmonary arterial hypertension, thrombosis, and ischemic diseases are different types of CVDs, which encompass a wide range of conditions that interfere with the functioning of the cardiovascular system. The relevance of nanotechnology in the treatment of CVDs has emerged progressively in previous decades.

This review offers concise insights into the physiochemical characteristics of poly (lactic-co-glycolic acid) (PLGA) imperative for drug delivery. This article highlights the application of PLGA-NPs in myocardial ischemia, atherosclerosis, myocardial infarction, pulmonary artery hypertension, valvular heart disease, tumour thrombus, cardiac myocyte, restenosis, cardiovascular theranostics, vascular disorders, and angiogenesis. Further, this review gives updates about published patents pertaining to the current state-of-art about PLGA-NPs in CVDs.

An extensive review was undertaken employing the Google Scholar, PubMed, and ScienceDirect databases using scientific papers published in peer-reviewed journals from 2000 to 2024.

Owing to their minuscule size and increased surface area accessible for surface functionalization, the PLGA-NPs offer a cutting-edge technology to provide an efficient platform for controlled and targeted drug delivery, therefore, imparting tremendous relevance in reducing the occurrence of CVDs.

This has been concluded that PLGA is the highly effective biodegradable copolymer, also known as “Smart polymers,” because of their biodegradability, biocompatibility, controlled drug release profile, and potential for surface modification with targeting molecules.

Inflammation and nutritional status have significant roles in frailty. While albumin and the albumin-to-globulin ratio (AGR) are recognized as inflammatory and nutritional biomarkers, and globulin is associated with inflammation, their relationships with frailty remain underexplored. This study explored the relationships between albumin, globulin, AGR, and frailty among middle-aged and older adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database.

The study was a cross-sectional study with participants aged ≥45 years from the 2013-2014 NHANES database. The frailty assessment was based on a 36-item index of frailty constructed in NHANES, excluding nutritional indicators. The relationships between albumin, globulin, AGR, and frailty were analyzed using weighted multivariate regression analyses, smooth curve fitting, two-segment linear regression models, subgroup analyses, and interaction tests.

This study involved 1,506 middle-aged and older participants, with a frailty rate of 42.23%. Nonlinear relationships were identified between albumin, AGR, and frailty, while a linear relationship was observed between globulin and frailty. Two-segment linear regression models demonstrated that the inflection points for albumin and AGR were 3.90 and 1.91, respectively. On the left side of these inflection points, albumin and AGR were negatively associated with the prevalence of frailty. On the right side of these inflection points, albumin and AGR were not significantly associated with the prevalence of frailty.

This study reveals two threshold effects on frailty in middle-aged and older adults: albumin and AGR. Below specific thresholds, both are linked to reduced frailty risk, but above these levels, neither shows a significant association. Globulin, however, consistently correlates with increased frailty. These findings highlight nonlinear relationships between albumin, AGR, and frailty, suggesting that maintaining optimal levels of these biomarkers may help prevent frailty.

Hemostatic dental sponges are biodegradable materials and fast hemostats that can help blood clotting in the surgical site and quick repair of the dental surgery site. In this study, we investigated the bleeding control (blood absorption ability and active bleeding) of a hemostatic gelatin sponge containing aloe vera nanoparticles as a hemostatic material after the removal of mandibular posterior teeth in a double-blind, randomized trial.

A clinical trial was performed on 30 patients (13 males and 17 females) who were referred to the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, for extraction of two mandibular molars. The plan was a split-mouth, randomized, double-blind clinical trial. To investigate the blood absorption ability of a hemostatic sponge containing aloe vera nanoparticles in each patient after tooth extraction, the sponge was placed in the socket of the extracted tooth. Sterile gauze was placed on the hemostat sponge containing aloe vera nanoparticles (test group). For the control group, the same process was repeated with a sponge without aloe vera nanoparticles. The number of used sterile gauzes was recorded and the mean excess blood weight was measured with a digital scale. Also, the amount of bleeding after 1 and 4 hours of tooth extraction was recorded for all patients as an active bleeding time.

The number of sterile gauzes used and the mean excess blood weight used in each group indicate blood absorption. The results showed that there was no significant difference in the amount of sterile gauze between the two groups (P=0.65). In both groups, the consumption of three sterile gauzes was the most frequent. However, the mean excess blood weight in the control group was significantly higher, which indicates the better efficiency of the test group (P=0.04). Besides, the examination of the patients showed that in none of the patients of the two groups, active bleeding was observed 1 and 4 hours after tooth extraction.

The performance of the test sponge was better than the control sponge in controlling bleeding after tooth extraction. It seems that the obtained results cannot only be related to the presence of aloe vera nanoparticles. The differences in the bleeding control (blood absorption ability and the active bleeding time) for the used sponges can also influence the results. In addition, the use of aloe vera in the form of nanoparticles can contribute to early healing effects and other beneficial effects, such as antimicrobial effects in the tooth-extracted site.

Poly (ADP-ribose) polymerase 12 (PARP12) plays a crucial role in DNA damage response (DDR) through DNA repair, maintaining genomic stability. Mutations in PARP12 contribute to genomic instability, leading to cancer progression. Targeting PARP12 mutants with small molecule inhibitors offers a promising therapeutic strategy.

This study aims to identify potent inhibitors for PARP12 mutants using molecular docking-based virtual screening from the National Cancer Institute (NCI) compound library, followed by molecular dynamics (MD) simulations to validate binding stability.

Homology models of human PARP12 mutants were developed for virtual screening. The top-scoring compounds were refined through molecular docking, and their stability was analyzed using all-atomistic MD simulations. Binding free energy (MMGBSA) calculations and structural dynamics assessments, including RMSD, RMSF, RoG, and SASA, were conducted to evaluate the drug-receptor interactions.

Three promising inhibitors, NCI-32743, NCI-32982, and NCI-659779, demonstrated high binding affinity and stability with PARP12 mutants. These compounds showed significant inhibitory potential, maintaining strong interactions with the target protein throughout the simulation period. ADMET and pharmacokinetic analyses confirmed their drug likeness and potential for further development.

The identified inhibitors exhibit strong potential for targeting PARP12 mutants in cancer therapy. Further in vitro and in vivo studies are required to confirm their efficacy and therapeutic viability for clinical applications.

This study is formulated to reveal the variables affecting the radio-sensitivity in lung adenocarcinoma (LUAD).

LUAD patients show varied radiotherapy responses. While epidermal growth factor receptor (EGFR) mutations are often used to predict sensitivity, their reliability is debated, underscoring the need for better biomarkers.

The aim of this study was to identify key functional proteins that regulate the sensitivity of LUAD to radiotherapy and to assess the potential value of exosomal LAMC1 as a clinical predictive marker.

In this study, 103 LUAD patients receiving concurrent radiotherapy were included to assess the relationship between EGFR mutation and survival. Intrinsic radio-sensitivity and different radio-sensitivities in 14 LUAD cell lines with/out EGFR mutation were examined based on the surviving fraction at 2 Gy (SF2). Data-independent acquisition (DIA) and Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics were used to investigate the proteomics of the LUAD cell lines. Subsequently, GO/KEGG enrichment analysis was combined with protein-protein interaction (PPI) network screening for key proteins. Nano-flow cytometry was employed to validate changes in radiosensitivity-associated protein expression within exosomes, while siRNA-mediated knockdown was performed to assess the functional impact of specific proteins on LUAD cells.

EGFR mutations were not significantly associated with progression-free survival (PFS)/overall survival (OS). 14 LUAD cell lines displayed intrinsic variations in SF2, and no difference between the EGFR mutation and wild-type groups was reported. 5425 proteins were identified via DIA in 14 LUAD cell lines. After bio-informatics analysis, LAMC1, ITGB4, ITGA6, and CD44 were the most representative core differential proteins for the radio-sensitivity in LUAD cells. Notably, LAMC1 was confirmed as a radiation-resistant protein. Following radiotherapy, LUAD cells secreted exosomes with reduced LAMC1 levels. Moreover, LAMC1 knockdown significantly affected cellular proliferation and apoptosis following the irradiation.

LAMC1 serves as a critical functional determinant of radiotherapy resistance in LUAD. Its dynamic changes in exosomes demonstrate potential for predicting radiotherapy response, suggesting clinical utility for radiosensitivity assessment and personalized radiotherapy guidance.