Revitalizing Ancient Mitochondria with Nano-Strategies: Mitochondria-Remedying Nanodrugs Concentrate on Disease Control.

Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad of vital functions across diverse cellular processes. Dysfunctions within mitochondria serve as catalysts for various diseases, prompting widespread cellular demise. Mounting research on remedying damaged mitochondria indicates that mitochondria constitute a valuable target for therapeutic intervention against diseases. But the less clinical practice and lower recovery rate imply the limitation of traditional drugs, which need a further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution and high efficacy by capitalizing on excellent nanomaterials and targeting drug delivery. Mitochondria-remedying nanodrugs have achieved ideal therapeutic effects. This review elucidates the significance of mitochondria in various cells and organs, while also compiling mortality data for related diseases. Correspondingly, nanodrug-mediate therapeutic strategies and applicable mitochondria-remedying nanodrugs in disease are detailed, with a full understanding of the roles of mitochondria dysfunction and the advantages of nanodrugs. In addition, the future challenges and directions are widely discussed. In conclusion, this review provides comprehensive insights into the design and development of mitochondria-remedying nanodrugs, aiming to help scientists who desire to extend their research fields and engage in this interdisciplinary subject.

The association between peritraumatic distress, perceived stress, depression in pregnancy, and NR3C1 DNA methylation among Chinese pregnant women who experienced COVID-19 lockdown.

Prenatal stress can affect pregnant women in an epigenetic way during the critical period of conception of their offspring. The study aims to investigate the relationship between peritraumatic distress, prenatal perceived stress, depression, and glucocorticoid receptor (NR3C1) DNA methylation among pregnant women who experienced COVID-19 lockdown in China. Study data were collected from 30 pregnant women in Wuhan and Huanggang, China. The Peritraumatic Distress Inventory was used to measure peritraumatic distress, the Edinburgh Postnatal Depression Scale was used to measure depressive symptoms, and the Perceived Stress Scale was used to measure perceived stress. DNA methylation in the exon 1F promoter region of NR3C1 gene from the venous blood mononuclear cell genome was characterized by bisulfite sequencing. Correlation and linear regression were used for data analysis. The mean level of peritraumatic distress, perceived stress, and depression was 6.30 (SD = 5.09), 6.50 (SD = 5.41), and 6.60 (SD = 4.85), respectively, with 23.33% of pregnant women being depressed. The mean NR3C1 methylation was 0.65 (SD = 0.22). Prenatal depression was positively correlated with the degree of methylation in venous blood from the mother (r = 0.59, p = 0.001), and depression predicted methylation of NR3C1 gene at the CpG 8 site (ß = 0.05, p = 0.03). No association was found between peritraumatic distress as well as perceived stress and methylation of NR3C1. NR3C1 gene was susceptible to epigenetic modification of DNA methylation in the context of prenatal stress, and maternal depression was associated with increased NR3C1 methylation among women who experienced COVID-19 lockdown.

Clinical Study on the Differential Diagnosis of High Myopia Astigmatism and Subclinical Keratoconus in Adolescents by Pentacam Anterior Segment Analyzer.

To explore the clinical value of Pentacam anterior segment analyzer in differential diagnosis of high myopia astigmatism and subclinical keratoconus in adolescents. The study included 100 teenagers with ophthalmic diseases treated at our hospital between July 2015 and August 2021, including 58 individuals with simple high myopia astigmatism (73 eyes in the simple high myopia astigmatism group) and 42 teenagers with subclinical keratoconus (51 eyes in the subclinical keratoconus group). The corneal parameters of the two groups were measured with a Pentacam anterior segment analyzer, and we compared the thinnest corneal thickness, anterior (posterior) vertex height of the thinnest point of the cornea, index of vertical asymmetry (IVA), index of height descent (IHD), and the average corneal pachymetric progression index. The receiver operating characteristic curve (ROC) was drawn to evaluate the value of various parameters and combined diagnostic factor Y in the differential diagnosis of high myopia astigmatism and subclinical keratoconus. The thinnest region of the cornea in the subclinical keratoconus group was less than that in the simple high myopia astigmatism group, while the anterior (posterior) vertex height of the thinnest point of the cornea, index of vertical asymmetry (IVA), index of height decentration (IHD), and average corneal pachymetric progression index were higher than those in the simple high myopia astigmatism group (P < 0.05). For the differential diagnosis of high myopia astigmatism and subclinical keratoconus, the combined diagnostic factor Y, anterior (posterior) vertex height, IVA, IHD, and mean corneal progression index were 0.808, 0.833, 0.868, 0.847, 0.684, and 0.926 (P < 0.05). The AUC of the combined diagnostic factory was the largest, which was significantly different from that of the anterior vertex height of the thinnest point of the cornea (Z = 3.280), the posterior vertex height of the thinnest point of the cornea (Z = 3.205), IVA (Z = 2.764), IHD (Z = 2.237), and the average corneal progression index (Z = 4.125) (P < 0.05). Using the Pentacam anterior segment analyzer, differential diagnoses can be made for high myopia, astigmatism, and subclinical keratoconus.

Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors.

Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.