Two interaction surfaces between XPA and RPA organize the preincision complex in nucleotide excision repair.

The xeroderma pigmentosum protein A (XPA) and replication protein A (RPA) proteins fulfill essential roles in the assembly of the preincision complex in the nucleotide excision repair (NER) pathway. We have previously characterized the two interaction sites, one between the XPA N-terminal (XPA-N) disordered domain and the RPA32 C-terminal domain (RPA32C), and the other with the XPA DNA binding domain (DBD) and the RPA70AB DBDs. Here, we show that XPA mutations that inhibit the physical interaction in either site reduce NER activity in biochemical and cellular systems. Combining mutations in the two sites leads to an additive inhibition of NER, implying that they fulfill distinct roles. Our data suggest a model in which the interaction between XPA-N and RPA32C is important for the initial association of XPA with NER complexes, while the interaction between XPA DBD and RPA70AB is needed for structural organization of the complex to license the dual incision reaction. Integrative structural models of complexes of XPA and RPA bound to single-stranded/double-stranded DNA (ss/dsDNA) junction substrates that mimic the NER bubble reveal key features of the architecture of XPA and RPA in the preincision complex. Most critical among these is that the shape of the NER bubble is far from colinear as depicted in current models, but rather the two strands of unwound DNA must assume a U-shape with the two ss/dsDNA junctions localized in close proximity. Our data suggest that the interaction between XPA and RPA70 is key for the organization of the NER preincision complex.

Identification and Molecular Docking Analysis of Angiotensin-Converting Enzyme Inhibitors from Finger Millet (Eleusine coracana).

Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.

Development of gelatinized-core liposomes for the oral delivery of EGCG with improved stability, release property, and cellular antioxidant activity.

Epigallocatechin gallate (EGCG) exhibits antioxidant, anti-cancer, and anti-inflammatory properties; however, low cellular permeability and stability limit its bioavailability. Liposomes have the potential for enhancing bioactive compounds' bioavailability. Yet, low entrapment efficiency (EE) and burst release of hydrophilic substances make them impractical for food industry use. Here, we incorporated gelatin into liposomes to overcome these limitations. EGCG-loaded conventional liposomes (EGCG/CLs) and gelatinized-core liposomes (EGCG/GLs) had small particle sizes and high absolute zeta potentials. Encapsulation in EGCG/GLs significantly improved the EE of EGCG compared to that in EGCG/CLs (p < 0.05). EGCG/GLs retained EGCG in the hydrophilic region, whereas EGCG/CLs exhibited significantly higher release of EGCG during storage (p < 0.05). Additionally, in comparison to EGCG/CLs, gelatin incorporation significantly enhanced the sustained release, cellular permeability, and cellular antioxidant activity of EGCG (p < 0.05). This study emphasizes the capability of gelatinized-core liposomes as a potent delivery system for enhancing the stability and bioavailability of EGCG/CLs, broadening the prospects for utilizing them in the food industry.

Comparison of the anti-diabetic effects of various grain and legume extracts in high-fat diet and streptozotocin-nicotinamide-induced diabetic rats.

The anti-diabetic properties of whole groats and dietary fibers from various grains and legumes are well known. Nevertheless, studies on the anti-diabetic effects of their extracts are limited, and it is difficult to compare their efficacy. This study investigated the anti-diabetic potential of ethanol extracts from oats (OE), sorghum (SE), foxtail millet (FE), proso millet (PE), adzuki bean (AE), and black soybean (BE) in a high-fat diet and streptozotocin-nicotinamide-induced diabetic rat models. The extracts, obtained using 99.9 % ethanol, were orally administered to diabetic rats for four weeks. Various parameters were evaluated, including fasting blood glucose levels, glucose tolerance, insulin sensitivity, serum insulin levels, and pancreas histological analysis. OE and SE effectively reduced fasting blood glucose levels and the area under the curve (AUC) in the oral glucose tolerance test. Only OE significantly decreased the AUC in the insulin tolerance test and increased insulin concentration and homeostatic model assessment of the ß-cell function index, indicating improved insulin sensitivity and ß-cell function. Histological and immunohistochemical analysis of the pancreas supported these findings, demonstrating that OE protected against pancreatic cell damage. In contrast, FE, PE, AE, and BE did not have a significant effect on diabetes-related parameters. These findings identify OE as the most promising natural intervention for diabetes management.

Antihypertensive effects of the combined extract of Sorghum bicolor, Vigna angularis, and Eleusine coracana in spontaneously hypertensive rats.

This study investigated the antihypertensive effects of the combined extract of sorghum, adzuki bean, and finger millet (SAFE) on spontaneously hypertensive rats. The rats were divided into four groups (n = 8): WKY, SHR, SAFE (500 mg/kg SAFE), and CAP (50 mg/kg captopril). SAFE significantly decreased the lean-to-fat mass ratio with no notable changes in body weight, food intake, or food efficiency ratio, and it effectively lowered both systolic and diastolic blood pressures, comparable to CAP. Moreover, it significantly reduced the cardiac mass index and alleviated cardiac fibrosis. SAFE did not induce hepatotoxicity, as indicated by the maintenance of aspartate aminotransferase and alanine aminotransferase levels in the normal range, confirming its safety. Taken together, these findings suggested that SAFE can be used as a dietary supplement for blood pressure regulation and cardiovascular disease prevention.

Black Soybean and Adzuki Bean Extracts Lower Blood Pressure by Modulating the Renin-Angiotensin System in Spontaneously Hypertensive Rats.

Hypertension, causing cardiovascular disease, stroke, and heart failure, has been a rising health issue worldwide. Black soybeans and adzuki beans have been widely consumed throughout history due to various bioactive components. We evaluated the antihypertensive effects of black soybean and adzuki bean ethanol extracts on blood pressure, renin-angiotensin system (RAS), and aortic lesion in spontaneously hypertensive rats. A group of WKY (normal) and six groups of spontaneously hypertensive rats were administered with saline (SHR), 50 mg/kg of captopril (CAP), 250 and 500 mg/kg of black soybean extracts (BE250 and BE500), 250 and 500 mg/kg of adzuki bean extracts (AE250 and AE500) for eight weeks. BE250, BE500, AE250, and AE500 significantly (p < 0.05) reduced relative liver weight, AST, ALT, triglyceride, total cholesterol, systolic blood pressure, and angiotensin-converting-enzyme level compared to SHR. The angiotensin II level in AE500 and renin mRNA expression in BE500 and AE500 were significantly (p < 0.05) decreased compared to SHR. The lumen diameter was significantly (p < 0.05) reduced in only CAP. Furthermore, systolic and diastolic blood pressure and angiotensin II level in AE500 were lower than those of BE500. These results suggest that AE exhibit more antihypertensive potential than BE in spontaneously hypertensive rats.