Chemical Bonding by the Chemical Orthogonal Space of Reactivity

The fashionable Parr–Pearson (PP) atoms-in-molecule/bonding (AIM/AIB) approach for determining the exchanged charge necessary for acquiring an equalized electronegativity within a chemical bond is refined and generalized here by introducing the concepts of chemical power within the chemical orthogonal space (COS) in terms of electronegativity and chemical hardness. Electronegativity and chemical hardness are conceptually orthogonal, since there are opposite tendencies in bonding, i.e., reactivity vs. stability or the HOMO-LUMO middy level vs. the HOMO-LUMO interval (gap). Thus, atoms-in-molecule/bond electronegativity and chemical hardness are provided for in orthogonal space (COS), along with a generalized analytical expression of the exchanged electrons in bonding. Moreover, the present formalism surpasses the earlier Parr–Pearson limitation to the context of hetero-bonding molecules so as to also include the important case of covalent homo-bonding. The connections of the present COS analysis with PP formalism is analytically revealed, while a numerical illustration regarding the patterning and fragmentation of chemical benchmarking bondings is also presented and fundamental open questions are critically discussed.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。