Immunomodulatory Effect of Plant-Based Extracts on Neurodegeneration
P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas in Advanced Studies in Experimental and Clinical Medicine, 2021
GB is beneficial for normal cognitive functions due to its proper antioxidant and vascular properties. Presently, in-vitro reports in rats evidenced that a vital mechanism plays a crucial role in reducing BBB permeability by enhancing the cognitive effects of Ginkgolide-B [54]. Moreover, other studies discovered that EGb-761 leaf extract, prevented brain endothelial damage by beta-amyloid oligomer. This oligomer plays a key role in AD pathogenesis [55]. The study was conducted along with 216 patients and they received either a regular dose of 240 mg EGb 761 or placebo. Besides, the clinical efficacy was done by responder analysis along with therapy response defined as response in two of the three primary variables. On the other hand, human studies with GB leaf extract decreased IL-6 levels in serum of patients with neurologic disorders [50]. Furthermore, one week treatment randomized controlled pilot study revealed that a combining effect of Panax ginseng, Ginkgo biloba, and Crocus sativus elevated the working memory in controls [50].
Synthetic DNA-Based Compounds for the Prevention of Coronary Restenosis: Current Status and Future Challenges
Eric Wickstrom in Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Non-sequence-dependent effects are due to the avid binding of negatively charged oligonucleotides (e.g., phosphorothioate) to proteins. The increase in length and concentration of oligomers appears to enhance nonspecific inhibition (Cazenave et al., 1989; Gao et al., 1992; Guvakova et al., 1995). At higher doses oligonucleotides inhibit RNase H activity, thereby eliminating an important mechanism aiding the inhibition of gene expression by antisense. Longer sequences (28-mer) of phosphorothioate homopolymers of cytidine or thymidine have also demonstrated the ability to interact with extracellular growth factors (e.g., bFGF) and their binding with cell surface receptors (Guvakova et al., 1995). This is consistent with their polyanion structure, thereby reducing cell proliferation in non-sequence-dependent manner in vitro and neointimal formation in the rat model in vivo (Guvakova et al., 1995; Wang et al., 1996).
Genetic and Developmental Implications for Trace Metal metabolism from Mutant and Inbred Strains of Animals
Owen M. Rennert, Wai-Yee Chan in Metabolism of Trace Metals in Man, 2017
For possible analogies one should consider the well-demonstrated differences in oxygen-binding properties among the monomeric myoglobins, the hemoglobinopathies, and the tetrameric form of various embryonic, fetal, and adult hemoglobins.130 The ferrodoxins are probably even more relevant to MT.131 These Fe-S metalloproteins are ubiquitously present and serve in electron transport. As with MT they have one or two clusters of cysteine moieties, within a 60 to 80-amino acid chain, each of which serves as the binding site for a covalently linked Fe-S cluster. The ferrodoxins form either monomers and bind two Fe-S clusters, dimers with four Fe-S clusters, or tetramers with eight Fe-S clusters. Although not fully understood, the oligomers appear to have significance for function or for stability.
Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application
Published in Drug Delivery, 2023
Xiaoming Zhong, Jianqiong Yang, Hongyan Liu, Zhiwen Yang, Ping Luo
AmB molecules are divided into three different aggregation states in aqueous media, including monomeric monomers, oligomers or oligo-aggregates, and poly-aggregates (Torrado et al., 2013; Zielińska et al., 2016). Due to its amphiphilic structure and low solubility, AmB tends to aggregate in aqueous solution. AmB monomers exist in water at a very low concentration of 5 × 1 0 −7–1 0 −4 M (Torrado et al., 2013; Zielińska et al., 2016). Above this concentration, AmB molecules occur mostly in the self-aggregated form. Generally, the monomers self-assembled into oligomers or oligo-aggregates form and these into poly-aggregates (Torrado et al., 2013). Oligo-aggregates are usually defined as dimers, even 4 and 8 molecules aggregation of AmB (Zielińska et al., 2016). AmB exhibits four characteristic peaks in the UV absorption spectra i.e., around 407 nm, 385 nm, 365 nm and 344 nm (Torrado et al., 2013; Zielińska et al., 2016). The ratio of the intensity of peak I to peak IV determines the aggregation state of AmB molecules. As reported, the lower ratio of the intensity represents the monomeric state, while its higher ratio confirms molecular aggregates (Thanki et al., 2018).
Effects of water-soluble additive on the release profile and pharmacodynamics of triptorelin loaded in PLGA microspheres
Published in Drug Development and Industrial Pharmacy, 2023
Xiaoyan He, Jiwei Liu, Tao Song, Yiying Sun, Xiaoyan Lu, Nuannuan Li, Kaoxiang Sun
The molecular weight depression of the polymer was determined by the gel permeation chromatography (Figure 8). At the early stage of incubation (the first 3 days), microspheres without additive degraded quickly (F1). For additive containing microspheres, the degradation rate of F2-3, F3-3 and F4-3 was slower but comparable. Water-soluble oligomers were produced while the polymer degraded. The accumulation of acidic oligomers in microspheres will induce autocatalytic degradation of microspheres [13,41]. This will accelerate the degradation of the polymer. Compared with F1, the additive containing microspheres were highly porous (Figure 7). The water-soluble oligomers produced by polymer degradation will be released from the interconnected channels to the release medium. As a result, the autocatalytic degradation of microspheres was inhibited. Hence polymer degradation of F2-3, F3-3 and F4-3 was slower than F1.
Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex
Published in Drug Delivery, 2022
Akula S. N. Murthy, Sanket Das, Tejinder Singh, Tae-Wan Kim, Nasim Sepay, Seob Jeon, Jungkyun Im
Some mitochondria-targeting strategies have been developed in an effort to deliver drugs to mitochondria. They include lipophilic cations, mitochondria-penetrating peptides, and short peptides or oligomers containing guanidines (Fernández-Carneado et al., 2005; Ozawa et al., 2007; Yousif et al., 2009; Szeto & Schiller, 2011; Jean et al., 2014; Kubi et al., 2018). However, lipophilic cations are not effective for delivering large cargoes, and they could have intrinsic toxicity (Murphy & Smith, 2000; Lu et al., 2016). Mitochondria-penetrating peptides are highly prone to hydrolysis by proteases in blood plasma. The toxicity of peptide vehicles having guanidines or cations should be considered as well as their ability to conjugate with drugs. In addition, cell-penetrating peptides, such as HIV-TAT and transportan (which have good cellular internalization and thus attracted interest in preclinical studies) have failed to achieve efficient organelle targeting (Al-Taei et al., 2006; Song et al., 2019). Thus, it is challenging to develop a novel vehicle that can both target mitochondria and deliver drugs that are cell-membrane impermeable.
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