Bioelectrochemistry for various facets of tau protein biochemistry

Tau protein undergoes complex biochemical processes involved in normal and diseased cellular functions; specifically, tau pathology has been linked to neurodegeneration. At the heart of tau biochemistry are three pillars: microtubules, phosphorylation, and aggregation. However, these three processes are also regulated through other biomolecules in the biological setting, such as metal ions and small and larger ligands, including proteins and nucleic acids. This review describes the latest electrochemical approaches toward greater understanding of tau biochemistry, early disease diagnosis, and drug inhibitor screening.     

Tendon-bone junction healing by injectable bioactive thermo-sensitive hydrogel based on inspiration of tendon-derived stem cells

The rotator cuff repaired construct must establish a contiguous and functioning tendon-bone junction to provide adequate stability. However, fibrocartilage deficiency and bone loss were hardly reversed after physical suture, especially in chronic rotator cuff tears. In this study, we synthesized an injectable methylcellulose/polyvinyl alcohol/polyvinylpyrrolidone-based thermo-sensitive hydrogel, which delivered kartogenin-loaded mesoporous bioactive glass nanoparticles. Physicochemical studies the revealed phase transition temperatures of 35 °C and its ability to induce chondrogenesis and osteogenesis differentiation of tendon-derived stem cells. Furthermore, experiments in rabbit chronic rotator cuff tears model confirmed the fibrocartilage and bone layer regenerative capability of the injected bioactive hydrogel, which could, in turn, support the ultimate tensile stress of the repaired rotator cuff. The bioactive agents-loaded hydrogel reported in this study is a valuable addition to the arsenal of biomaterials in applications to chronic tendon-bone junction injuries.     

Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray–Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.     

Nanochaperone‐Based Strategies to Control Protein Aggregation Linked to Conformational Diseases

The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, including primarily neurodegenerative diseases. Such disorders are characterized by misfolded proteins that lose their normal physiological roles and acquire toxicity. Recent findings suggest that proteostasis network impairment may be one of the causes leading to the accumulation and spread of amyloids. These observations are certainly contributing to a new focus in anti‐amyloid drug design, whose efforts are so far being centered on single‐target approaches aimed at inhibiting amyloid aggregation. Chaperones, known to maintain proteostasis, hence represent interesting targets for the development of novel therapeutics owing to their potential protective role against protein misfolding diseases. In this minireview, research on nanoparticles that can either emulate or help molecular chaperones in recognizing and/or correcting protein misfolding is discussed. The nascent concept of “nanochaperone” may indeed set future directions towards the development of cost‐effective, disease‐modifying drugs to treat several currently fatal disorders.     

Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

Extract from the Marine Seaweed Padina pavonica Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides

The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive compounds to protect mitochondrial membranes against insult by oligomeric aggregates of the amyloidogenic proteins amyloid-β (Aβ), α-synuclein (α-syn) and tau, which are currently considered to be major targets for drug discovery in Alzheimer’s disease (AD) and Parkinson’s disease (PD). We show that PPE manifested a significant inhibitory effect against swelling of isolated mitochondria exposed to the amyloid oligomers, and attenuated the release of cytochrome c from the mitochondria. Using cardiolipin-enriched synthetic lipid membranes, we also show that dye leakage from fluorophore-loaded vesicles and formation of channel-like pores in planar bilayer membranes are largely prevented by incubating the oligomeric aggregates with PPE. Lastly, we demonstrate that PPE curtails the ability of Aβ42 and α-syn monomers to self-assemble into larger β-aggregate structures, as well as potently disrupts their respective amyloid fibrils. In conclusion, the mito-protective and anti-aggregator biological activities of Padina pavonica extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD.     

Impact of Matrix Metalloproteinase-9 during Periodontitis and Cardiovascular Diseases

Matrix metalloproteinase-9 (MMP-9) has been shown to play a key role in endothelial function and perhaps pivotal in the correlation between periodontal disease and cardiovascular disease (CVD). For the study, the impact of MMP-9 of periodontitis and CVD on serum and saliva concentrations was analyzed. For the study patients with periodontitis (n = 31), CVD (n = 31), periodontitis + CVD (n = 31), and healthy patients (n = 31) were enrolled. Clinical and demographic characteristics as well as serum and salivary MMP-9 were evaluated. MMP-9 concentrations in serum and saliva were statistically elevated in patients with CVD (p < 0.01) and in patients with periodontitis plus CVD (p < 0.001) compared to patients with periodontitis and healthy subjects. Multivariate regression analysis showed that c-reactive protein (hs-CRP) was the only significant predictor for MMP-9 serum (p < 0.001), whereas hs-CRP (p < 0.001) and total cholesterol (p = 0.029) were the statistically significant salivary MMP-9 predictors. This study evidenced that patients with CVD and periodontitis + CVD presented elevated MMP-9 concentrations in serum and saliva compared to patients with periodontitis and healthy subjects. Furthermore, hs-CRP was a negative predictor of serum and salivary MMP-9.     

Kaempferia parviflora Extract Alleviated Rat Arthritis,Exerted Chondroprotective Properties In Vitro,and Reduced Expression of Genes Associated with Inflammatory Arthritis

Kaempferia parviflora Wall. ex Baker (KP) has been reported to attenuate cartilage destruction in rat model of osteoarthritis. Previously, we demonstrated that KP rhizome extract and its active components effectively suppressed mechanisms associated with RA in SW982 cells. Here, we further evaluated the anti-arthritis potential of KP extract by using multi-level models, including a complete Freund’s adjuvant-induced arthritis and a cartilage explant culture model, and to investigate the effects of KP extract and its major components on related gene expressions and underlying mechanisms within cells. In arthritis rats, the KP extract reduced arthritis indexes, with no significant changes in biological parameters. In the cartilage explant model, the KP extract exerted chondroprotective potential by suppressing sulfated glycosaminoglycans release while preserving high accumulation of proteoglycans. In human chondrocyte cell line, a mixture of the major components equal to their amounts in KP extract showed strong suppression the expression of genes-associated inflammatory joint disease similar to that of the extract. Additionally, KP extract significantly suppressed NF-κB and MAPK signaling pathways. The suppressing expression of necroptosis genes and promoted anti-apoptosis were also found. Collectively, these results provided supportive evidence of the anti-arthritis properties of KP extract, which are associated with its three major components.     

Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.     

Role of Gut Microbiota,Probiotics and Prebiotics in the Cardiovascular Diseases

In recent years, there has been a growing interest in identifying and applying new, naturally occurring molecules that promote health. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host”. Quite a few fermented products serve as the source of probiotic strains, with many factors influencing the effectiveness of probiotics, including interactions of probiotic bacteria with the host’s microbiome. Prebiotics contain no microorganisms, only substances which stimulate their growth. Prebiotics can be obtained from various sources, including breast milk, soybeans, and raw oats, however, the most popular prebiotics are the oligosaccharides contained in plants. Recent research increasingly claims that probiotics and prebiotics alleviate many disorders related to the immune system, cancer metastasis, type 2 diabetes, and obesity. However, little is known about the role of these supplements as important dietary components in preventing or treating cardiovascular disease. Still, some reports and clinical studies were conducted, offering new ways of treatment. Therefore, the aim of this review is to discuss the roles of gut microbiota, probiotics, and prebiotics interventions in the prevention and treatment of cardiovascular disease.