Notes

A great oomycete effector subverts web host vesicle trafficking to station starvation-induced autophagy towards the virus interface.
The"exterior-interior relationship between the lung and the large intestine" is a basic theory in Traditional Chinese Medicine (TCM), which has been confirmed by mounting evidence, and the lung-intestinal axis can be seen as an ex-tension of this theory.Circular RNAs (circRNAs) are a kind of conserved and structurally stable non-coding RNAs, which have been found to be differentially expressed and associated with the development of cancer in malignant tumors.Many studies have found that circRNAs play an important role in the lung and intestinal cancers. This review focuses on circRNAs and reveals that there are common circRNAs that are both highly or poorly expressed in lung-intestinal axis cancers and most of them regulate the proliferation, migration,and invasion of cancer cells by sponging miRNAs. These results not only provide new evidences and research ideas for the "exterior-interior relationship between the lung and the large intestine", but also suggests that circRNAs can be new potential therapeutic targets for the future drug research of lung-intestinal axis diseases.The unmet need for the development of effective drugs to treat Alzheimer's disease has been steadily growing, representing a major challenge in drug discovery. In this context, drug repurposing, namely the identification of novel therapeutic indications for approved or investigational compounds, can be seen as an attractive attempt to obtain new medications reducing both the time and the economic burden usually required for research and development programs. In the last years, several classes of drugs have evidenced promising beneficial effects in neurodegenerative diseases, and for some of them preliminary clinical trials have been started. This review aims to illustrate some of the most recent examples of drugs reprofiled for Alzheimer's disease, considering not only the finding of new uses for existing drugs, but also the new hypotheses on disease pathogenesis, that could promote previously unconsidered therapeutic regimens. Moreover, some examples of structural modifications performed on existing drugs in order to obtain multifunctional compounds will also be described.The most typical feature of atherogenesis in humans at its early stage is the formation of foam cells in subendothelial arterial intima, which occurs as the consequence of intracellular cholesterol deposition. The main source of lipids accumulating in the arterial wall are circulating low-density lipoprotein (LDL). However, LDL particles should undergo proatherogenic modification to acquire atherogenic properties. One of the known types of atherogenic modification of LDL is enzymatic deglycosilation, namely, desialylation, which is the earliest change in the cascade of following multiple LDL modifications. The accumulating data make sialidases an intriguing and plausible therapeutic target, since pharmacological modulation of activity of these enzymes may have beneficial effects in several pathologies, including atherosclerosis. The hypothesis exists that decreasing LDL enzymatic desialylation may result in prevention of lipid accumulation in arterial wall, thus breaking down one of the key players in atherogenesis at the cellular level. BAY-293 in vitro Several drugs acting as glycomimetics and inhibiting sialidase enzymatic activity already exist, but the concept of sialidase inhibition as an anti-atherosclerosis strategy remains unexplored to date. This review is focused on the potential possibilities of the repurposing of sialidase inhibitors for pathogenetic anti-atherosclerotic therapy.Glycosphingolipids (GSLs) are ubiquitous components on animal cell membranes, and exposed on the outer surface. Various studies have demonstrated that they play key roles in cells proliferation, adhesion, motility and differentiation. Usually, the specific types of GSLs are expressed more highly in tumors than in normal tissues, which are known as tumorassociated antigens. It has been revealed that most tumor cells show altered GSLs patterns on their surface, abnormal GSLs signaling and biosynthesis, which together play a major role in tumor development. Tumor-associated GSL antigens have been used in the development of antitumor vaccines. It is no doubt that GSLs play a crucial role in tumor progression and would be a promising target for cancer treatment.Administration of substances through the skin represents a promising alternative, in relation to others drug administration routes, due to its large body surface area, in order to offer ideal and multiple sites for drug administration. In addition, the administration of drugs through the skin avoids first-pass metabolism, allowing an increase in the bioavailability of drugs, as well as reducing their side effects. However, the stratum corneum (SC) comprises the main barrier of protection against external agents, mainly due to its structure, composition and physicochemical properties, becoming the main limitation for the administration of substances through the skin. In view of the above, pharmaceutical technology has allowed the development of multiple drug delivery systems (DDS), which include liquid crystals (LC), cubosomes, liposomes, polymeric nanoparticles (PNP), nanoemulsions (NE), as well as cyclodextrins (CD) and dendrimers (DND). It appears that the DDS circumvents the problems of drug absorption through the SC layer of the skin, ensuring the release of the drug, as well as optimizing the therapeutic effect local. This review aims to highlight the DDS that include LC, cubosomes, lipid systems, PNP, as well as CD and DND, to optimize topical skin therapies.Complex common diseases are a significant burden for our societies and demand not only preventive measures but also more effective, safer, and more affordable treatments. The whole process of the current model of drug discovery and development implies a high investment by the pharmaceutical industry, which ultimately impact in high drug prices. In this sense, drug repurposing would help meet the needs of patients to access useful and novel treatments. Unlike the traditional approach, drug repurposing enters both the preclinical evaluation and clinical trials of the compound of interest faster, budgeting research and development costs, and limiting potential biosafety risks. The participation of government, society, and private investors is needed to secure the funds for experimental design and clinical development of repurposing candidates to have affordable, effective, and safe repurposed drugs. Moreover, extensive advertising of repurposing as a concept in the health community, could reduce prescribing bias when enough clinical evidence exists, which will support the employment of cheaper and more accessible repurposed compounds for common conditions.
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