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COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

INTRODUCTION: Diabetes mellitus (DM) is the most common metabolic disease and multifactorial, harming patients worldwide. Extensive research has been carried out in the search for novel drug delivery systems offering reliable control of glucose levels for diabetics, aiming at efficient management of DM. AREAS COVERED: Polymeric micelles (PMs) as smart drug delivery nanocarriers are discussed, focusing on oral drug delivery applications for the management of hyperglycaemia. The most recent approaches used for the preparation of smart PMs employ molecular features of amphiphilic block copolymers (ABCs), such as stimulus sensitivity, ligand conjugation, and as a more specific example the ability to inhibit islet amyloidosis. EXPERT OPINION: PMs provide a unique platform for self-regulated or spatiotemporal drug delivery, mimicking the working mode of pancreatic islets to maintain glucose homeostasis for prolonged periods. This unique characteristic is achieved by tailoring the functional chemistry of ABCs considering the physicochemical traits of PMs, including sensing capabilities, hydrophobicity etc. In addition, the application of ABCs for the inhibition of conformational changes in islet amyloid polypeptide garnered attention as one of the root causes of DM. However, research in this field is limited and further studies at the clinical level are required.

Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

Synbiotics, are a combination of probiotics and prebiotics. They play an important role in metabolizing different nutritional substrates and thus helps in the maintenance of human health. Any disbalance in the gut microflora, known as dysbiosis, is known to lead to a number of diseased conditions. It can be reverted by the administration of synbiotics. Present review highlights various mechanistic pathways through which synbiotics act as therapeutics. The dual role of synbiotics as nutraceutical and excipient in developing oral formulations are entailed with case studies. The findings entailed that there exist numerous studies on prebiotics as well as probiotics have been carried out to show their effects in several diseases. However, the concept of combining together them for prevention and treatment of various pathological conditions accruing from dysbiosis is relatively new. Synbiotics, however, face challenge of low stability during their sojourn in the GIT, which is generally overcome by various encapsulation techniques. Various studies also showed potential role of synbiotics in drug delivery. However, it is an emerging area and lacks clinical correlation. It is important to focus on clinical trials of formulations wherein synbiotics have been used as therapeutic moiety as well as pharmaceutical carrier for treating various diseases.

Publisher Copyright: © 2022 The Author(s). Published by IMR Press. Computational approaches to study of neuronal impairment is rapidly evolving, as experiments and intuition alone do not explain the complexity of the brain system. An overwhelming increase in the amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals is imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. This review seeks to outline the biological databases and analytical tools along with their applications. It is envisaged that such knowledge could provide a ''training recipe'' for young scientists and a guide for professionals and researchers in neuroscience.

Mucus gel constitutes of heavily cross-linked mucin fibers forming a viscoelastic, dense porous network that coats all the exposed epithelia not covered with the skin. The layer provides protection to the underlying gastrointestinal, respiratory, and female reproductive tracts, in addition to the organs such as the surface of eye by trapping the pathogens, irritants, environmental fine particles, and potentially hazardous foreign matter. However, this property of mucus gel poses a substantial challenge for realizing the localized and sustained drug delivery across the mucosal surfaces. The mucus permeating particles that spare the protective properties of mucus gel improve the therapeutic potency of the drugs aimed at the management of diseases, including sexually transmitted infections, lung cancer, irritable bowel disease, degenerative eye diseases and infections, and cystic fibrosis. As such, the mucoadhesive materials conjugated with drug molecules display a prolonged retention time in the mucosal gel that imparts a sustained release of the deliberated drug molecules across the mucosa. The contemporarily developed mucus penetrating materials for drug delivery applications comprise of a finer size, appreciable hydrophilicity, and a neutral surface to escape the entrapment within the cross-inked mucus fibers. Pertaining to the mucus secretion as a first line of defence in respiratory tract in response to the invading physical, chemical, and biological pathogens, the development of mucus penetrating materials hold promise as a stalwart approach for revolutionizing the respiratory drug delivery paradigm. The present review provides an epigrammatic collation of the mucus penetrating/mucoadhesive materials for achieving a controlled/sustained release of the cargo pharmaceutics and drug molecules across the respiratory mucus barrier.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world and it is becoming one of the most frequent cause of liver transplantation. Unfortunately, the only available method that can reliably determine the stage of this disease is liver biopsy, however, it is invasive and risky for patients. The purpose of this study is to investigate changes in the intracellular composition of the liver fatty acids during the progression of the NAFLD in a mouse model fed with Western diet, with the aim of identify non-invasive biomarkers of NAFLD progression based in

A simple and inexpensive method is required to assess fatty infiltration of the liver non-invasively.To develop and compare different methods to quantify liver fat by magnetic resonance and compare it against ultrasound.Three algorithms were implemented: region growing (RG), graph cuts (GC) and hierarchical (HR), all based on the IDEAL method to obtain water and fat images. Using these images, the proton density fat fraction (PDFF) was calculated. The three methods were tested in phantoms with known fat percentages and later on we acquired images from 20 volunteers with an ultrasound diagnosis of fatty liver disease in different stages. For everyone, the PDFF of the nine liver segments was determined.In phantoms, the mean error between the real fat percentage and the value obtained through the three methods was -1,26, -1 and -0,8 for RG, GC and HR, respectively. The hierarchical method was more precise and efficient to obtain PDFF. The results in volunteers revealed that ultrasound showed errors categorizing the severity of hepatic steatosis in more than 50% of volunteers.We developed a tool for magnetic resonance, which allows to quantify fat in the liver. This method is less operator dependent than ultrasound and describes the heterogeneity in the fat distribution along the nine hepatic segments.

We describe an efficient convergent synthesis of vitamin D

The authors thank the Spanish Ministerio de Ciencia e Innovacion (MICINN) (grant numbers CTQ2007-65218, Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (PROMETEO/2009/039), the Fondos Europeos para el Desarrollo Regional (FEDER)) and the University of Alicante for financial support.

Satellite cells are a small cell population that function as muscle-specific adult stem cells. When muscle damage occurs, these cells are able to activate, proliferate, and ultimately fuse with each other in order to form new myofibers or fuse with existing ones. For tissue engineering applications, obtaining a sufficient number of myoblasts prior transplantation that maintains their regenerative capacity is critical. This can be obtained by in vitro expansion of autologous satellite cells. However, once plated, the self-renewal and regenerative capacity of myoblasts is rapidly lost, obtaining low yields per biopsy. For this purpose, we evaluated in vitro culture of the murine myoblast cell line C2C12 and mouse primary myoblasts with chitosan and chitosan/poly-octanoic acid 2-thiophen-3-yl-ethyl ester blends (poly(OTE)). The films of chitosan/poly(OTE) blends were heterogeneous and slightly rougher than chitosan and poly(OTE) films. Poly(OTE) presence improved myoblast adhesion in both cell types and prevented complete differentiation, but maintaining their differentiation potential in vitro. We identified that the polymer blend chitosan/poly(OTE) could be a suitable substrate to culture satellite cells/myoblasts in vitro preventing differentiation prior transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 118-130, 2017.

Structure-guided optimization was used to design new analogues of 1α,25-dihydroxyvitamin D3 bearing the main side chain at C12 and a shorter second hydroxylated chain at C17. The new compounds 5a–c were efficiently synthesized from ketone 9 (which is readily accessible from the Inhoffen–Lythgoe diol) with overall yields of 15%, 6%, and 3% for 5a, 5b, and 5c, respectively. The triene system was introduced by the Pd-catalyzed tandem cyclization–Suzuki coupling method. The new analogues were assayed against human colon and breast cancer cell lines and in mice. All new vitamin D3 analogues bound less strongly to the VDR than 1α,25-dihydroxyvitamin D3 but had similar antiproliferative, pro-differentiating, and transcriptional activity as the native hormone. In vivo, the three analogues had markedly low calcemic effects. © 2012 American Chemical Society., We thank the Spanish Ministry of Education and Innovation (SAF2007-67205 and SAF2010-15291 to A. Mouriño, SAF2010-18302 to A. Muñoz, and SAF2009-07631 to RPF) for financial support.

The authors thank the Spanish Ministerio de Ciencia e Innovacion (MICINN) (grant numbers CTQ2007-65218, Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (PROMETEO/2009/039), the Fondos Europeos para el Desarrollo Regional (FEDER)) and the University of Alicante for financial support.

Structure-guided optimization was used to design new analogues of 1α,25-dihydroxyvitamin D₃ bearing the main side chain at C12 and a shorter second hydroxylated chain at C17. The new compounds 5a-c were efficiently synthesized from ketone 9 (which is readily accessible from the Inhoffen-Lythgoe diol) with overall yields of 15%, 6%, and 3% for 5a, 5b, and 5c, respectively. The triene system was introduced by the Pd-catalyzed tandem cyclization-Suzuki coupling method. The new analogues were assayed against human colon and breast cancer cell lines and in mice. All new vitamin D₃ analogues bound less strongly to the VDR than 1α,25-dihydroxyvitamin D₃ but had similar antiproliferative, pro-differentiating, and transcriptional activity as the native hormone. In vivo, the three analogues had markedly low calcemic effects.

Based on the crystal structures of human vitamin D receptor (hVDR) bound to 1α,25-dihydroxy-vitamin D 3 (1,25 D) and superagonist ligands, we previously designed new superagonist ligands with a tetrahydrofuran ring at the side chain that optimize the aliphatic side-chain conformation through an entropy benefit. Following a similar strategy, four novel vitamin D analogues with aromatic furan side chains (3 a, 3 b, 4 a, 4 b) have now been developed. The triene system has been constructed by an efficient stereoselective intramolecular cyclization of an enol triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the resulting intermediate with an alkenyl boronic ester (CD-side chain, upper fragment). The furan side chains have been constructed by gold chemistry. These analogues exhibit significant pro-differentiation effects and transactivation potency. The crystal structure of 3 a in a complex with the ligand-binding domain of hVDR revealed that the side-chain furanic ring adopts two conformations. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., We thank the Spanish Ministry of Education and Innovation (MEI) (projects SAF2007–67205, SAF2010–15291, and SAF2010–18302) and the “Red Tem ática de Investigaci n Cooperativa en Cá ncer” (ISCIII, RD06/0020/0009) for financial support.