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Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This administration route is however associated with limited patient’s compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.

The objective of this review is to list the structures composed of a pyridopyrimidine moiety which have shown a therapeutic interest or have already been approved for use as therapeutics. We consider all the synthetic protocols to prepare these pyridopyrimidine derivatives. The review is organized into four sections, successively pyrido[2,3-d]pyrimidines, pyrido[3,4-d]pyrimidines, pyrido[4,3-d]pyrimidines and pyrido[3,2-d]pyrimidines. For each compound we present the biological activity and the synthetic route reported. To produce this manuscript, the bibliographic research was done using Reaxys and Scifinder for each kind of pyridopyrimidine.

Eucalyptus plants have attracted the attention of researchers and environmentalists worldwide because they are a rapidly growing source of wood and a source of oil used for multiple purposes. The main and the most important oil component is 1,8-cineole (eucalyptol: 60–85%). This review summarizes the literature reported to date involving the use of 1,8-cineole for the treatment of disorders. Additionally, we describe our efforts in the use of eucalyptol as a solvent for the synthesis of O,S,N-heterocycles. Solvents used in chemistry are a fundamental element of the environmental performance of processes in corporate and academic laboratories. Their influence on costs, safety and health cannot be neglected. Green solvents such as bio-based systems hold considerable additional promise to reduce the environmental impact of organic chemistry. The first section outlines the process leading to our discovery of an unprecedented solvent and its validation in the first coupling reactions. This section continues with the description of its properties and characteristics and its reuse as reported in the various studies conducted. The second section highlights the use of eucalyptol in a series of coupling reactions (i.e., Suzuki–Miyaura, Sonogashira–Hagihara, Buchwald–Hartwig, Migita–Kosugi–Stille, Hiyama and cyanation) that form O,S,N-heterocycles. We describe the optimization process applied to reach the ideal conditions. We also show that eucalyptol can be a good alternative to build heterocycles that contain oxygen, sulfur and nitrogen. These studies allowed us to demonstrate the viability and potential that bio solvents can have in synthesis laboratories.

The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs) 1 , 2 . However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage 3 , 4 – 5 . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα) + fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα + population: FAPα + THY1 + immune effector fibroblasts located in the synovial sub-lining, and FAPα + THY1 − destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα + THY1 − fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα + THY1 + fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage. Distinct subsets of fibroblasts, which differ in their expression of thymus cell antigen 1 (THY1), are responsible for inflammation and tissue damage in mouse models of arthritis.

Large-scale production of microalgae and their bioactive compounds has steadily increased in response to global demand for natural compounds. Spirulina, in particular, has been used due to its high nutritional value, especially its high protein content. Promising biological functions have been associated with Spirulina extracts, mainly related to its high value added blue pigment, phycocyanin. Phycocyanin is used in several industries such as food, cosmetics, and pharmaceuticals, which increases its market value. Due to the worldwide interest and the need to replace synthetic compounds with natural ones, efforts have been made to optimize large-scale production processes and maintain phycocyanin stability, which is a highly unstable protein. The aim of this review is to update the scientific knowledge on phycocyanin applications and to describe the reported production, extraction, and purification methods, including the main physical and chemical parameters that may affect the purity, recovery, and stability of phycocyanin. By implementing different techniques such as complete cell disruption, extraction at temperatures below 45 °C and a pH of 5.5–6.0, purification through ammonium sulfate, and filtration and chromatography, both the purity and stability of phycocyanin have been significantly improved. Moreover, the use of saccharides, crosslinkers, or natural polymers as preservatives has contributed to the increased market value of phycocyanin.

The solvents used in chemistry are a fundamental element of the environmental performance of processes in corporate and academic laboratories. Their influence on costs, health safety, and nature cannot be neglected. Quantitatively, solvents are the most abundant constituents of chemical transformations; therefore, acting on solvents and replacing standard solvents with safer products can have a great ecological impact. However, not all green solvents are suitable for the wide scope of organic chemistry reactions. A second point to consider is that 50% of pharmaceutical drugs are nitrogen heterocycles compounds. It therefore appeared important to provide an overview of the more ecological methodologies for synthesizing this class of compounds. In this review, all publications since 2000 that describe green reactions leading to the formation of nitrogen heterocycles using safe solvents were considered. We chose water, PEG, and bio-based solvents for their negligible toxicity. The synthesis of five-, six-, and seven-membered aromatic nitrogen heterocycles using green reactions reported in the literature to date is described.

The development of new and greener approaches to organic synthesis has been a trend in recent years. Continuing the latest publications of our team, in this work, we demonstrate the efficiency of three solvents: eucalyptol (1,8-cineole), cyclopentyl methyl ether (CPME), and 2-methyltetrahydrofuran (2-MeTHF) for the synthesis of O,S,N-heterocyclic compounds.

Timber–concrete composite (TCC) structural systems are characterized by the combination of timber and concrete, which are connected to transmit shear forces between the two elements. In addition, to achieve an efficient connection, the slip between the two materials should be limited. Therefore, the load-carrying capacity, the stiffness, and the failure mode of TCC connections are important for the behavior of the composite element. This work aims to investigate the influence of test conditions on TCC connections using shear tests to determine the mechanical properties of connections. Therefore, it is essential to understand the influence of the configuration of the specimens (symmetric as push-out tests or asymmetric as inclined tests), the type of interface between the timber and concrete, and the test procedure (static or cyclic load protocol) on the resulting load-carrying capacity, stiffness, and failure modes. This paper reviews experimental tests conducted on TCC shear connection specimens, using various configurations to assess the influence of the test specimen configuration, material interface, and testing protocol on the determination of the mechanical properties.

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

We report here the use of eucalyptol as a bio-based solvent for Hiyama coupling, cyanation, and multicomponent reactions on O,S,N-heterocycles. These heterocycles were chosen as targets or as starting materials given their biological potential; they play an important role in therapeutically active compounds. Once again, eucalyptol proved to be a credible and sustainable alternative to common solvents.