Continuous measurement of proteins in vivo is important for real-time disease management and prevention. Implantable sensors for monitoring small molecules such as glucose have been available for more than a decade. However, analysis of proteins remains an unmet need because the lower physiological levels require that sensors have high affinities, which are linked to long complexation half-lives ( t _1/2 ~20 hours) and slow equilibration when concentrations decrease. We report active-reset sensors by use of high-frequency oscillations to accelerate dissociation, which enables regeneration of the unbound form of the sensor within 1 minute. When implemented within implanted devices, these sensors allow for real-time, in vivo monitoring of proteins within interstitial fluid. Active-reset protein sensors track biomarker levels on a physiological timescale for inflammation monitoring in living animals.

Pancreatic lipase (PL) is a key enzyme for the degradation of triglycerides absorbed in the diet and it is involved in several pathologies, such as acute pancreatitis, an inflammatory state of the pancreas. In this work we performed the virtual screening of a tripeptide library, with the aim to discover novel lead compounds as inhibitors of human PL. The 9 top-ranked peptides were synthesized by solid phase peptide synthesis and tested in vitro. Among them, peptides M5 and M7 were found to be the most potent inhibitors of the series, validating our method as a useful strategy to discover peptide inhibitors.

A transdermal patch that delivers insulin at high glucose concentrations can offer tremendous advantages to ease the concern of safety and improve the quality of life for people with diabetes. Herein, a novel self‐crosslinkable and glucose‐responsive polymer‐based microneedle patch (MN) is designed to deliver insulin at hyperglycemia. The microneedle patch is made of hyaluronic acid polymers functionalized with dopamine and 4‐amino‐3‐fluorophenylboronic acid (AFBA) that can be quickly crosslinked upon mixing of the polymer solutions in the absence of any chemicalcrosslinking agents or organic solvents. The catechol groups in the dopamine (DA) units form covalent crosslinkages among themselves by auto‐oxidation and dynamic crosslink with phenylboronic acid (PBA) via complexation. The reversible crosslinkages between catechol and boronate decrease with increasing glucose concentration leading to higher swelling and faster insulin release at hyperglycemia as compared to euglycemia. Such superior glucose‐responsive properties are demonstrated by in vitro analyses and in vivo efficacy studies. The hydrogel polymers also preserve native structure and bioactivity of insulin, attributable to the interaction of hyaluronic acid (HA) with insulin molecules, as revealed by experiments and molecular dynamics simulations. The simplicity in the design and fabrication process, and glucose‐responsiveness in insulin delivery impart the matrix microneedle (mMN) patch great potential for clinical translation.

The endocannabinoid system is activated by the binding of natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) as lipophilic messengers to cannabinoid receptors CB1 and CB2. The endocannabinoid system comprises also many hydrolytic enzymes responsible for the endocannabinoids cleavage, such as FAAH and MAGL. These two enzymes are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently a new family of endocannabinoid modulators was discovered; the lead of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1. Hemopressin shows several physiological effects, e.g. antinociception, hypophagy, and hypotension. It is still matter of debate whether this peptide, isolated from the brain of rats is a real neuromodulator of the endocannabinoid system. Recent evidence indicates that hemopressin could be a by-product formed by chemical degradation of a longer peptide RVD-hemopressin during the extraction from the brain homolysate. Indeed, RVD-hemopressin is more active than hemopressin in certain biological tests and may bind to the same subsite as Rimonabant, which is an inverse agonist for the CB1 receptor and a μ-opioid receptor antagonist. These findings have stimulated several studies to verify this hypothesis and to evaluate possible therapeutic applications of hemopressin, its peptidic derivatives and synthetic analogues, opening new perspectives to the development of novel cannabinoid drugs.

Background: In recent years, the multi-drug resistance of bacteria and fungi strains has become a worldwide problem. The incidence of fungal and bacterial infections is experiencing a serious growth and the microorganisms have developed several new mechanisms of antibiotic resistance. Methods: Antimicrobial peptides (AMPs) constitute one of the well-known barrier defense systems of plants. They have been isolated from roots, seeds, flowers, stems and leaves of a wide variety of species and have activities towards phytopathogens, as well as against human pathogens. AMPs are often cationic peptides able to interact with the membrane through penetration or dissolving the biofilms. Results and Conclusion: In this paper, we report the synthesis of several arginine and lysine-rich peptides and their evaluation as antimicrobial agents.