Disrupting GPCR Complexes with Smart Drug-like Peptides

G protein-coupled receptors (GPCRs) are a superfamily of proteins classically described as monomeric transmembrane (TM) receptors. However, increasing evidence indicates that many GPCRs form higher-order assemblies made up of monomers pertaining to identical (homo) or to various (hetero) receptors. The formation and structure of these oligomers, their physiological role and possible therapeutic applications raise a variety of issues that are currently being actively explored. In this context, synthetic peptides derived from TM domains stand out as powerful tools that can be predictably targeted to disrupt GPCR oligomers, especially at the interface level, eventually impairing their action. However, despite such potential, TM-derived, GPCR-disrupting peptides often suffer from inadequate pharmacokinetic properties, such as low bioavailability, a short half-life or rapid clearance, which put into question their therapeutic relevance and promise. In this review, we provide a comprehensive overview of GPCR complexes, with an emphasis on current studies using GPCR-disrupting peptides mimicking TM domains involved in multimerization, and we also highlight recent strategies used to achieve drug-like versions of such TM peptide candidates for therapeutic application.

The Mechanism of Stem Cell Aging

Stem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.

Application of Nanoemulsion in Cancer Treatment

Nanoemulsions are pharmaceutical-based nanometres ranged nanoformulated particles with significant and valuable contribution in field of the nanotechnology. In cancer treatment, the treatment through drugs fails primarily due to multidrug resistance (MDR), poor solubility, and unspecific toxicity. Nanoemulsions have the remarkable properties of non-immunogenicity, biodegradability, sustained encapsulation of low water solubility drugs, sustained regulated release of drug, stable and safe carrying tendency to deliver such drugs, and specificity in targeting only cancer cells to overcome multidrug resistance through for clinical and therapeutic application. They excellently address the noncompliance issues associated with the conventional anti-cancerous chemotherapeutic dosage issues. Currently multifunctional nanoemulsions are under experimentation for the treatment of various types of cancer. The chapter highlights the current status and applications of nanoemulsions as anti-cancer therapeutics and their commercial importance.

Homeopathic use of modern drugs: therapeutic application of the organism paradoxical reaction or rebound effect

When Samuel Hahnemann systematized homeopathy and the effects of drugs on the state of human health, he described the primary action of drugs and the following secondary and opposite reaction of the organism. Seeking to apply this secondary action or vital reaction of the organism as therapeutic method, he postulated the principle of similitude, i.e. the prescription to ill individuals of drugs that cause similar symptoms in the healthy (similia similibus curentur). In modern pharmacology, secondary action (vital reaction) of drugs is known as rebound effect or paradoxical reaction of the organism. It has been observed after discontinuation of several classes of palliative (enantiopathic) drugs, namely those that act according to the principle of contraries (contraria contrariis curentur). Although in this case it is associated with severe and fatal iatrogenic events, rebound effect might awaken a healing reaction when the very same drug is employed according to the principle of similitude. The validity of the principle of similitude is proved by scientific evidence on rebound effect, whereas conventional drugs primary (therapeutic, adverse and side) effects might be equated to pathogenetic manifestations and thus be homeopathically applied. For this purpose a homeopathic materia medica and repertory comprising 1,251 modern drugs was elaborated using the monographs described in The United States Pharmacopeia Dispensing Information as source (www.newhomeopathicmedicines.com). Thus, the therapeutic range of homeopathy is broadened through the addition of hundreds of new medicines that might be employed in every kind of disease including countless modern clinical syndromes.

Comparative Pharmaceutical and Analytical Study of Chapal Shodhan (Purification Process) with Special Reference to Bismuth and Selenium

Rasashastra is the branch of science which deals with alchemic preparation or metal and mineral medicinal formulation explained in ancient texts of Ayurved. Rasashastra explained group of drugs in different names on the basis their therapeutic application and binding capacity of drug with Mercury. Chapal one among the group of Maharasa which is having potent therapeutic properties like immune modulator, analgesic, rejuvenator and aphrodisiac. Due to lack of identification, difficulty in procurement and confusion in synonyms and vernacular names, Chapal placed in controversial drugs. Some opines Chapal as Bismuth and some says Selenium. To overcome from these controversies to confirm the type of drug this comparative study is undertaken. Comparative study given nearer conclusion that Chapal can be Selenium, after observing organoleptic properties and symptoms experienced by the person during the purificatory process.

Interventional cardiologists’ attitudes towards pharmacogenetic testing and impact on antiplatelet prescribing decisions

Aim: To determine if interventional cardiologists’ knowledge and attitudes toward pharmacogenetic (PGx) testing influenced their antiplatelet prescribing decisions in response to CYP2C19 results. Materials & methods: Surveys were administered prior to participating in a randomized trial of CYP2C19 testing. Associations between baseline knowledge/attitudes and agreement with the genotype-guided antiplatelet recommendations were determined using multivariable logistic regression. Results: 50% believed that PGx testing would be valuable to predict medication toxicity or efficacy. 64% felt well informed about PGx testing and its therapeutic application. However, PGx experience, knowledge, nor attitudes were significantly associated with agreement to genotype-guided antiplatelet recommendations. Conclusion: Cardiologists’ knowledge and attitudes were not associated with CYP2C19-guided antiplatelet prescribing, but larger studies should be done to confirm this finding.

Neutrophil extracellular traps orchestrate formation of peritoneal adhesions

Peritoneal adhesions are a poorly understood but highly prevalent condition that can lead to intestinal obstruction, pelvic pain, and infertility. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the process of their formation remained elusive to date. Herein, we show that neutrophil extracellular traps (NETs) serve as essential scaffold for adhesion formation and that DNases interfere with this process. Thus, peritoneal adhesions in murine models and in humans showed that these lesions are largely based on extracellular DNA derived from neutrophils. Furthermore, treatment with DNASE1 or a DNASE1L3 analog significantly reduced or even prevented peritoneal adhesions in experimental models. These data not only suggest that NET formation plays an essential role in peritoneal adhesions but also show that therapeutic application of DNases can prevent the formation of peritoneal adhesions.