Current Pharmaceutical Design - Volume 28, Issue 1, 2022

Variants in the ryanodine receptor-1 gene (RYR1) have been associated with a wide range of neuromuscular conditions, including various congenital myopathies and malignant hyperthermia (MH). More recently, a number of RYR1 variants, mostly MH-associated, have been demonstrated to contribute to rhabdomyolysis events not directly related to anesthesia in otherwise healthy individuals. This review focuses on RYR1-related rhabdomyolysis in the context of several clinical presentations (i.e., exertional rhabdomyolysis, exertional heat illnesses and MH), and conditions involving a similar hypermetabolic state, in which RYR1 variants may be present (i.e., neuroleptic malignant syndrome and serotonin syndrome). The variety of triggers that can evoke rhabdomyolysis, on their own or in combination, as well as the number of potentially associated complications, illustrates that this is a condition relevant to several medical disciplines. External triggers include but are not limited to strenuous physical exercise, especially if unaccustomed or performed under challenging environmental conditions (e.g., high ambient temperature or humidity), alcohol/illicit drugs, prescription medication (in particular statins, other anti-lipid agents, antipsychotics and antidepressants) infection, or heat. Amongst all patients presenting with rhabdomyolysis, genetic susceptibility is present in a proportion, with RYR1 being one of the most common genetic causes. Clinical clues for a genetic susceptibility include recurrent rhabdomyolysis, creatine kinase (CK) levels above 50 times the upper limit of normal, hyperCKemia lasting for 8 weeks or longer, drug/medication doses insufficient to explain the rhabdomyolysis event, and positive family history. For the treatment or prevention of RYR1-related rhabdomyolysis, the RYR1 antagonist dantrolene can be administered, both in the acute phase or prophylactically in patients with a history of muscle cramps and/or recurrent rhabdomyolysis events. Aside from dantrolene, several other drugs are being investigated for their potential therapeutic use in RYR1-related disorders. These findings offer further therapeutic perspectives for humans, suggesting an important area for future research.

RyR1-related myopathies are a family of genetic neuromuscular diseases due to mutations in the RYR1 gene. No treatment exists for any of these myopathies today, which could change in the coming years with the growing number of studies dedicated to the pre-clinical assessment of various approaches, from pharmacological to gene therapy strategies, using the numerous models developed up to now. In addition, the first clinical trials for these rare diseases have just been completed or are being launched. We review the most recent results obtained for the treatment of RyR1-related myopathies, and, in view of the progress in therapeutic development for other myopathies, we discuss the possible future therapeutic perspectives for RyR1-related myopathies.

The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole, cyantraniliprole, etc., targets insect RyRs and can be used to control a wide range of destructive agricultural pests. The diamide insecticides are highly selective against lepidopteran and coleopteran pests with relatively low toxicity for non-target species, such as mammals, fishes, and beneficial insects. However, recently mutations identified on insect RyRs have emerged and caused resistance in several major agricultural pests throughout different continents. This review paper summarizes the recent findings on the structure and function of insect RyRs as insecticide targets. Specifically, we examine the structures of RyRs from target and non-target species, which reveals the molecular basis for insecticide action and selectivity. We also examine the structural and functional changes of RyR caused by the resistance mutations. Finally, we examine the progress in RyR structure-based insecticide design and discuss how this might help the development of a new generation of green insecticides.

Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. They can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies have indicated that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. This information may provide a novel and promising therapeutic target for autoimmune diseases.

Background: In recent decades, the prevalence of asthma has substantially increased worldwide. Advances in phytochemistry and phytopharmacology have clarified the active ingredients and biological activities of medicinal plant products for treating asthma, and the role of herbal therapies in asthma treatment has become increasingly evident. However, most plant extracts have low solubility and poor stability of bioactive components, resulting in low bioavailability and loss of efficacy. Owing to these shortcomings, the clinical use of many herbal extracts is limited. Objective: To summarise and analyse the characteristics of herbal nanoformulations and their application in asthma treatment. The objective of this review article is to address the emerging trends of herbal nanoformulations for an effective treatment of asthma. Methods: Various research and review articles from reputed international journals were referred to and compiled. Results: The nano-sized herbal formulations improve the solubility and bioavailability of herbal medicines and contribute to the sustained release of drugs, thus, increasing the therapeutic applications of herbal extracts. The review present different types of herbal nanoformulations, including micelles, nanoparticles, solid lipid nanoparticles, lipid-based liquid crystalline nanoparticles and nanoemulsions, which are potential nanodrugs for asthma treatment. Conclusions: Herbal nanoformulations have shown great prospects for the treatment of asthma in recent years. More safety and toxicity data are still needed to promote their development and application.

Candida albicans is one of the main agents responsible for opportunistic pathogenic infections. The progressive emergence of fungal resistance to conventional antibiotics and its side effects, as well as treatment costs, are considered major limitations for antifungal drugs. It has drawn scientists' attention to the search for potential substitution and reliable therapeutic alternatives for the antifungal compounds from sources like medicinal plants, which contain numerous bioactive compounds such as essential oils. Essential oils (EO), apart from having lower toxicity and better biodegradability, are eco-friendly in nature as compared with conventional antibiotics. Furthermore, extracted essential oils have been reported to possess potent antimicrobial, antiinflammatory, and antioxidant properties that nominate them as promising natural candidates to combat numerous fungal ailments. Thus, the determination of antifungal efficacy of essential oil-bearing plants on Candida spp. will provide miscellaneous knowledge for future clinical studies that are required for the development of new formulations as alternative therapeutic agents to control the growth of Candida species. Therefore, this review summarizes the gist of major essential oils that have been investigated for their anti- Candida potential with some recommendations for further study.

Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.