Current Pharmaceutical Design - Volume 29, Issue 8, 2023

Time-restricted feeding (TRF) is a special lifestyle intervention that improves glucose metabolism, regulates lipid metabolism, increases gut micro richness, and strengthens circadian rhythm. Diabetes is a remarkable component of metabolic syndrome, and individuals with diabetes can benefit from TRF. Melatonin and agomelatine can strengthen circadian rhythm, which is a crucial mechanism of TRF. New drug designs can be inspired by the related mechanisms and influences of TRF on glucose metabolism, and more researches are needed to clarify the specific diet-related mechanisms and apply this knowledge to further drug design.

Tuberculosis (TB) is a chronic, air-borne infectious disease caused by Mycobacterium tuberculosis (Mtb), which prominently affects the lungs and usually manifests in other organs. TB is preventable and curable but what makes it challenging is the emergence of resistance to the available treatment options. MDR-continued TB's expansion is one of the world's most pressing and difficult problems. Mtb revives via the reciprocity between Mycobacterium and host signalling pathways. Mtb secretes a virulence component called Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB), which helps to survive against host macrophages. It indicates that targeting secreted virulence factors offers more benefits to circumvent the emergence of resistance. Many effective inhibitors of MptpA and MptpB have been discovered, providing a solid foundation for future research and development. Aside from possessing a structurally unique binding site in the Mtb enzyme, MptpB's minimal resemblance to other human phosphatases provides a broad platform for improving selectivity over host PTPs. We believe that addressing several parts of infection processes in the host and bacteria with combination therapy is the greatest way to reduce treatment burden and medication resistance. We have discussed the recent potent, selective, and efficacious MptpB inhibitors, such as natural and marine-based, isoxazole- linked carboxylic acid-based, oxamic acid-based, and lactone-based inhibitors, as potential strategies for treating TB.

Background: For decades, mint has been used worldwide for its relieving effects against gastrointestinal disturbances. Peppermint is a perennial herb common in Europe and North America. The active ingredient of peppermint oil is menthol and has various gastroenterological and non-gastroenterological uses, especially in the context of functional gastrointestinal disorders (FGIDs). Methods: We conducted a literature search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: peppermint oil, gastro-intestinal motility, irritable bowel syndrome, functional dyspepsia, gastrointestinal sensitivity and gastrointestinal endoscopy. Results: Peppermint oil and its constituents exert smooth muscle relaxant and anti-spasmodic effects on the lower esophageal sphincter, stomach, duodenum, and large bowel. Moreover, peppermint oil can modulate visceral and central nervous system sensitivity. Taken together, these effects suggest using peppermint oil both for improved endoscopic performance and for treating functional dyspepsia and irritable bowel syndrome. Importantly, peppermint oil has an attractive safety profile compared to classical pharmacological treatments, especially in FGIDs. Conclusion: Peppermint oil is a safe herbal medicine therapy for application in gastroenterology, with promising scientific perspectives and rapidly expanding use in clinical practice.

Biomaterials have been utilised since the dawn of time to aid wound healing and to try to restore damaged tissues and organs. Many different materials are now commercially accessible for maintaining and restoring biological functioning, and many more are being researched. New biomaterials have to be developed to meet growing clinical demands. The aim of this study is to propose innovative biomaterials of human origin and their recent applications in tissue engineering and the biomedical field. Recent trends in tissue engineering are summarized in this review highlighting the use of stem cells, 3D printing techniques, and the most recent application of biomaterials to produce a dynamic scaffold resembling natural tissue. Various literature survey was carried out using PubMed, Scopus, Elsevier, google scholar, and others and it was summarized from the study that the extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Based on the literature study, biomaterials have become increasingly important to the development of tissue engineering, which aims to unlock the regeneration capacity of human tissues/organs in a state of degeneration and restore or reestablish normal biological function. Biomaterials have also become increasingly important to the success of biomedical devices. Hence, it can be concluded from the finding of the study that the advances in the understanding of biomaterials and their role in new tissue formation can open new prospects in the field of tissue engineering and regenerative medicine.

3D printing in other fields, such as aviation, is quite old, but in the pharmaceutical area, it is an emerging technique. 3D printing is used to formulate various drug delivery systems and dosage forms with complex geometry. It allows large and fast production of products according to the need of the patient. Today, it is the widely used manufacturing technique in the healthcare field for the engineering of tissues and tissue models, production of medicines and medical devices, organ and tissue bioprinting, implant manufacturing, and production of polypills, vaginal rings, orodispersible films, etc. It allows the production of various dosage forms with complex release profiles containing multiple active ingredients. It is used for manufacturing medicines according to the need of individual patients focusing on the concept of personalized medicines. The idea of customized medicines allows change of dosage and design of the product as per individual and with decreased side effects. This review details various techniques of 3D printing used, such as stereolithography, fused deposition modeling, inkjet printing, etc., and applications and dosage forms developed with the latest patents. The significant challenges in the emergence of the 3D printing technique are the involvement of complex combinations to achieve desired properties, and also, the bioprinter involved provides slow and less resolution. The materials prepared by this technique are both biocompatible and printable, due to which additive manufacturing is increasing in the field of medicine.

Background: Mitochondria are multifunctional organelles, which participate in biochemical processes. Mitochondria act as primary energy producers and biosynthetic centers of cells, which are involved in oxidative stress responses and cell signaling transduction. Among numerous potential mechanisms of mitochondrial dysfunction, the opening of the mitochondrial permeability transition pore (mPTP) is a major determinant of mitochondrial dysfunction to induce cellular damage or death. A plenty of studies have provided evidence that the abnormal opening of mPTP induces the loss of mitochondrial membrane potential, the impairment calcium homeostasis and the decrease of ATP production. Cyclophilin D (CypD), localized in the mitochondrial transition pore, is a mitochondrial chaperone that has been regarded as a prominent mediator of mPTP. Methods: This review describes the relationship between CypD, mPTP, and CypD-mPTP inhibitors through systematic investigation of recent relevant literature. Results: Here, we have highlighted that inhibiting the activity of CypD protects models of some diseases, including ischaemia/reperfusion injury (IRI), neurodegenerative disorders and so on. Knockdown studies have demonstrated that CypD possibly is mediated by its peptidyl-prolyl cis-trans isomerase activity, while the primary targets of CypD remain obscure. The target of CypD-mPTP inhibitor can alleviate mPTP opening-induced cell death. The present review is focused on the role of CypD as a prominent mediator of the mPTP, further providing insight into the physiological function of mPTP and its regulation by CypD. Conclusion: Blocking the opening of mPTP by inhibiting CypD might be a new promising approach for suppressing cell death, which will suggest novel therapeutic approaches for mitochondria-related diseases.

Background: Cancer is recognized globally as the second-most dominating and leading cause of morbidities. Breast cancer is the most often diagnosed disease in women and one of the leading causes of cancer mortality. In women, 287,850, and in males, 2710 cases were reported in 2022. Approximately 10-20% of all new cases of breast cancer diagnosed in the United States in 2017 were triple-negative breast cancers (TNBCs), which lack the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Objective: This study aims to adopt different strategies for targeting calcium integrin-binding protein 1 by computer- aided drug design methods. Our results showed that the top four selected peptides interact with CIB1 more strongly than the reference peptide and restore normal cell function by engaging CIB1. Our binding affinity analyses explore an innovative approach to planning a new peptide to inhibit triple-negative breast cancer. Methods: Molecular dynamic simulation of the CIB1-UNC10245092 interaction highlights the potential peptide inhibitors through in-silico mutagenesis and designs novel peptide inhibitors from the reference peptide (UNC10245092) through residue scan methodology. Results: The top four designed peptides (based on binding free energy) were subjected to molecular dynamics simulations using AMBER to evaluate stability. Conclusion: Our results indicate that among the top five selected peptides, the mutant 2nd mutants have more potential to inhibit CIB1 than the reference peptide (UNC10245092) and have the potency to prevent or restore the tumor suppressor function of UNC10245092.