Pharmaceutical interventions play a vital role in managing various conditions, including weight-related issues such as obesity. In this context, lifestyle changes are often challenging to maintain, especially for individuals struggling with this condition. Obesity is strongly linked to serious health conditions like cardiovascular disease and insulin resistance, leading to a cascade of health risks. Importantly, the development of effective and safe weight loss medications has been challenging. Diabetes mellitus (DM), the incidence of which is also rising, is closely related to obesity. The annual rate of DM cases has increased significantly, mirroring trends in obesity. Pharmaceutical companies have made significant progress in developing drugs that address both diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising class of medications with dual benefits in managing diabetes and aiding weight loss such as semaglutide, liraglutide, dulaglutide, exenatide, among others. However, despite their effectiveness, they can be expensive. The availability of various GLP-1RAs offers flexibility in diabetes management, but the surge in their prescription has led to a global shortage. Health authorities are working to address this issue, while pharmaceutical companies are exploring new paths to improve the quality of these drugs. In this context, tirzepatide stands out as a medication targeting key hormones involved in obesity and DM. Another potential breakthrough, retatrutide, is also being developed for these two conditions, but it requires further research. In this paper, the authors address all the GLP-1RA options developed to date, covering their mechanisms of action, efficacy, and chemical structures, among other aspects.

Cyclophane-containing peptides comprise an important group of macrocyclic peptides with unique structural properties and pharmaceutical relevance. Darobactin A is a ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotic, which features an unusual biscyclophane moiety formed via the class-defining ether crosslink in addition to a carbon-carbon (C-C) crosslink. Because darobactin-like peptides (daropeptides) are widespread in nature, further exploration of these emerging RiPP natural products featuring ether crosslinked cyclophane could facilitate the discovery and development of new bioactive peptides. This perspective provides updated insights into the biosynthesis and classification of daropeptides, highlighting the potential to manipulate daropeptide maturases to access novel bioactive peptide cyclophanes.

Phytochemicals, the bioactive compounds derived from plants, play a significant role in modulating pathways leading to cancer and inflammation, rendering themselves promising candidates for therapeutic interventions. This review explores the multifaceted potential of various phytochemicals in modulating key mechanisms involved in the development and progression of cancer and inflammation. The diverse array of phytochemicals discussed here encompasses polyphenols, flavonoids, alkaloids, terpenoids, and many others, each with distinct molecular targets and modes of action. This review is an attempt to elucidate and correlate the regulatory role of phytochemicals on cellular signaling pathways implicated in oncogenesis and inflammatory responses, highlighting the significance and potential of phytochemical-based therapies for cancer prevention and treatment, as well as for managing inflammatory conditions. By exploring the promising potential of phytochemical-based remedies for cancer prevention, treatment, and inflammatory conditions and emphasizing their diverse roles in modulating critical regulatory mechanisms, this review addresses the current research landscape, challenges, and future directions in utilizing phytochemicals as effective agents against cancer and inflammation.

The FDA’s approval of resmetirom (Rezdiffra) marks a significant breakthrough in treating metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, conditions linked to non-alcoholic fatty liver disease (NAFLD). MASH is a growing global health concern, and resmetirom offers a novel therapeutic option by targeting liver pathophysiology through thyroid hormone receptor-beta activation. This mechanism effectively reduces fibrosis markers, improves liver enzyme levels, and minimizes liver fat buildup. Clinical trials have shown that resmetirom has a favorable safety profile, with manageable side effects like diarrhea and nausea. Additionally, it may lower cardiovascular risks associated with MASH, enhancing patient outcomes and quality of life. As the first FDA-approved drug for MASH, resmetirom’s introduction fills a crucial treatment gap, providing new hope for millions of patients and representing a pivotal moment in hepatology.

Sirtuins are a family of NAD⁺-dependent class III histone deacetylases that regulate histones and other proteins. The mammalian sirtuins comprise seven members that have a role in energy metabolism, DNA repair, inflammation, cell survival, apoptosis, cellular senescence, oxidative stress, and mitochondrial production. Sirtuin modulation may have beneficial effects on aging and age-related diseases; thus, attracting a growing interest in discovering small molecules modifying their activity. A class of compounds both natural and chemically synthesized has emerged as sirtuin activators. This review discusses mammalian sirtuins in aging, the small molecules that activate sirtuins, modulation of sirtuin activity, and its impact in alleviating the effects of aging.

The excessive use of antibiotics to treat bacterial infectious diseases in all living beings has caused a global epidemic of bacterial resistance to antibiotics, leading to the emergence of multidrug-resistant and pandrug-resistant strains. In 2019, the World Health Organization (WHO) reported that antimicrobial resistance causes at least 700,000 deaths per year worldwide. Therefore, in this global war against microorganisms, a therapeutic alternative is necessary to help us win this battle. A key in this race against the clock could be lactoferrin (Lf), a cationic glycoprotein of the mammalian innate immune system that is highly conserved among mammals. Lf is a multifunctional glycoprotein with immunomodulatory, anticarcinogenic, wound-healing, antioxidant, antimicrobial, and bone regeneration properties, in addition to improving the gut microbiota. Lf limits the growth of microorganisms through the sequestration of iron but can also interact directly with some components of the outer membrane of Gram-negative bacteria or bind to teichoic acids in Gram-positive bacteria, destabilizing the membrane and resulting in lysis. Moreover, cleavage of the Lf molecule could promote the production of lactoferricins (Lfcins) and lactoferrampin (Lfampin) from the N-terminal end, which are known to often have stronger antimicrobial effects than the native molecule, as well as analogous peptides, such as HLopt2, which have also shown enhanced antimicrobial activity. Bovine Lf (bLf) has been approved by the US Food and Drug Administration (FDA), and the European Food Safety Authority for its use as a dietary supplement in food products. Because of its effectiveness, accessibility, low cost, and nontoxicity, Lf could be a promising alternative for preventing or treating infections in animals and humans.

Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.

Traditional medicines and their active ingredients and some natural products and derived analogs have been used for treating multiple diseases including cancer. Among these compounds cytotoxic agents such as bleomycin, paclitaxel and vincristine block essential pathways and genes required for cancer cell growth and these agents have diverse clinical applications. Dietary phenolics including flavonoids and related compounds are associated with multiple health benefits however most individual dietary compounds and other natural products that show promising anticancer activity in preclinical studies exhibit minimal clinical effectiveness and this is particularly true for cancer. Many of the compounds perform poorly in clinical trials due to pharmacokinetic consideration and limited uptake (e.g., curcumin) and these are issues that can be addressed. The clinical effectiveness of flavonoids and many other natural product-derived anticancer compounds can also be enhanced by a more targeted approach. This would include identifying a significant response/gene or target in a specific cancer and then identifying the optimal compound. In this review, I have discussed a limited number of targets including non-oncogene addiction genes such as Sp transcription factors, reactive oxygen species (ROS) or the orphan nuclear receptor 4A (NR4A) sub-family. Thus, the most active compound for these responses could be used only for treating patients that are ROS-inducible or highly express targets such as Sp1 or NR4A sub-family members. A mechanism-based precision medicine approach should enhance the clinical efficacy of dietary and related natural products as anticancer agents and decrease toxic side effects for some combination therapies.

Biochemist Svetlana Mojsov, both as a graduate student at The Rockefeller University under the mentorship of Bruce Merrifield during the 1970s, and as an independent investigator at the Massachusetts General Hospital (MGH) during the 1980s, devised effective and robust methods for the chemical synthesis of the peptide hormones glucagon and glucagon-like peptide (GLP-1), along with numerous analogues of these key biomolecules. Working separately from MGH’s powerhouse endocrine research laboratory, Mojsov developed a tool-kit of reliable assays that were indispensable to later in vitro and in vivo collaborative studies that established profound insulinotropic effects of this peptide family, findings that were subsequently harnessed clinically with blockbuster drugs directed at often-serious endocrine conditions such as type 2 diabetes and obesity. Significantly, Mojsov was the first to recognize the critical cleavage sites in preproglucagon that give rise to the biologically active species, a truncated form known as GLP-1 (7–37), and carried out the key experiments that proved her hypothesis. Despite being the first author on critical formative publications for the field, and being acknowledged, along with Joel Habener, as one of two co-inventors on the controlling United States patents, Mojsov’s foundational contributions were initially overlooked when GLP-1 biochemistry began to be the subject of major scientific prizes. Fortunately, Mojsov’s work has, within the past year, been better appreciated and deservedly lauded.

According to the International Union of Pure and Applied Chemistry (IUPAC), peptides are small proteins with a size between 2 and 50 amino acids residues. They are ubiquitous across the evolutionary scale, fulfilling a wide variety of functions, from immune system effectors in simple organisms to signaling or neuromodulating agents in high vertebrates. Following nature’s example, peptides have emerged as alternatives in various fields. One particularly relevant area is in drug discovery, offering alternatives to face the emergence of antibiotic-resistant microorganisms. Peptides are also prevalent in other sectors, such as the food industry, where they serve as food additives to enhance nutritional characteristics or aid in food preservation. Moreover, peptides are increasingly being utilized in cosmetics. Additionally, peptides serve as valuable tools in both basic and applied research, facilitating the exploration of specific activity mechanisms and the verification of particular activities, among various other applications. Despite certain limitations and disadvantages compared to other bioactive molecules, peptides remain a focal point of interest in research, as well as in applied and developmental fields, due to their versatility. In this report, we provide an overview of the extensive application landscape of synthetic peptides, presenting examples developed in-house across different areas which include a summary of the methodologies and results obtained.

Traditional medicine systems worldwide utilize natural products (NPs), including plant-derived compounds, minerals, and organisms, harnessing their healing potential. NPs offer a rich source of potential drug candidates, driving innovation in drug discovery. Recent breakthroughs have reignited interest in harnessing the therapeutic benefits of natural compounds. Clinical applications of NP-based immunotherapies, such as curcumin and resveratrol in cancer treatment, highlight their diverse pharmacological properties. However, despite these advancements, challenges persist in the clinical implementation of NPs. Issues such as standardization, regulatory approval, and supply sustainability remain significant hurdles. Overcoming these limitations requires a concerted effort to address the complexities of NP drug development. Nevertheless, ongoing research efforts and interdisciplinary collaboration hold promise for advancing NP-based therapeutics, paving the way for the development of innovative treatments for various diseases. In the world of precision medicine, a new chapter unfolds as NPs join the therapeutic journey. The exploration of NPs as sources of bioactive compounds has revealed promising prospects for precision therapeutics in medicine. This article explores the therapeutic potential of NPs within the context of precision medicine. It examines the intricate pathways through which bioactive compounds derived from nature offer tailored therapeutic prospects, emphasizing their role in precision medicine interventions. Exploring the synergy between NPs and precision therapeutics at a molecular level, this article delineates the exciting prospect of customized treatments, signifying a transformative impact on modern medical care. The review article further highlights their potential in tailoring treatments based on individual genetic makeup and disease characteristics. Additionally, it discusses challenges and prospects, addressing issues of sourcing, standardization, scalability, and regulatory considerations to realize the full therapeutic potential of NPs.

The search for novel therapeutic agents to combat the crisis of antimicrobial resistance has spanned from terrestrial to unique, marine environments. Currently, most of the drugs available for usage are derived from microbial metabolites, especially those belonging to the bacterial group, actinobacteria. Actinobacteria are hotspot organisms that exist in all habitats with a myriad of unique biosynthetic metabolites. Seagrasses appear to be a key ecosystem within the coastal environment worth bioprospecting for novel natural products. Unfortunately, literature about the bioactive potential of their associated prokaryotes, including actinobacteria remains limited. In this context, this review focused on actinobacteria with antibiotic-producing capabilities derived from different parts of seagrass plants (i.e. roots, rhizomes, and leaves). To date, there were no purified molecules derived from seagrass-associated actinobacteria that were subjected to structure elucidation. From the underpinning of numerous biological profiles such as antibacterial, antifungal, and algicidal activities of seagrass-derived actinobacteria reported in this review during the period from 2012–2020, it provides a continual growth of knowledge accruing overtime, providing a foundation for future research.

Coronavirus disease-2019 (COVID-19) has emerged as an aggressive viral infection in the last few years. Initially reported in the Wuhan area of the People’s Republic of China, it soon emerged across the globe. Researchers confront a worrying situation to rapidly develop effective strategies to combat this novel infection and its long-term aftereffects. To date, there have been myriad reports ranging from the repurposing of the classical antimalarial drug hydroxychloroquine to several other antiviral and anti-bacterial agents like remdesivir, favipiravir, and most recently azithromycin, which has entered clinical use in many countries for combating COVID-19 infections. Several studies have highlighted the nexus between COVID-19-associated morbidity and diabetes in a wide-ranging class of subjects ranging from pediatric cases to adults and patients with other co-morbidities. Metformin is a mainstay in the treatment of type 2 diabetes (T2D). It is safe, inexpensive, and effective and does more than merely control blood sugar levels. Important metabolites that encourage blood clotting and inflammation are also suppressed by metformin. Pro-inflammatory molecules are linked to obesity and T2D. Both are major risk factors for aggravated COVID-19. These characteristics gave rise to a hypothesis that metformin may find use as an efficacious treatment for COVID-19 especially if it decreases the inflammatory molecules that fuel the COVID-19 virus-induced effects. In this review, we attempt to elucidate the role of classical anti-diabetic medicine metformin in the treatment of COVID-19 infections by highlighting the pharmacological role of this drug during elevated glucose levels and insulin resistance. We examine how COVID-19 has correlations to diabetic physiology and thereby the possibility of repurposing metformin for COVID-19 treatment.

Throughout history, biopharmaceuticals have been essential in addressing health crises and enhancing human well-being. With advancements in genetic engineering, biotechnology, and bioinformatics, the development and approval rates of new biopharmaceuticals have surged, placing them at the forefront of the pharmaceutical field. Modern manufacturing processes and streamlined regulatory pathways have further expedited approval timelines, providing hope for previously untreatable conditions and significantly improving patients’ quality of life worldwide. However, despite these advancements, ambiguity persists regarding the definition of biopharmaceuticals due to the use of varied terms and a lack of standardized definitions. This article addresses this confusion by proposing a clear and comprehensive definition of biopharmaceuticals. Additionally, we present a reclassification of biopharmaceuticals into seven distinct verticals based on their functions. We assert that biopharmaceuticals not only offer superior therapeutic benefits for human health but also contribute to environmental sustainability, promoting a healthier planet. Thus, this article aims to clarify the scope of biopharmaceuticals and advocate for their broader adoption in the pursuit of global health and environmental integrity.

With the surge of antibiotic resistance in bacteria, the need for a larger arsenal of effective antibiotics and vaccines has drastically increased in the past decades. Antibiotics like vaccines can benefit from significant potentiation when used in combination with adjuvants. Antibiotic adjuvants can allow for gram-positive bacteria (GPB) specific treatments to be used against gram-negative bacteria (GNB) infections, with minimal antimicrobial resistance (AMR). In the case of vaccines, they allow for modulation and increase of the immune response. Lipopeptides are molecules of choice because of their ability to activate specific cell surface receptors, penetrate the outer membrane of GNB, safety and ease of synthesis. This review explores the recent developments in lipopeptide adjuvants for antibiotics and vaccines, providing a roadmap on how to develop adjuvants to efficiently combat AMR. After a brief overview of bacterial resistance, lipopeptide adjuvants for antibiotics and vaccines are discussed, providing insights into stability, sources, and delivery methods. Findings discussed in this review could be applied to the development of safer, more effective adjuvants, that could expand the use or repurpose current antibiotics or improve vaccination results in future clinical trials.

With the continuous development of nanomaterials, nanofibers prepared by electrospinning have gradually occupied people’s vision because of their unique advantages, such as crisscross network and extracellular matrix-mimicking structure, high drug loading efficiency, and sustained release kinetics. Traditionally, electrospun fibers are mainly used as filter materials, wound dressings, and tissue engineering scaffolds, while their wide applications are limited to cancer nanomedicine applications due to their dense network structure. In recent years, two-dimensional fiber membranes have been transformed into short fibers that can be reconstructed to form fibrous rings or microspheres for cancer theranostics. Herein, this paper provides an overview of the recent advances in the design of electrospun short fibers that retain the advantages of nanofibers with good dispersibility for different nanomedicine applications, including cancer cell capture, cancer treatments, and cancer theranostics. The rational preparation of electrospun short fibers that are available to boost the development of nanomedicine is also discussed.