Over the last 60 years, only four new classes of antibiotics have been introduced, while the prevalence of antibiotic-resistant Gram-positive and Gram-negative bacteria has risen. This underscores the urgent need for new antibacterial therapeutics. This commentary leverages the recent exploration of γ-substituted-N-acylated-N-aminoethyl amino acid peptides (γ-AApeptides) to mimic the structures and function of natural antimicrobial peptides (AMPs), highlighting the promise and limitations for developing a new, effective treatment for antibiotic-resistant bacteria.

Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse and misuse of antibiotics in medical and agricultural settings. As bacteria adapt to evade current drugs, managing bacterial infections has become increasingly challenging, leading to prolonged illnesses, higher healthcare costs, and increased mortality. This review explores the critical role of antibiotics in fighting infections and the mechanisms that enable bacteria to resist them. Key antibiotics discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, and zoliflodacin, each with unique actions against bacterial pathogens. Bacteria have evolved complex resistance strategies, such as enzyme production to neutralize drugs, modifying drug targets, and using efflux pumps to remove antibiotics, significantly reducing drug efficacy. Additionally, the review examines the challenges in antibiotic development, including a declining discovery rate of novel drugs due to high costs and regulatory complexities. Innovative approaches, such as structure-based drug design, combination therapies, and new delivery systems, are highlighted for their potential to create compounds with enhanced action against resistant strains. This review provides valuable insights for researchers and developers aiming to combat antibiotic resistance and advance the development of robust antibacterial therapies for future health security.

Lutein, a natural dihydroxy carotenoid and a member of the non-vitamin A carotenoids family, is abundant in yellow-colored fruits and green leafy vegetables such as spinach and lettuce. As the second most common type of carotenoid found in human serum, lutein offers a plethora of medicinal benefits, including anti-cancer, anti-inflammatory, and anti-oxidative properties. It is well-absorbed and systemically localized to the liver, lung, and retina, where it can cross the blood-retina barrier and accumulate in the macular pigment. Due to its anti-oxidative and singlet oxygen quenching properties, lutein is reported to reduce the risk of age-related macular degeneration (AMD). Higher concentrations of fasting plasma carotenoids and enhanced skin yellowing after lutein consumption indicate its presence in various regions of the human body, including the skin, breast, brain, and cervix. Lutein has remarkable benefits for neurodegenerative diseases, cardiovascular health, liver protection, and bone disease prevention. In the central nervous system (CNS), lutein supports brain homeostasis through its antioxidant and anti-inflammatory properties, increasing interleukin-10 (IL-10) and reducing tumor necrosis factor-α (TNF-α). It reduces the risk of coronary artery disease and exerts anti-inflammatory effects on peripheral blood mononuclear cells (PBMCs). Lutein protects against alcohol-induced liver damage by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Additionally, lutein promotes bone health by enhancing mineralized bone nodule development and inhibiting osteoclast production, reducing bone resorption, and suppressing soluble receptor activator of nuclear factor kappa B ligand (RANKL). These multifaceted benefits make lutein a valuable agent in disease prevention and health promotion. This review discusses the comprehensive profile of lutein as a phytochemical activity, including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neurological, and cardioprotective effects. Additionally, it discusses lutein’s beneficial impact on macular degeneration and eye diseases, showcasing its potential as a natural, plant-based therapeutic agent.

Microbial biotransformations are valuable tools from “green chemistry” and involve converting parental molecules into new daughter ones with unique physical, chemical, or pharmacological properties. These reactions are often carried out by cells grown under a planktonic phenotype. However, microbial cells grown under a phenotype of biofilm can improve biotransformation bioprocesses once they form more biomass per volume, are more resistant to extreme conditions (pH, temperature, and toxic substances), remain active for extended periods, are less prone to cell washouts, and reduce re-inoculation demands, leading to increased production rates due to their unique physiological features. In addition, experience has shown that biofilms may furnish a broader array of new daughter molecules. This review highlighted the benefits of using biofilms in microbial biotransformations to obtain a variety of bioactives.

The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems.

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.

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.

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.

Traumatic brain injury (TBI) is a complex disease that leads to significant mortality and disability worldwide each year. TBI disrupts the normal activity of kinases and molecular signaling pathways, but the effective therapeutic methods for patients remain limited. Nowadays, kinase inhibitors approved by the Food and Drug Administration (FDA) mainly for cancer treatment have shown potential effects in TBI. Preclinical studies suggest their potential in promoting recovery. There are fewer randomized clinical studies that evaluate efficacy. We search the kinase inhibitors approved by the FDA and traumatic brain injury as keywords on websites and analyze associated research. This review explores the therapeutic efficacy of kinase inhibitors, identifies limitations that must be addressed in future research to advance the application of FDA-approved kinase inhibitors, and emphasizes their promising potential.

In recent years, research efforts have increased to develop new therapeutics aimed at combating antibiotic-resistant bacterial infections. These efforts focus on inhibiting the virulence factors bacteria secrete to proliferate. This review aims to highlight the advances in these antivirulence therapies, with a particular emphasis on those utilizing peptides to inhibit toxin activity. Specifically, we will review the mechanism of action of a group of toxins known as Repeat in ToXins (RTX) and the progress made regarding the use of peptides to inhibit their action. Notably, we will discuss the use of peptides mimicking either cholesterol recognition/interaction amino acid consensus (CRAC) or CARC motifs, which are similar to CRAC motifs but have the opposite orientation, to reduce their interaction with cholesterol in target cells. We will present results corresponding to the inhibition of three characteristic toxins of this group: HlyA from Escherichia coli, LtxA from Aggregatibacter actinomycetemcomitans, and CyaA from Bordetella pertussis. While these advances are very recent, they are promising for the development of new therapies. The advantage of this type of therapy is that it reduces the selective pressure for the growth of resistant bacteria.

A very new and highly specialized category of radiotracers that is still growing is radiolabeled peptides. Radiolabeled peptides, or radiopeptides, are powerful elements for diagnostic imaging and radionuclide therapy. These laboratory-manufactured peptides have gained attention due to their unique properties. The tiny structure of these peptides compared to proteins and antibodies makes them favorable regarding their availability through simple synthesis from amino acids, easy uptake by receptors on cancer cells, and high specificity and affinity for high-quality and accurate radio imaging. This study highlighted the potential of technetium-99m-labeled peptides in advancing diagnostic capabilities in directed research in Latin America.

Apoptosis is a crucial process to maintain the correct balance between healthy cells and committed-to-death cells in every tissue. The internal (or mitochondrial) and external (or death receptor) pathways are responsible for driving a series of molecular events that lead to apoptosis by releasing pro-apoptotic proteins, such as B-cell lymphoma-2 (BCL-2) homology 3 (BH3)-only proteins and second mitochondria-derived activator of caspases/diablo inhibitor of apoptosis protein-binding mitochondrial protein (SMAC/DIABLO), that in turn activate the caspase family of proteases. By counterbalancing the apoptogenic machinery, anti-apoptotic BCL-2 family members turn off pro-apoptotic signalling, favouring cell survival, a circumstance that is particularly pronounced in tumour cells in which apoptosis is deranged. Therefore, targeting the defective apoptotic process has become a viable therapeutic option for the treatment of several cancers and much effort is being made in the research and development of effective compounds. This review discussed and updated the most promising therapeutic strategies that target deranged apoptosis process in cancer by mimicking the pro-apoptotic effects of BH3-only and SMAC/DIABLO proteins.

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 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.

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.

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.