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.

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.

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.

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.

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.

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.

Envenomation caused by snakes, scorpions, and spiders represents a serious public health problem in Latin America. The antivenoms used for its treatment are produced by immunizing horses repeatedly with sublethal doses of animal venoms along with the adjuvant. However, venom availability is a bottleneck. Furthermore, toxin-neutralizing antibodies are only a few of the total produced with this classical method. Therefore, high doses of antivenom are required to achieve the neutralization power, which usually causes adverse reactions in the patient. With the aim of obtaining a higher proportion of toxin-neutralizing antibodies while reducing the dependency on venom availability, alternative immunization protocols have been explored using synthetic peptides with epitopes from clinically relevant toxins. The process to design an immunogenic peptide entitles: (a) choice of the medical relevant toxins in the venom; (b) identification of the epitopes in the selected toxins; (c) improvement of peptide immunogenicity; (d) immunogen synthesis; and e) in vitro and in vivo evaluation. The present article aims to review the advances in the design of immunogenic synthetic peptides for their application in antivenom production in Latin America during the 21st century. Epitopes have been identified from many clinically important toxins in Latin American snakes (snake venom metalloproteinases, snake venom serine proteases, crotamine, phospholipases A2, and three-finger toxins), scorpions (beta-mammal/insect toxin Ts1, alpha-mammal toxin Ts2, alpha-mammal toxin Ts3, toxin Ts4, and beta-mammal Tt1g neurotoxin), and spiders (dermonecrotic toxin and delta-ctenitoxin-Pn2a). Nevertheless, their application is still experimental, even though they are ideal for large-scale and low-cost antivenom production, factors that are necessary to meet national and regional demands.

Migraine, a commonly occurring neurological disorder, disproportionately affects women during their reproductive years, and its symptoms are often intensified by hormonal fluctuations. This narrative review examines the impact of hormonal contraceptives, particularly combined oral contraceptives (COCs), on menstrual migraine (MM). This review assessed the impact of COCs on MM through a literature search in PubMed, Google Scholar, Web of Science, and Scopus using keywords like “menstrual migraine”, “hormone therapy”, and “COCs”. The selection criteria were peer-reviewed studies published between 2014 and 2024, written in English, and focused on MM treatment with COCs. Exclusion criteria were duplicates, editorials, irrelevant articles, and non-English studies. The literature reveals inconsistent results, with some studies reporting aggravation of migraine symptoms with COC use, whereas others indicate a decrease in the frequency and severity of attacks, especially with continuous use. Factors affecting these outcomes include patient age, menstrual cycle characteristics, and migraine type. It is crucial to choose contraceptives that suit individual patient profiles, considering the potential for increased migraine frequency or onset of migraine with aura in some women. Further studies are required to establish clear clinical guidelines. It is recommended to create personalized treatment plans that balance the effectiveness of migraine management with the overall health risks.

Cervical cancer (CaCx) is the fourth most prevalent cancer in women contributing to 341,831 annual deaths globally in 2020. Owing to its high mortality rate, the identification of novel inhibitors preventing CaCx progression is of utmost importance. Recent studies have emphasized the use of phytochemicals for cancer prevention due to their low toxicity. Psoralidin, a bioactive compound extracted from the seeds of the medicinal plant Psoralea corylifolia, showcases the potential for promoting health benefits. A range of studies showing anti-inflammatory, anti-oxidant, estrogenic, neuroprotective, anti-diabetic, anti-depressant, antimicrobial, and anti-tumor activities substantiate its promising biological effects. The anti-tumor potential of psoralidin has been well-documented. Its capacity to effectively target cancer stem cells (CSCs) in general adds to its therapeutic potential. Psoralidin carries out its anti-cancer activity by inducing oxidative stress, autophagy, and apoptosis. This unique characteristic suggests its potential to be used as an adjunct molecule in combination with existing treatment to enhance the efficacy of chemo/radiotherapy for treating CaCx. However, low bioavailability and intestinal efflux limit the use of psoralidin in clinical applications. Therefore, further investigation is needed in area of drug delivery and mechanism of action to fully harness the beneficial effects of psoralidin. The present study examines the current understanding of the molecular properties of this coumestan, as well as its various molecular targets with a particular emphasis on its anti-cancer activity. The study will help in designing effective and novel therapeutic interventions for targeting signaling pathways and other regulators involved in mediating CaCx progression, which will eventually help in effective management of CaCx.

Glioblastoma (GBM) remains a formidable challenge in neuro-oncology due to its aggressive nature and propensity for therapeutic resistance. Anti-vascular endothelial growth factor (VEGF) therapies, although promising, often encounter resistance that limits their clinical efficacy. A multi-target and multi-drug approach has emerged as compelling strategies to address this resistance to enhance the treatment outcomes. This review examines the complex environment of anti-VEGF resistant GBM and analyses a multi-target therapeutic approach using natural products.

Leishmanial diseases, caused by various species of the protozoan parasite Leishmania, continue to pose a significant global health challenge. Medicinal drugs have been at the forefront of combating these diseases, offering hope for afflicted populations. This review article provides: (1) a comprehensive analysis of current knowledge and the evolving landscape of heterocyclic drug therapies for leishmanial diseases; (2) focusing on the mechanism of drug action; (3) therapeutic effects; (4) side effects; (5) potential future directions. The review begins by outlining the critical importance of heterocyclic drugs in treating leishmanial diseases. It highlights the diverse array of drugs used to combat Leishmania and elucidates the unique mechanisms underlying their efficacy. These mechanisms include disruption of cellular processes within the parasite, interference with DNA replication, and modulation of host immune responses. In addition, the article delves into the effects and side effects of drug therapy, providing an in-depth analysis of their impact on patients. It emphasizes the need for a fine balance between effective parasite clearance and minimizing adverse effects, stressing the importance of continuous research to refine drug regimens and reduce drug resistance. The review also explores various therapies for leishmanial diseases, from chemotherapy to immunotherapy, and discusses their advantages and limitations. Furthermore, it discusses ongoing research efforts aimed at developing novel drug formulations, such as liposomal and nano-carrier-based delivery systems, to enhance drug efficacy and reduce toxicity. This article crucially focuses on future perspectives in heterocyclic drug therapies for leishmanial diseases. It emphasizes the importance of interdisciplinary research and integrating emerging technologies, such as genomics and proteomics, to identify new drug targets and strategies for disease control. The potential for combination therapies and immunomodulators to improve treatment outcomes and combat drug resistance will also discussed.

Chemo-select modification of peptides, targeting a handful of the most reactive proteinogenic amino acids (AAs), is gradually utilized to address the medical needs of peptide drugs and biopharmaceuticals. Cysteine (Cys), one of the less abundant AAs in many biological proteins, plays a vital role in the catalysis, signal transduction, and redox regulation of gene expression. In natural AAs (α-AAs) residues, Cys exhibits high nucleophilicity and low redox-active potential, making it a primary target for site-selective conjugation. This review summarizes several representative Cys-peptide/protein conjugation strategies developed in recent years, including polar reactions, radical coupling reactions, and stapling techniques.

The presence of high-quality water is essential not only for human survival but also for the well-being of plants and animals. This research aimed to examine studies investigating the occurrence of antibiotics, endocrine disruptors, and other pharmaceutical products in water, sediments, and organisms within aquatic ecosystems. These substances have been linked to numerous adverse health effects on both humans and aquatic life, including reproductive issues and neurotoxic effects. The pervasive utilization of antibiotics in medical and agricultural domains has precipitated their ascension as formidable environmental contaminants. Effluents discharged from pharmaceutical industries constitute significant contributors to aquatic ecosystems’ contamination with antibiotics. These pharmacological agents permeate diverse environmental niches, spanning groundwater, surface water, soils, and wastewater treatment facilities, exhibiting concentrations ranging from nanograms to grams per liter. Concurrently, the indiscriminate and excessive application of antibiotics worldwide has engendered escalating apprehensions pertaining to antimicrobial resistance—a formidable global health exigency. This review also delves into the impact of pharmaceutical pollutants on aquatic environments, particularly as endocrine-disrupting compounds. Analysis of surface water in River Taff and River Ely reveals a consistent discharge of approximately 6 kilograms of pharmaceuticals per day. The study examines particular pharmaceuticals, such as diethylstilbestrol (DES), chlorotriazines, chloroquine, and antineoplastic drugs, elucidating their varied effects on reproductive cycles. Pharmaceutical pollutants in aquatic ecosystems, originating from sources like wastewater, agriculture, and improper disposal, persist and adversely affect organisms through bioaccumulation and biomagnification. These contaminants pose significant ecological and health risks, necessitating effective mitigation strategies.

Age-related pathologies, particularly cardiovascular disorders, pose a significant global health concern. The World Health Organization (WHO) predicts an increase in advanced mortality by 2030 unless critical interventions are implemented. Atherosclerosis remains the major cause of various cardiovascular diseases. Hence, this review focused on the interaction between known mechanisms of vascular aging, disease manifestation, and progression during atherosclerosis. In the review, we highlighted five altered vascular mechanisms in cardiovascular models: genomic instability, neurohormonal deregulation, epigenetics, protein regulation, and the gut microbiome. The articles were selected from various indexed scientific databases. It is important to note that the mechanisms are equally interrelated with other aging pathways, such as inflammation and senescence. In conclusion, atherosclerosis is multifaceted and cholesterol-lowering therapy has been widely used. However, more than one specific action line is required to eradicate or slow down its manifestation. Equally, establishing a balance between aging stressors resulting in vascular injuries and stress buffering mechanisms during aging is critical to the treatment of atherosclerosis. The promising therapeutic targets reviewed include the angiotensin (1–7)/MAS axis, the gut microbiome, histone deacetylases, DNA repair systems, noncoding RNAs, β3/dopamine adrenoceptors, senescence and inflammation checkpoints.

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.

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.

Premature aging can be partially explained by inefficient autophagy (the process of cellular self-digestion that recycles intracellular components) and premature senescence (cease of cellular division without cell death activation). Autophagy and senescence are among the basic biochemical pathways in plants and fungi suggesting that some of their metabolites have the potential to act as autophagy inducers (AI) and senescence inhibitors (SI) and to inhibit inflammation and human aging. Several compounds have already been identified: trehalose and resveratrol are natural compounds that act as AI; flavonoids found in fruit and vegetables (curcumin, quercetin, and fisetin) are among the first SI discovered so far. New AI/SI can be identified using various approaches like hypothesis-driven approach for screening receptor agonists using an in-silico library of thousands of natural compounds; cheminformatics studies of phytochemicals using docking and molecular dynamics simulation, structure similarities/mimicry in vitro, “blind” high throughput screening (HTS) of libraries of natural metabolites against relevant models, and more. This article aims to promote the use of plant and fungi novel resources to identify bioactive molecules relevant for healthy aging based on the knowledge that plants and fungi use autophagy and senescence mechanisms for their own survival and homeostasis. As autophagy and senescence are interconnected, how drugs targeting autophagy, senescence, or both could contribute to healthy aging in humans will be speculated.

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.

In recent times, there has been a revolutionary surge in antioxidant research, with a focus on harnessing microalgae to enhance wellness and extend human longevity. Microalgae, a diverse group of unicellular photosynthetic organisms, have emerged as promising sources of natural antioxidants due to their ability to synthesize various bioactive compounds, including carotenoids, polyphenols, and tocopherols. These antioxidants play a pivotal role in scavenging free radicals and reducing oxidative stress, known contributors to aging and chronic diseases. This review provides an over-view of recent advancements in understanding microalgae’s antioxidant potential, covering their biochemical composition, extraction techniques, and purification methods. Moreover, it delves into compelling in vitro and in vivo studies showcasing microalgae-derived antioxidants’ protective effects against oxidative damage, inflammation, cardiovascular diseases, and neurodegenerative disorders. The sustainable cultivation of microalgae in controlled environments further supports the potential for large-scale production and commercialization of their antioxidant compounds. As microalgae continue to revolutionize antioxidant research, they hold immense promise in developing novel preventive and therapeutic strategies to promote human health and wellbeing.

The potent pain-relieving properties of opioids come at a steep price. Their addictive nature and side effects raise critical concerns in managing pain after surgical spine procedures. Postoperatively, spinal surgeries often accompany acute intense pain, which presents a significant challenge in optimal recovery. This paper reviews the historical approach to pain management in spine surgeries and expands on the use of alternatives and novel agents with reduced addictive potential. Additionally showcasing individualized multimodal strategies for postoperative pain management beyond pharmacological approaches such as cognitive behavioral therapy (CBT), physical therapy, and transcutaneous electrical nerve stimulation (TENS). Given the global opioid addiction crisis, there is a growing need for a fundamental shift towards safer and effective alternatives. Transitioning beyond opioid-centric practices in spinal surgery can optimize pain relief while improving patient outcomes and minimizing risk.

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.

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.

Protein-protein interactions (PPIs) impersonate a significant role in many biological processes and are potential therapeutic targets in numerous human diseases. Stapled peptides, as the most promising therapeutic candidate for interfering with PPIs, have a higher degree of α-helicity, improved binding affinity, more resistance to proteolytic digestion, longer serum half-life, and enhanced cell permeability, which exhibits higher pharmacological activity compared with small molecule drugs and biologics. This review outlined the continuous progress of stapled peptides mainly concerning the design principle, structural stability, bioactivity, cell permeability, and potential applications in therapeutics, which is aimed at providing a broad reference for the design and exploration of stapled peptides with enhanced biological and pharmacokinetic properties as the next-generation therapeutic peptide drugs targeting various diseases.

Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)⁺ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD⁺ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.

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.

The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment of viral particles to the host cell membrane receptor and membrane fusion. Due to its crucial involvement in the initial phases of influenza A infections, HA emerges as a promising target in the search of novel drug-like candidates. Given its pivotal role in the early stages of influenza A infections, intense drug discovery efforts have been undertaken to target HA in the past decades. Drug discovery studies mainly rely on preventing the recognition of sialic acid units by the receptor binding site in the globular head (GH) domain, or the conformational rearrangement required for the fusion of viral and cell membranes. In this work, the aim is to summarize the progress made in HA-targeted development of small molecule fusion inhibitors. To this end, attention will primarily be focused on the analysis of the X-ray crystallographic structures of HA bound to fusion inhibitors. Furthermore, this study also aims to highlight the efforts made in exploiting the structural information in conjunction with molecular modeling techniques to discern the mechanism of action of the fusion inhibitors and to assist the design and interpretation of structure-activity relationships of novel lead compounds will be highlighted. The final section will be dedicated to elucidating novel and promising antiviral strategies proceeding from the transformation of known small molecule antivirals in proteolysis targeting chimera (PROTAC)-based targeted protein degradation. This knowledge will be valuable to assist the exploitation of classical and novel antiviral structure-based strategies, together with a deeper understanding of the mechanism of action and minimization of the impact of drug resistance.

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.

The environmental impact of drug manufacturing raises concerns about sustainability in healthcare. To address this, exploring alternative approaches to drug production is crucial. This review focuses on seaweed as a sustainable resource for greening drug manufacturing processes. Seaweed offers advantages such as renewability, abundance, and a positive environmental footprint. The review begins by providing an overview of sustainable drug manufacturing practices and the challenges faced in achieving sustainability. It then discusses seaweed as a sustainable resource, including cultivation techniques and environmental benefits. Seaweed has various applications in drug manufacturing, including extracting and purifying bioactive compounds with potential therapeutic properties. Seaweed’s role in developing green technologies, such as seaweed-based excipients, biodegradable packaging materials, and as a source of sustainable energy for drug manufacturing processes, is highlighted. The environmental and economic implications of incorporating seaweed-based solutions are discussed, emphasizing reduced carbon footprint and cost-effectiveness. Regulatory and industrial perspectives are addressed, examining challenges, and opportunities for implementing seaweed-based drug manufacturing. Collaboration between academia, industry, and regulatory bodies is crucial for successful integration. The review presents future directions and opportunities, including emerging trends and innovations in seaweed-based drug manufacturing, areas for further research, policy development, and industry engagement recommendations. Incorporating seaweed into drug production facilitates a reduction in environmental impact, promotes resource efficiency, and contributes to sustainable healthcare. This review showcases seaweed-based solutions as a means to foster a greener future for drug manufacturing, addressing environmental concerns, and promoting sustainability.

3₁₀-Helices represent the third most abundant secondary structure proteins. Although understandably overshadowed by α-helices for decades, the 3₁₀-helix structure is slowly regaining certain relevance in protein science. The key role of this secondary structure in biological processes has been highlighted in reports over the last decade. In addition, 3₁₀-helices are considered key intermediates in protein folding as well as a crucial structure for the antimicrobial activity of naturally occurring peptaibols. Thus, it is clear that 3₁₀-helices are relevant scaffolds to take into consideration in the field of biomimetics. In this context, this review covers the strategies developed to stabilize the 3₁₀-helix structure in peptide chains, from the incorporation of constrained amino acids to stapling methodologies. In the last section, the use of 3₁₀-helices as scaffolds of interest in the development of bioactive compounds, catalysts for enantioselective reactions, supramolecular receptors, and membrane-embedded signal transducers are discussed. The present work aims to highlight the relevance, sometimes underestimated, of 3₁₀-helices in chemical biology and protein science, providing the tools to develop functional biomimetics with a wide range of potential applications.

Nucleic acid therapeutics are emerging as a promising class of medicines, offering unique therapeutic options for cancer at the gene level. However, the druggability of nucleic acid therapeutics is fundamentally restricted by their low stability, poor membrane permeability, and low bioavailability, necessitating the use of delivery vectors. Various delivery vectors have been developed for nucleic acid therapeutics. The fate of established nucleic acid delivery systems (NADS) in vivo substantially affects the delivery efficiency and therapeutic efficacy. The physicochemical properties of NADS (such as size, charge, shape, etc) are crucial for the interaction of NADS with various biological barriers in the body, thereby determining the fate of NADS in the body. Nanoparticle (NP) size is an important parameter defining the blood circulation, distribution, tumor accumulation, and cellular uptake of NADS. This mini-review briefly introduces the various biological barriers of NADS in cancer treatment and focuses on the influence of the particle size of delivery vectors on the in vivo fate of NADS and their therapeutic efficacy, which provides new insights into the rational design of NADS.

Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations.

Seaweeds, also known as marine algae, have gained attention as a promising source of bioactive compounds with potential applications in drug discovery. This review explores the emerging field of seaweed-based drug discovery and highlights the diverse range of bioactive compounds found in seaweeds, including polysaccharides, phlorotannins, pigments, and peptides. These compounds exhibit various pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, antiviral, and anticancer effects. Seaweeds have demonstrated particular promise in the areas of cancer research, with certain species showing potent antitumor properties. Additionally, their anti-inflammatory, antimicrobial, and neuroprotective potential has captured scientific interest in the treatment of chronic diseases and neurodegenerative disorders. However, challenges related to compound identification, extraction methods, scalability of seaweed cultivation, and understanding the mechanisms of action still need to be addressed. As researchers employ advanced technologies and dive deeper into the chemical composition of seaweeds, the untapped potential of these marine organisms in drug discovery awaits further exploration and holds significant promise for future therapeutic advancements.

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.

Reactivation of hepatitis B virus (HBV; RHBV) is a significant concern during immunosuppressive therapy, as it can lead to severe hepatitis and liver failure. The article reports a case of RHBV during treatment with guselkumab, an interleukin-23 inhibitor in a patient with inactive HBV infection and psoriasis. This report highlights the importance of screening for HBV prior to immunosuppressive therapy and initiating prophylactic therapy when necessary to prevent reactivation and its complications.

Protein therapeutics are extensively used in the treatment of autoimmune diseases, but a subset of patients appears to be refractory to these treatments, mainly due to the development of an immune response to the drug. A better understanding of the mechanism underlying the therapeutic drug’s failure becomes fundamental for the development of new and more effective treatments. Unfortunately, there are few cases where the exact mechanisms through which drugs bypass immunological tolerance and provoke immunogenicity have been studied. In this context, peptide epitope identification gained increasing importance in investigating the molecular mechanism of therapeutic drug’s immune responses. Despite peptide identification and use to monitor anti-drug antibody (ADA) profiles is a promising research field, their use is far away from a wide application both at the research and at the commercial level. Herein it is reported a compilation of studies in which peptides are directly involved in anti-drug immune responses, becoming the molecular key step for a better understanding of refractory reactions in therapeutic drugs. An overview on T-cell and B-cell peptide recognition is given, showing the growing potential and advantages of peptides when used in the field of refractoriness to drugs. This review includes studies describing antigenic peptides that enable enhanced ADA detection directly in patients’ sera, as well as the proof of concept that asses the use of peptides instead of proteins, to facilitate the identification of neutralizing ADA.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field.

Green propolis is collected by Apis mellifera from the flowers and buds of Baccharis dracunculifolia. It has several chemical compounds that confer anti-inflammatory, antimicrobial, healing, and antioxidant biological activities. To report a series of clinical cases in the treatment of oral mucositis (OM) in patients with cancer undergoing radiotherapy in the head and neck region. Rapid treatment of OM means restoring quality of life to patients and lowering the cost of cancer treatment for public health. There male patients with oral carcinoma undergoing radiotherapy treatment were followed between August 2018 and April 2019. The patients presented themselves to the clinics in the Faculty of Dentistry of Federal University of Minas Gerais with erythematous and ulcerated coalescing lesions with purulent fibrin pseudomembranes in the oral mucosa, classified as grade IV OM according to the World Health Organization. The patients complained about the inability to eat, drink, and speak, which caused the radiotherapy interruption. After completing the clinical forms, anamnesis, and proper oral hygiene of each patient, a mucoadherent gel containing 5% propolis was prescribed for daily use, with a 3 time-a-day application every 8 h. After 7 days of use, there was an 80% lesion reduction, with total remission after 15 days of its application. The rapid response with total remission of lesions seems to be related to the chemical composition of propolis. Clinical and cellphone monitoring of patients, weekly and daily, respectively, were essential for successful treatment. The patients were monitored for one year, being encouraged to make constant use of the gel to control hyposalivation caused by changes in the salivary glands during radiotherapy.

Flavonoids present a large group of natural polyphenols with numerous important health benefits for preventing and treating a diverse variety of pathological conditions. However, the actual therapeutic use of these phytochemicals is impeded by their low oral bioavailability. In this commentary article, an interesting paradox is presented: while the ingested flavonoid glycosides can be absorbed by means of sodium-dependent glucose transporters (SGLTs; SGLT1) located in the brush border membrane facing the lumen of the small intestine, certain flavonoid aglycones are able to inhibit these shuttle proteins. It is expected that avoiding the co-intake of such SGLT1 inhibitors concomitantly with flavonoid-rich foods might provide a new option for enhancing the oral bioavailability of flavonoids, thereby preventing the transport of unabsorbed compounds to the large intestine and conversion into catabolites by the colonic microbiota. Altogether, the administration of flavonoids in appropriate combinations is highlighted for getting the maximal health benefits from consuming these bioactive compounds.

Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 10⁹/L] correlates, with an increased risk of bleeding during the main diagnostic-therapeutic procedures which cirrhotic patients usually undergone. In these cases, generally, an infusion of platelets is performed, albeit in recent years has been replaced by a cycle of second generation thrombopoietin receptor (TpoR) agonists. This article reports two different cases concerning respectively an 83-year-old female patient suffering from arterial hypertension, aneurysm of the sub-renal aorta, hepatitis C virus (HCV)-positive liver cirrhosis responsive to treatment with antiviral drugs, and a 2.0 cm diameter hepatocellular carcinoma (HCC) nodule localized in the hepatic segment III and a 53-year-old female patient with HCV-positive liver cirrhosis complicated by portal hypertension with splenomegaly, thrombocytopenia, and F3 esophageal varices at high risk of bleeding. Both of them, eligible for invasive procedures such as HCC transarterial chemoembolization (TACE) and for esophageal variceal band ligation, were prescribed prophylaxis with TpoR agonists due to their severe and persistent thrombocytopenia. These two cases show how a short course of lusutrombopag allows to safely perform one or more invasive procedures and how the administration of the drug can be repeated without losing efficacy. Furthermore, this drug shows an excellent safety profile and avoids the risks of platelet transfusion. In conclusion, second generation TpoR agonists can be considered the prophylactic treatment of choice to reduce the risk of bleeding in patients with liver cirrhosis and severe thrombocytopenia.

Despite recent advancements in the field of neuro-ophthalmology, the rising rates of neurological and ophthalmological conditions, mismatches between supply and demand of clinicians, and an aging population underscore the urgent need to explore new therapeutic approaches within the field. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), traditionally used in the treatment of type 2 diabetes, are becoming increasingly appreciated for their diverse applications. Recently, GLP-1RAs have been approved for the treatment of obesity and recognized for their cardioprotective effects. Emerging evidence indicates some GLP-1RAs can cross the blood-brain barrier and may have neuroprotective effects. Therefore, this article aims to review the literature on the neurologic and neuro-ophthalmic role of glucagon-like peptide 1 (GLP-1). This article describes GLP-1 peptide characteristics and the mechanisms mediating its known role in increasing insulin, decreasing glucagon, delaying gastric emptying, and promoting satiety. This article identifies the sources and targets of GLP-1 in the brain and review the mechanisms which mediate its neuroprotective effects, as well as implications for Alzheimer’s disease (AD) and Parkinson’s disease (PD). Furthermore, the preclinical works which unravel the effects of GLP-1 in ocular dynamics and the preclinical literature regarding GLP-1RA use in the management of several neuro-ophthalmic conditions, including diabetic retinopathy (DR), glaucoma, and idiopathic intracranial hypertension (IIH) are discussed.

Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance, metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum stress, and hepatic fibrosis. This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infections control methods have been developed. Nevertheless, all of them have certain limitations: uncertainty in duration, limited efficacy of vaccines, and lack of effective drugs for COVID-19 treatment. So, the issue of creating drugs for symptomatic and etiotropic therapy is still relevant. This review summarizes the current knowledge of using natural compounds as anti-SARS-CoV-2 agents by analysing the results of in vitro studies and completed clinical trials (CTs). Also, this work highlighted the most active molecules and discussed the possibility of using some compounds in clinical practice.

Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the ability of bacteria to adapt and to survive. Indeed, bacteria have developed various mechanisms of resistance against several therapeutic agents. Consequently, the scientific community is always interested in search of new therapeutic agents, which are able to efficiently kill resistant-bacterial strains. This article covers the most recent antibacterial molecules approved by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) from 2012 to 2022 and intends to focus on synthetic derivatives to give a pedagogical view, with the goal of highlighting the importance of organic synthesis to obtain greater efficacy. A focus will be made on studies describing the structure and activity of the organic molecules and their interactions with their respective biological targets.

Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.

Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

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.

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.