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.

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.

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.

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.

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.

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.