Purpose: The main aim of this review is to investigate the potential role of alpha-lipoic acid (ALA), which is a naturally occurring antioxidant in the prevention and management of radiation-induced oral mucositis (RIOM) in head and neck cancer patients undergoing radiotherapy sessions. It highlights the antioxidant, anti-inflammatory, and radioprotective effects of ALA found in preclinical and clinical studies.Methods: A comprehensive literature search was carried out using the Egyptian Knowledge Bank, PubMed, and Google Scholar databases by applying key terms such as “alpha-lipoic acid,” “oral mucositis,” “radiotherapy,” “antioxidants,” and “head and neck cancers“ to find important preclinical and clinical studies that were published in English. Findings: Numerous preclinical and clinical studies have demonstrated that the antioxidant and anti-inflammatory effects of ALA are beneficial in various diseases. Also, ALA showed protective effects against radiation-induced oral mucosal damage in three animal studies due to ALA’s ability to improve the activity of antioxidant enzymes, suppressing the pro-inflammatory signaling pathways, and reducing apoptosis in irradiated oral tissues.Implications: The potent anti-inflammatory and antioxidant properties demonstrated in clinical trials, as well as its radioprotective effects observed in animal studies, make alpha-lipoic acid (ALA) a promising supportive treatment for the management of RIOM in head and neck cancer patients. These effects also support its potential inclusion into clinical protocols in the future. However, this can only be applicable after performing further investigations and more extensive clinical trials in order to determine the ideal dose, effectiveness, and safety in RIOM patients.
Paclitaxel is a well-known chemotherapeutic agent used to treat various cancers, including breast, lung, and pancreatic cancers. However, its effectiveness is limited by significant adverse effects, including neurotoxicity, nephrotoxicity, hepatotoxicity, testicular toxicity, and cardiotoxicity. In this review, we focused on its potential cardiotoxicity. The mechanisms underlying Paclitaxel-induced cardiotoxicity have not been thoroughly elucidated. In the current review, we highlighted the possible mechanisms involved in Paclitaxel-induced cardiotoxicity. This may include activation of oxidative stress as evident by elevation in cellular lipid peroxidation, and decrease in Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), and Catalase (CAT) activity. Moreover, oxidative stress induces cell death, as well as activation of the inflammatory response. Paclitaxel-induced inflammation was evident by the release of inflammatory cytokines and chemokines. In addition, ferroptosis, which is a form of cell death characterized by accumulation of iron, is thought to be a possible underlying mechanism of Paclitaxel-induced cardiotoxicity. Furthermore, Paclitaxel causes cardiotoxicity through stimulation of apoptotic pathways. Taking all together, Paclitaxel-induced cardiotoxicity affects the quality of life of cancer patients and is considered a challenge facing pharmaceutical research nowadays.
Drug discovery process is a complex and costly process requiring a huge investment of time and money with a high risk of failure. Recently, drug repurposing or repositioning is gaining attention and focus especially with less time needed and known safety profile for the repurposed medication. Researchers keep searching for candidate medications to be repurposed. Cilostazol is a phosphodiesterase III inhibitor used primarily in intermittent claudication. It is readily absorbed from the GIT with 95% of the medication being protein bound and is metabolized in the liver with cytochrome P450. Cilostazol has shown potential for being repurposed owing to its anti-inflammatory, antioxidant and anti-apoptotic effects, in addition to a well-known safety profile and tolerable side effects which are explored and highlighted in this review. Furthermore, this review inspects the preclinical and clinical studies that showed the therapeutic benefits of cilostazol when used as a cardioprotective, hepatoprotective, nephroprotective and neuroprotective. Overall, cilostazol may be a potential candidate medication to be used as an add-on therapy for various conditions owing to its diverse therapeutic actions.
Despite improvements in pharmacological treatments, myocardial infarction (MI) continues to be a major cause of heart failure and a global health burden. By inhibiting aldosterone-mediated pathways implicated in inflammation, oxidative stress, and cardiac fibrosis, mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, have demonstrated efficacy in the treatment of MI. The wide range of clinical responses to MRAs, however, emphasizes the necessity of precision medicine strategies. By modifying receptor sensitivity, aldosterone synthesis, and downstream signaling, genetic variations within the renin-angiotensin-aldosterone system (RAAS), specifically in genes like CYP11B2, NR3C2, ACE, AGT, and AGTR1, may have a substantial impact on MRA efficacy. With an emphasis on functional outcomes measured by echocardiographic parameters and a variety of circulating biomarkers, such as aldosterone, total antioxidant capacity (TAC), transforming growth factor-beta1 (TGF-β1), interleukin-6 (IL-6), and brain natriuretic peptide (BNP), this review examines the available data on RAAS-related genetic variations and their relationship to MRA response in MI patients. We also go over how pharmacogenomic testing may help direct customized treatment, minimize side effects, and improve long-term cardiovascular results. More focused, efficient management techniques in post-MI care may be possible with an understanding of the gene-drug interactions within the RAAS pathway.
Breast cancer (BC) is considered the leading type of cancer among women globally. Several treatment strategies are available for BC management including surgery, radiation therapy, and chemotherapy. Despite the efficiency of most systemic chemotherapeutic agents, none could achieve patients’ compliance rather than compromising their quality of life due to their severe side effects. Thus, considerable attention has been paid to exploring an efficient and localized alternative drug delivery route for BC management surpassing the obstacles of the traditional administration routes. Local transdermal therapy (LTT) is an emerging drug delivery approach under investigation for targeted BC treatment, as it could efficiently provide a localized subcutaneous drug accumulation upon topical application on breast skin rather than the systemic drug distribution. Nevertheless, the protective function of the skin could be a hurdle for the optimal drug transportation into the deep breast tissue. Thus, encapsulating drugs within suitable nanocarriers could be one of the potential strategies to defeat this limitation. Flexible nanovesicles mainly transferosomes (TFs) and high penetration vesicles (HPVs) have been investigated for enhancing anticancer drugs percutaneous delivery via LTT. Moreover, their composition, mechanism of skin penetration, different preparation methods, and characterization tests have been also discussed in detail. Therefore, harnessing of penetrable nanocarriers for targeting novel anticancer candidates employing the LTT pathway could be a promising avenue for the optimal management of BC. Furthermore, the integration of different machine learning (ML) algorithms for the selection of optimal nanocarrier systems for targeted drug delivery provides a brighter future for BC treatment.
The COVID-19 pandemic has accelerated vaccine development and deployment, with intake of over 13 billion doses globally as of 2023. While these vaccines demonstrate remarkable efficacy in reducing severe outcomes, emerging evidence suggests complex interactions between vaccination, gut microbiome composition, and long-term immune responses. This review investigates and shows the understanding of how vaccines may influence health and immune function through microbiome changes, especially for enhancing vaccine efficacy and public health outcomes. The interaction of microbial ecology and vaccine pharmacology presents novel opportunities for personalized immunization strategies but requires rigorous longitudinal studies to establish causal mechanisms. We address key challenges like vaccine distribution and safety concerns, offering recommendations for effective risk communication and collaborative research. Ultimately, the continuous evaluation of vaccine safety, microbiome interactions, and long-term effects is essential for optimizing global vaccination efforts and evidence-based decision-making. KEYWORDS COVID-19 vaccines, Microbiome-Vaccine interactions, Vaccine Pharmacovigilance, COVID-19 Immunogenicity, Gut microbiota Impact, Adverse Events following immunization (AEFI), Immunogenicity
Juvenile Idiopathic Arthritis (JIA) is one of the most prevalent rheumatologic disorders affecting children. It is characterized by progressive joint damage and chronic synovial inflammation that primarily arise from oxidative stress and immune dysregulation. While conventional therapies, including disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and corticosteroids, have improved disease outcomes, challenges such as adverse effects, high costs, and incomplete remission persist. Recently, natural antioxidant and anti-inflammatory dietary supplements exhibit potential as adjunctive therapies alongside standard treatments. This review presents current evidence on bioactive supplements, specifically coenzyme Q10, omega-3 fatty acids, and curcumin, evaluating their immunomodulatory and anti-inflammatory effects in the context of chronic autoimmune conditions, such as rheumatoid arthritis (RA) in adults and JIA in pediatrics. The shared pathophysiological features between RA and JIA, notably inflammation, cytokine overexpression, and redox imbalance, underscore the rationale for nutraceutical intervention. Drawing on mechanistic insights, preclinical and clinical studies, and meta-analyses primarily from RA literature, this article bridges critical gaps in pediatric research by extrapolating findings to the JIA population. The review features robust evidence supporting these agents’ efficacy in modulating proinflammatory cytokines, reducing oxidative biomarkers, and improving disease activity scores. Importantly, early clinical trials in JIA demonstrate promising benefits with omega-3s and curcumin, showing reductions in severity scores and inflammatory markers without added toxicity. By presenting a critical analysis of existing data and identifying key gaps, this article lays the foundation for future pediatric trials and personalized, adjunctive strategies that may enhance disease management and quality of life in pediatric patients with JIA.
Jasminum, a medicinal plant from the Oleaceae family, has been utilized for centuries. Jasminum species including Jasminum grandiflorum L., Jasminum sambac L. Aiton, Jasminum azoricum L., and Jasminum humile L. have been used traditionally for their antimicrobial, anti-cancerous, anti-ulcerative, antidepressant, anti-inflammatory, fragrance, and flavoring purposes. Besides, Jasminum species were employed to treat dermatitis, fever, conjunctivitis, breast cancer, discomfort in the abdomen, asthma, abscess, uterine hemorrhage, headache, tooth pain, sleeplessness, digestive disorders, diarrhea, and menorrhagia. Moreover, Jasmine oil has been commonly used in aromatherapy. Jasmine essential oil components work together to provide antibacterial, anti-acne, spasmolytic, and aromatherapy benefits. This study reviewed the medicinal characteristics of Jasminum species, including their anti-inflammatory, antioxidant, cytotoxic, antimicrobial, antifungal, anthelmintic, antiviral, wound healing, anti-aging, antidepressant, antihypertensive, anti-lipid peroxidative, anticonvulsant, and antifertility effects. The current review article attempts to emphasize the ethnobotanical and conventional applications. This review highlights the pharmacological activity of Jasminum species, primarily on investigations from the last ten years. Furthermore, the pharmacological properties of Jasminum species were defined.
Colistin, a polymyxin antibiotic, is an essential last-resort agent that was discovered in the late 1940s for the treatment of severe infections brought on by pan-drug-resistant (PDR), extensively drug-resistant (XDR), and multidrug-resistant (MDR) Gram-negative bacteria (GNB), particularly Enterobacteriaceae such as Klebsiella pneumoniae and E. coli, as well as Pseudomonas and Acinetobacter. Despite its efficacy and utility as a final line antibiotic, the emerging of colistin resistance has been rising. Resistance mechanisms to colistin involve chromosomal mutations that alter the colistin’s binding target, upregulation of efflux pumps, and plasmid-mediated mcr genes, which enable horizontal gene transfer and rapid dissemination among bacterial populations. This review focuses on the mode of action of colistin, with special attention to resistance mechanisms, particularly the alarming spread of mcr genes worldwide. Furthermore, it discusses phenotypic methods for detecting colistin resistance, which are vital for clinical surveillance and antibiotic stewardship programs. Understanding these resistance pathways is critical for guiding treatment strategies and controlling the spread of resistant pathogens in healthcare settings.
Heart failure is a complicated syndrome with an array of causes which is associated with reduced cardiac function and highly heterogeneous treatment responses. Recently, there has been no clinical optimization of outcomes due to the intensive reliance on pharmacological therapies which further necessitates the development of personalized treatment approaches. Strides in HF medicine came with the advent of sodium-glucose co-transporter 2 inhibitors (SGLT2Is) such as Dapagliflozin, Empagliflozin and canagliflozin which have shown to be useful in HF due to its cardioprotective property beyond controlling glucose, reducing cardiovascular mortality, and hospitalization. However, it is well documented that responses to treatment with SGLT2Is are heterogeneous and this may be due to genetic polymorphisms affecting important pathways like cardiac function, inflammation, and fibrosis among others. This review explores the effects of SGLT2 inhibitors on cardiac remodeling in heart failure, focusing on left ventricular ejection fraction (LVEF), echocardiographic changes, and fibrosis biomarkers. The review will also highlight the importance of genetic testing in shaping clinical decisions and the management of HF. Such an effort may shift the treatment paradigm of HF patients and significantly improve their prognosis.
Genus Sapindus (family Sapindaceae), widely known for its saponin-rich soapberries, has long held a place in traditional medicine across Asia and the Americas. This review provides a comprehensive overview of the phytochemical profiles and antimicrobial activities of key Sapindus species, including S. mukorossi, S. emarginatus, S. trifoliatus, and S. saponaria. Through an extensive literature review and inclusion of recent molecular docking studies, the therapeutic potential of saponins and related compounds in combating bacterial, fungal, and viral pathogens, including antibiotic-resistant strains was discovered. The bioactive constituents were assessed for their mechanistic interactions with microbial targets, highlighting their membrane-disruptive, enzyme-inhibitory, and antibiofilm properties. Notably, in silico docking results support the strong binding affinities of specific Sapindus-derived compounds to microbial enzymes and virulence factors, reinforcing their potential as lead candidates for natural antimicrobial development. Data were collected from utilizing multiple scientific databases including PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect. This review focused primarily on research published in the past 20 years It not only consolidates decades of ethnopharmacological and experimental data but also bridges traditional knowledge with modern computational tools to illuminate new paths for antimicrobial drug discovery.
Epilepsy diagnosis requires the occurrence of at least one seizure, while status epilepticus (SE) is a life-threatening condition with prolonged seizures without a return to baseline consciousness, often requiring emergency intervention. Epilepsy is a chronic neurological disorder with neurobiological, cognitive, psychological, and social complications. It is characterized by the recurrence of unprovoked seizures that last from seconds to hours per seizure. The precise pathophysiology of epilepsy remains unclear despite extensive research, and several predisposing factors contribute to its occurrence, such as head injury, stroke, genetic predispositions, or infection. Ferroptosis is an iron-mediated, regulated form of cell death driven by overload of iron, leading to accumulation of reactive oxygen species (ROS). It has been considered in recent research as a contributing mechanism to predisposing lipid peroxidation and causing implication in several neurological disorders, including epilepsy. According to recent studies, ferroptosis inhibition is probably a successful treatment strategy for epilepsy. This review article provides an insight into the ferroptosis axis and the related pathogenesis, highlighting the key regulatory elements such as peroxidase 4 (GPX4), system Xc⁻, and iron metabolism. It further explores how dysregulation of these elements may contribute to epileptogenesis and seizure propagation, with the aim of finding novel therapeutic targets in epilepsy to improve the management and treatment outcomes of patients suffering from this debilitating condition.
Purpose: This comprehensive review examines the cardiovascular (CV) impact of four key antihyperglycemic drug classes—metformin, DPP-4 inhibitors (DPP-4is), GLP-1 receptor agonists (GLP-1 RAs), and SGLT2 inhibitors (SGLT2is)—analyzing their mechanisms of action, clinical trial findings, and therapeutic applications for managing type 2 diabetes mellitus (T2DM) and reducing CV complications. Results: Metformin demonstrates CV risk reduction through pleiotropic mechanisms, though its relative effectiveness compared to newer agents requires further investigation. DPP-4i maintain CV safety in trials like TECOS and CAROLINA, though saxagliptin shows increased HF hospitalization risk in vulnerable populations, particularly those with pre-existing HF or CKD. GLP-1 Ras, especially long-acting formulations (liraglutide, semaglutide), significantly decrease major adverse cardiovascular events (MACE) and mortality rates, with dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) agonists (tirzepatide) emerging as promising therapies for heart failure with preserved ejection fraction (HFpEF). SGLT2is demonstrate consistent benefits, reducing HF hospitalizations by 24-30% and CV mortality by 38% (empagliflozin), with effects extending beyond diabetic populations. Conclusions: Contemporary T2DM management emphasizes organ-protective strategies. While GLP-1 RAs and SGLT2is provide substantial CV advantages, DPP-4is necessitate careful patient selection. Metformin retains its fundamental role, though direct comparisons with newer agents are needed. Tailored treatment plans, incorporating pharmacological mechanisms and individual risk assessment, are crucial for optimizing CV outcomes in T2DM patients. Keywords; Metformin; DPP-4i; GLP-1RAs; SGLT2i; Type 2 diabetes; cardiovascular outcome trials
Medicinal plants play a crucial role in the healthcare systems globally, not only for their medicinal purposes but also as for their nutraceutical potential; Recently, there is a trending interest in medicinal natural products and their conducive incorporation in daily diet. There is a rising need to further investigate and unveil the unexploited medicinal plants. A solid example is Lepidium sativum plant (garden cress or Hab El-Rashad). It’s an Egyptian native edible herb with many traditional and medicinal noteworthy benefits. This article comprehends the traditional, medicinal, biological, agricultural, economic, pharmaceutical and industrial abilities of this whole plant. This review highlights its nutraceutical use, dietary consumption, upscaling its cultivation and pharmaceutical utilization in Egypt. Also, this review provide an established base for upcoming researches to productively resume investigating hidden unconfirmed traditional potentials. In addition to, scrutinizing quality control measures, herbal standardization for market formulation, bioavailability, pharmacokinetic and clinical studies in human.
Alpinia zerumbet is an economically important species that belongs to the family Zingiberaceae. It is widely used in traditional medicines and nutraceuticals. This study explores the phytochemical constituents of the extracts of both leaves and rhizomes of A. zerumbet together with their in-vitro anticholinesterase effect. Using the LC/MS-MS technique, both leaves and rhizomes of A. zerumbet were analyzed leading to the annotation of 24 constituents in the methanolic extract of the leaves and 23 constituents in the rhizomes extract encompassing various classes including phenolic acids, flavonoids, kavalactones, diarylheptanoids, gingerols and terpenoids. Both extracts demonstrated promising anticholinesterase activity, with the rhizomes exhibiting a stronger effect (IC50 = 2.229 ± 0.077 µg/mL) compared to the leaves (IC50 = 3.573 ± 0.123 µg/mL). Tacrine served as the standard for anticholinesterase activity, with an IC50 = 0.428 ± 0.015 µg/mL. The results suggest that A. zerumbet, particularly its rhizomes, holds potential as a natural source of anticholinesterase agents, warranting further investigation for therapeutic applications.
Workers are increasingly being exposed to the fumes of toluene, which is used extensively in many industrial processes. Toluene exposure has been connected to heart disorders such as ventricular tachycardia, coronary vasospasm, sinus bradycardia, and atrioventricular conduction difficulties. Alpha lipoic acid (ALA) and L-carnitine (LC) are antioxidants that may have cardioprotective benefits against chronic cardiotoxicity caused by toluene in male rats, therefore this study investigates these effects over a month in male rats. Toluene was administered for one month to male Sprague Dawley rats. ALA (50 and 100 mg/kg i.p.) and LC (150 mg/kg and 300 mg/kg i.p.) were administered during the last 15 days of treatment. Treatment with antioxidants had a strong therapeutic impact against myocardial damage caused by toluene, as evidenced by elevated levels of cardiotoxicity markers: The isoenzyme CK-MB (creatine kinase) and LDH (lactate dehydrogenase). Toluene significantly reduced glutathione levels, increased lipid peroxidation, and decreased the activities of glutathione reductase (GR) and glutathione peroxidase (GPx), antioxidant enzymes that are markers of oxidative stress. ALA and LC treatment significantly attenuated toluene-mediated-cardiac damage as well as oxidative damage, with LC being more effective than ALA. Furthermore, toluene induced apoptotic cardiac damage as evidenced by increased caspase-3 and caspase-12 activities. ALA and LC treatment attenuated these apoptotic actions of toluene. In addition, toluene increased calpain-2 activity, while ALA and LC ameliorated this effect. All of these results suggest that ALA and LC have a strong protective effect against the cardiotoxic effects of toluene by reducing oxidative stress, apoptotic tissue damage, and calpain-2 activity.
Aspergillus flocculosus represents a relatively recent fungal source of interesting secondary metabolites. A. flocculosus, as a fungal endophyte, had been isolated from different sources including plants as Markhamia platycaly, sponges for example Phakellia fusca, algae for example Padina sp. as well as sea sediment. This review presents a literature survey for the reported secondary metabolites isolated from A. flocculosus, demonstrating the potential biological activities of the reported metabolites. This review presents a comprehensive literature survey of the secondary metabolites isolated from the fungus A. flocculosus reporting eighty secondary metabolites belonging to different chemical classes including: steroids, meroterpenoids and diketopiperazine alkaloids, drimane sesquiterpenoids as well as their nitro benzoyl derivatives as well as cerebrosides. Secondary metabolites reported from A. flocculosus possess numerous biological activities including anticancer, anti-inflammatory, anti-trypanosomal, antimicrobial and neuroprotective activities. Despite the relatively limited reports for secondary metabolites represented in this review, the chemical diversity and the potential biological activities of the reported metabolites reported herein encourages for further in depth research for novel bioactive secondary metabolites from A. flocculosus especially those derived as endophytes from marine resources.
Introduction: Colorectal cancer (CRC) is the second-leading cause of mortality and morbidity worldwide with multiple standard therapies that failed to improve outcomes. Metformin, an old, repurposed medication with pleiotropic effect in a number of cancers, arise as a possible treatment for CRC. This review aimed to assess the effect of metformin in addition to the treatment plan of CRC patients. Methods: To identify relevant studies, Google scholar, PubMed, Egyptian knowledge bank (EKB) and clinical trial.gov were systematically searched. Pre-defined search keywords were used as “Metformin”, “colorectal cancer”, “randomized controlled trials”, “interventional studies”, “observational studies”. Only English-based trials that are in full text were included. Results: A total of 20 studies with different therapeutic adjuvant treatment options were evaluated for metformin treatment effect in CRC. Randomized control trials and observational studies were the main interest of the review while preventive and pre-clinical studies including animals and cell lines were excluded. Conclusion: Most of the studies except few showed promising results on overall survival (OS), disease free survival, relapse-free time for metformin use as treatment in CRC. Also, a reductive effect of metformin was shown in toxicities as oxaliplatin-induced peripheral neuropathy and poor prognostic features as vessel co-option vasculature in liver metastasis. Future clinical randomized controlled studies are essential to confirm these results.
Many people have always aspired to have skin that is young-looking and vibrant. The natural aging process of the skin, which is impacted by both internal and external factors, has sparked further research into its origins and the creation of efficient therapeutic approaches. This review aims to give a thorough understanding of the skin's composition, the causes and variables that contribute to skin aging, the difficulties in treating skin aging, and the methods used to treat skin aging. It will also go into detail about the obstacles antioxidants face while trying to permeate the skin and their potential role as essential players in the fight against skin aging. In addition, it will discuss the intriguing use of nanoparticles (NPs) in reversing skin aging, emphasizing their involvement in enhanced skin penetration. Due to their distinct size-dependent characteristics and ability to integrate medicines, NPs in general provide a variety of therapeutic benefits for antioxidant drug delivery to control skin aging.
Aim: This study aimed to investigate the association of different patient factors on the occurrence of diabetic peripheral neuropathy (DPN) among type 2 diabetes mellitus patients. Methods: A case-control study was conducted on a total sample of 180 Egyptian type 2 diabetic patients. A full medical, medication, social, and family history was collected for the recruited sample. Glycated hemoglobin, lipid profile, and microalbuminuria were assessed. Results: Among 180 patients recruited, 52 patients suffered from DPN. Low density-lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were higher among patients suffering from DPN (p-value = 0.007 and 0.005, respectively). Metformin usage was the only factor that showed a significant decrease in the odds of developing DPN (odds ratio= 0.511, 95% confidence interval= 0.264- 0.911). Subgroup analysis showed that metformin decreased DPN among males rather than females (p-value = 0.006 vs 0.616, respectively). Conclusion: Serum LDL-C and TC are both determinants for increased risk of DPN among type 2 diabetic patients. Metformin usage decreases DPN in a sex-specific dimorphic fashion where females are less liable to the protective effect of metformin against DPN.
