Search Results (4,036)

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Heart failure (HF) is a major global health challenge, characterized by high morbidity, mortality, and frequent hospital readmissions. Despite the advent of guideline-directed medical therapies (GDMTs), the burden of HF continues to grow, necessitating a shift toward comprehensive, multidisciplinary care models. Heart Failure Disease Management Programs (HF-DMPs) have emerged as structured frameworks that integrate evidence-based medical therapy, patient education, telemonitoring, and support for social determinants of health to optimize outcomes and reduce healthcare costs. This review outlines the key components of HF-DMPs, including patient identification and risk stratification, pharmacologic optimization, team-based care, transitional follow-up, remote monitoring, performance metrics, and social support systems. Incorporating tools such as artificial intelligence, pharmacist-led titration, and community health worker support, HF-DMPs represent a scalable approach to improving care delivery. The success of these programs depends on tailored interventions, interdisciplinary collaboration, and health equity-driven strategies. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Aging is a complex physiological process that profoundly affects the functionality of the musculoskeletal system, contributing to an increase in the incidence of diseases such as osteoporosis, osteoarthritis, and sarcopenia. Cellular senescence plays a crucial role in these degenerative processes, promoting chronic inflammation and tissue dysfunction through the senescence-associated secretory phenotype (SASP). Recently, senotherapeutics have shown promising results in improving musculoskeletal health. Natural compounds such as resveratrol, rapamycin, quercetin, curcumin, vitamin E, genistein, fisetin, and epicatechin act on key signaling pathways, offering protective effects against musculoskeletal decline. On the other hand, molecules such as dasatinib, navitoclax, UBX0101, panobinostat, and metformin have been shown to be effective in eliminating or modulating senescent cells. However, understanding the mechanisms of action, long-term safety, and bioavailability remain areas for further investigation. In this context, physical exercise emerges as an effective non-pharmacological countermeasure, capable of directly modulating cellular senescence and promoting tissue regeneration, representing an integrated strategy to combat age-related diseases. Therefore, we have provided an overview of the main anti-aging compounds and examined the potential of physical exercise as a strategy in the management of age-related musculoskeletal disorders. Further studies should focus on identifying synergistic combinations of pharmacological and non-pharmacological interventions to optimize the effectiveness of anti-aging strategies and promoting healthier musculoskeletal aging. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Since its discovery in the late 19th century, spinal muscular atrophy (SMA) has had a significant medical and societal impact, primarily affecting newborns, toddlers, and young adults. While new pharmaceutical strategies are effective in treating SMA in a particular subset of patients, continued research is necessary to improve the well-being of patients. Treatments are needed for those who do not respond to newly approved drugs and older patients with significantly compromised neuron systems. After summarizing SMA genotypes, phenotypes, and approved pharmacological treatments, this review presents ongoing trials for approved and new molecules, new formulations, and administration methods. Based on the work of our lab, we also discuss nutritional interventions that aim to counteract the oxidative stress present in SMA cells. Finally, we assess rehabilitative interventions, focusing on psychological approaches. Full article

Cardiorenal syndrome (CRS) is a multifactorial clinical condition characterized by the bidirectional deterioration of cardiac and renal function, driven by mechanisms such as renin–angiotensin–aldosterone system (RAAS) overactivation, systemic inflammation, oxidative stress, endothelial dysfunction, and fibrosis. The aim of this narrative review is to explore the key molecular pathways involved in CRS and to highlight emerging therapeutic approaches, with a special emphasis on nutritional interventions. We examined recent evidence on the contribution of mitochondrial dysfunction, uremic toxins, and immune activation to CRS progression and assessed the role of dietary and micronutrient factors. Results indicate that a high dietary intake of sodium, phosphorus additives, and processed foods is associated with volume overload, vascular damage, and inflammation, whereas deficiencies in potassium, magnesium, and vitamin D correlate with worse clinical outcomes. Anti-inflammatory and antioxidant bioactives, such as omega-3 PUFAs, curcumin, and anthocyanins from maqui, demonstrate potential to modulate key CRS mechanisms, including the nuclear factor kappa B (NF-κB) pathway and the NLRP3 inflammasome. Gene therapy approaches targeting endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta (TGF-β) signaling are also discussed. An integrative approach combining pharmacological RAAS modulation with personalized medical nutrition therapy and anti-inflammatory nutrients may offer a promising strategy to prevent or delay CRS progression and improve patient outcomes. Full article

Haemophilic arthropathy is caused by repeated joint bleeding episodes, primarily affecting knees, ankles and elbows. Conservative options should be considered prior to surgery, as well as postural evaluation, since any functional overload promotes the development of new bleeding. The aim of this study is to verify the use of foot orthoses in combination with postural rehabilitation, assessing the incidence of spontaneous haemarthroses and haematomas. In total, 15 patients were enrolled and randomly divided into two groups: 8 in group A, composed of patients who were prescribed foot orthoses and a 20-session rehabilitation program, and 7 in group B, composed of patients who were instructed to use foot orthoses only. All patients were evaluated at baseline (T0), at 3 months (T1—end of the rehabilitation program), and at 12 months (T2), using the following scales: Functional Independence Score in Haemophilia (FISH), Haemophilia Joint Health Score (HJHS) and Numerical Rating Scale (NRS). During the 12 months between the first and the last assessment, no patient in group A developed hemarthroses or hematomas, while one case of hemarthrosis was recorded in group B. The HJHS improved significantly (≤0.05) in group A at both T1 and T2, while in group B it improved significantly only in T2. As for FISH, it showed significant improvements in both groups at T1 and T2. NRS showed a significant reduction only at T2 in both groups (p-value T0–T1 0.3 in group A e 0.8 in group B). No patient reported any adverse effects from the use of orthotic insoles. The combination of postural rehabilitation, the use of foot orthoses and pharmacological prophylaxis could improve functioning and joint status in patients affected by haemophilic arthopathy, delaying or preventing new hemarthroses by improving the distribution of joint loads and the modification of musculoskeletal system’s characteristics. Full article

Efflux is one of the key mechanisms used by Gram-negative bacteria to reduce internal antibiotic concentrations. These active transport systems recognize and expel a wide range of toxic molecules, including antibiotics, thereby contributing to reduced antibiotic susceptibility and allowing the bacteria to acquire additional resistance mechanisms. To date, unlike other resistance mechanisms such as enzymatic modification or target mutations/masking, efflux is challenging to detect and counteract in clinical settings, and no standardized methods are currently available to diagnose or inhibit this mechanism effectively. This review first outlines the structural and functional features of major efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. It then explores various strategies used to curb their activity, with a particular focus on efflux pump inhibitors under development, detailing their structural classes, modes of action, and pharmacological potential. We discuss the main obstacles to their development, including the structural complexity and substrate promiscuity of efflux mechanisms, the limitations of current screening methods, pharmacokinetic and tissue distribution issues, and the risk of off-target toxicity. Overcoming these multifactorial barriers is essential to the rational development of less efflux-prone antibiotics or of efflux pump inhibitors. Full article

Background/Objectives: Depression is a mood disorder that causes persistent sadness and loss of interest, and its etiology involves a condition known as hypoadiponectinemia, which is prevalent in depressive individuals compared with healthy individuals and causes neuroinflammation. The use of intact adiponectin protein to target neuroinflammation in depressive moods is complex due to the difficulties associated with using the intact protein. AdipoRon, a synthetic oral adiponectin receptor agonist that targets the AdipoR1 and AdipoR2 receptors for adiponectin, has emerged in this context. Its most prominent effects include reduced inflammation and the attenuation of oxidative stress. To the best of our knowledge, no comprehensive review has addressed these results so far. To fill this literature gap, we present a comprehensive review examining the effectiveness of AdipoRon in treating depression. Methods: Only preclinical models are included due to the absence of clinical studies. Results: Analyzing the included studies shows that AdipoRon demonstrates contrasting effects against depression. However, most of the evidence underscores AdipoRon-based adiponectin replacement therapies as potential candidates for future treatment against this critical psychiatric condition due to their anti-neuroinflammatory potential, ultimately inhibiting several neuroinflammatory pathways. Conclusions: Future research endeavors must address several limitations due to the heterogeneity of the studies’ methodologies and results. Full article

Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article