Search Results (3,110)

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Obesity remains a major global health challenge with limited therapeutic options. Bromelain, a proteolytic enzyme complex derived from pineapple, has been recognized for its natural anti-inflammatory, anti-edematous, and appetite-suppressing properties. This study aimed to investigate the effects of bromelain on hypothalamic neuropeptides and metabolic markers in a high-fat diet (HFD)-induced obesity model in rats. Thirty-six male Wistar albino rats were randomly divided into four groups: standard diet (SD), standard diet with bromelain (SDBro), high-fat diet (HFD), and high-fat diet with bromelain (HFDBro). Obesity was induced by a 3-month HFD regimen, followed by bromelain supplementation (200 mg/kg/day, orally) for one month. Hypothalamic tissues were analyzed via ELISA for neuropeptide Y (NPY), pro-opiomelanocortin (POMC), glucose transporter 2 (GLUT2), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 receptor (IGF1R). While NPY levels showed no significant changes, POMC increased in the HFD and was normalized with bromelain. GLUT2 was downregulated in the HFD and significantly restored by bromelain. FGF2 levels remained unchanged. IGF1R was upregulated in the HFD but reduced by bromelain, with an unexpected increase in SDBro. Overall, bromelain partially reversed HFD-induced disruptions in hypothalamic energy-regulating pathways, particularly affecting GLUT2 and POMC. These findings highlight bromelain’s potential role in central metabolic regulation under dietary stress. Full article

Mycoplasma bovis is an important pathogen that is associated with respiratory diseases, mastitis, and arthritis in cattle, leading to significant economic losses in the global cattle industry. Most notably in this study, we pioneer the discovery that its secreted effector ENO1 (α-enolase) directly targets host cytoskeletal proteins for metabolic–immune regulation. Using an innovative GST pull-down/mass spectrometry approach, we made the seminal discovery of β-actin (ACTB) as the primary host target of ENO1—the first reported bacterial effector–cytoskeleton interaction mediating metabolic reprogramming. ENO1–ACTB binding depends on a hydrogen bond network involving ACTB’s 117Glu and 372Arg residues. This interaction triggers (1) glycolytic activation via Glut1 upregulation, establishing Warburg effect characteristics (lactic acid accumulation/ATP inhibition), and (2) ROS-mediated activation of dual inflammatory axes (HIF-1α/IL-1β and IL-6/TNF-α). This work establishes three groundbreaking concepts: (1) the first evidence of a pathogen effector hijacking host ACTB for metabolic manipulation, (2) a novel ‘glycolysis–ACTB–ROS-inflammation’ axis, and (3) the first demonstration of bacterial proteins coordinating a Warburg effect with cytokine storms. These findings provide new targets for anti-infection therapies against Mycoplasma bovis. Full article

In light of pressing global nutritional needs, the valorization of agri-food waste constitutes a vital strategy for enhancing human health and nutrition, while simultaneously supporting planetary health. This integrated approach is increasingly indispensable within sustainable and equitable food systems. Recently, a sustainability-driven focus has shifted attention toward the valorization of the agri-food by-products as rich sources of bioactive compounds useful in preventing or treating chronic diseases. Agri-food by-products, often regarded as waste, actually hold great potential as they are rich in bioactive components, dietary fiber, and other beneficial nutrients from which innovative food ingredients, functional foods, and even therapeutic products are developed. This review aims to provide a comprehensive analysis of the current advances in recovering and applying such compounds from agri-food waste, with a particular focus on their roles in human health, sustainable packaging, and circular economy strategies. Methods: This review critically synthesizes recent scientific literature on the extraction, characterization, and utilization of bioactive molecules from agri-food by-products. After careful analysis of the PubMed and Scopus databases, only English-language articles from the last 10 years were included in the final narrative review. The analysis also encompasses applications in the nutraceutical, pharmaceutical, and food packaging sectors. Results: Emerging technologies have enabled the efficient and eco-friendly recovery of compounds such as polyphenols, carotenoids, and dietary fibers that demonstrate antioxidant, antimicrobial, and anti-inflammatory properties. These bioactive compounds support the development of functional foods and biodegradable packaging materials. Furthermore, these valorization strategies align with global health trends by promoting dietary supplements that counteract the effects of the Western diet and chronic diseases. Conclusions: Valorization of agri-food by-products offers a promising path toward sustainable development by reducing waste, enhancing public health, and driving innovation. This strategy not only minimizes waste and supports sustainability, but also promotes a more nutritious and resilient food system. Full article

Satellite communications are pivotal to global Internet access, connectivity, and the advancement of information warfare. Despite these importance, the open nature of satellite channels makes them vulnerable to eavesdropping, making the enhancement of interception resistance in satellite communications a critical issue in both academic and industrial circles. Within the realm of satellite communications, polarization modulation and quadrature techniques are essential for information transmission and interference suppression. To boost electromagnetic countermeasures in complex battlefield scenarios, this paper integrates multi-parameter weighted-type fractional Fourier transform (MP-WFRFT) with directional modulation (DM) algorithms, building upon polarization techniques. Initially, the operational mechanisms of the polarization-amplitude-phase modulation (PAPM), MP-WFRFT, and DM algorithms are elucidated. Secondly, it introduces a novel variable polarization-amplitude-phase modulation (VPAPM) scheme that integrates variable polarization with amplitude-phase modulation. Subsequently, leveraging the VPAPM modulation scheme, an exploration of the anti-interception capabilities of MP-WFRFT through parameter adjustment is presented. Rooted in an in-depth analysis of simulation data, the anti-scanning capabilities of MP-WFRFT are assessed in terms of scale vectors in the horizontal and vertical direction. Finally, exploiting the potential of the robust anti-scanning capabilities of MP-WFRFT and the directional property of antenna arrays in DM, the paper proposes a secure transmission technique employing directional variable polarization modulation with MP-WFRFT. The performance simulation analysis demonstrates that the integration of MP-WFRFT and DM significantly outperforms individual secure transmission methods, improving anti-interception performance by at least an order of magnitude at signal-to-noise ratios above 10 dB. Consequently, this approach exhibits considerable potential and engineering significance for its application within satellite communication systems. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and currently is the second-leading cause of cancer-related mortality globally. Current front-line systemic therapies for advanced HCC offer only modest improvements in patient overall survival. HCC is a sexually dimorphic disease, and cancer progression is driven in part by AR activity. Here, we present novel niclosamide pro-drugs for use in advanced HCC based upon niclosamide’s known anti-AR activity and additional anti-cancer pathway efficacy. Methods: Niclosamide analogs were evaluated for their impacts on the AR protein in two HCC cell lines with different AR phenotypes. Amino acid conjugates of niclosamide were developed, and pharmacokinetic (PK) analyses were conducted to determine improvements in clearance and oral exposure. Finally, niclosamide analogs and amino acid conjugates were evaluated in an in vivo model of HCC. Results: Niclosamide analogs maintained anti-AR properties in HCC. Valine-conjugated niclosamide showed improved oral exposure, positioning it as a potential therapeutic in advanced HCC. Conclusions: Valine–niclosamide improves upon niclosamide’s poor solubility and oral bioavailability, increasing its utility for a variety of therapeutic uses. Further study of valine–niclosamide in advanced HCC and in other cancers or diseases is warranted. Full article

Maritime corrosion is a global problem often retarded through protective coatings containing corrosion inhibitors (CIs). ZnAl layered double hydroxides (LDH) have been used to immobilize CIs, which can reduce their early leaching and, thus, foster long-term corrosion protection. However, the environmental behavior of these nanomaterials remains largely unknown, particularly in the context of global changes. The present study aims to assess the environmental behavior of four anti-corrosion nanomaterials in an ocean acidification scenario (IPCC SSP3-7.0). Three different concentrations of the nanostructured CIs (1.23, 11.11, and 100 mg L⁻¹) were prepared and maintained at 20 °C and 30 °C in artificial salt water (ASW) at two pH values, with and without the presence of organic matter. The nanomaterials’ particle size and the release profiles of Al³⁺, Zn²⁺, and anions were monitored over time. In all conditions, the hydrodynamic size of the dispersed nanomaterials confirmed that the high ionic strength favors their aggregation/agglomeration. In the presence of organic matter, dissolved Al³⁺ increased, while Zn²⁺ decreased, and increased in the ocean acidification scenario at both temperatures. CIs were more released in the presence of humic acid. These findings demonstrate the influence of the tested parameters in the nanomaterials’ environmental behavior, leading to the release of metals and CIs. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article

Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends. Full article

Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes. The investigation focused on alterations in the vascular endothelial growth factor (VEGF) and its receptor-1 (FLT-1) signaling pathways, as well as its potential to suppress inflammation and oxidative stress. A number of rats received a single dose of streptozotocin (STZ) 55 mg/kg (i.p.) to induce DM. Sitagliptin was administered orally (100 mg/kg/90 days) to normal and diabetic rats, after which samples were collected for investigation. Sitagliptin significantly mitigated weight loss in diabetic rats. Its administration significantly reduced blood glucose levels and improved serum troponin I and CK-MB levels. Heart sections from diabetic rats showed a marked increase in mTOR, VEGF, and FLT-1 immune reaction, while sitagliptin-treated diabetic rats’ heart sections showed moderate immune reactions. Sitagliptin’s protective effect was also associated with reduced inflammation, and apoptotic markers. In conclusion, Sitagliptin is suggested to offer beneficial effects on the vascular health of cardiac blood vessels, thereby potentially reducing myocardial stress in diabetic patients. Full article

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article

Nephrolithiasis, predominantly driven by calcium oxalate (CaOx) crystal deposition, poses a significant global health burden due to its high prevalence and recurrence rates and limited preventive/therapeutic options. Recent research has underscored a pivotal role for macrophage polarization in nephrolithiasis pathogenesis. Pro-inflammatory phenotype macrophages exacerbate crystal-induced injury and foster stone formation by amplifying crystal adhesion via an NF-κB–IL-1β positive-feedback axis that sustains ROS generation and NLRP3 inflammasome activation, whereas anti-inflammatory phenotype macrophages facilitate crystal clearance and tissue repair. We have summarized the research on treating nephrolithiasis and related renal injury by targeting macrophage polarization in recent years, including therapeutic approaches through pharmacological methods, epigenetic regulation, and advanced biomaterials. At the same time, we have critically evaluated the novel therapeutic strategies for macrophage reprogramming and explored the future development directions of targeting macrophage reprogramming for nephrolithiasis treatment, such as using single-cell/spatial omics to reveal the heterogeneity of macrophages in the stone microenvironment, chimeric antigen receptor macrophages (CAR-Ms) as a potential therapy for specific crystal phagocytosis in certain areas, and multi-omics integration to address inter-patient immune differences. This review highlights that macrophage reprogramming is a transformative frontier in nephrolithiasis management and underscores the need for further research to translate these molecular insights into effective clinical applications. Full article