Previous
Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis, are characterized by multifactorial pathologies that extend beyond neuronal loss to include neuroinflammation, oxidative stress, mitochondrial dysfunction, and glial dysregulation. Despite extensive research, disease-modifying therapies remain elusive, hindered by late diagnosis, limited availability of specific biomarkers, and the persistent dominance of reductionist, single-target strategies. This comprehensive and informative review provides a critical synthesis of integrated neuroprotective strategies, with particular focus on glial mechanisms and biomarker-guided interventions. Therapeutic emphasis is placed on coordinated mechanisms targeting both neurons and non-neuronal cells, such as astrocytes, microglia, and oligodendrocytes. Emerging strategies are reported to include modulation of synaptic plasticity and neurotransmission, delivery of neurotrophic factors, activation of intrinsic cytoprotective pathways (e.g., Nrf2 signaling), restoration of proteostasis, and induction of regeneration via cellular reprogramming. Glial cells are discussed as therapeutic targets involved in inflammation, metabolism, myelination, and neuronal survival. Advances in predictive, preventive, personalized, and participatory (P4) medicine, supported by genomics, multi-omics, imaging, and real-world data, are presented as accelerating biomarker discovery and enabling earlier and more precise stage-specific interventions. Future success in combating neurodegeneration will depend on integrated approaches that combine protective, supportive, and regenerative strategies, appropriate for disease stage and patient profile. By reframing neuroprotection as a systemic, multicellular endeavor, this review highlights the potential to not only extend life expectancy, but also preserve meaningful quality of life in individuals affected by neurodegenerative diseases.
Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis, are characterized by multifactorial pathologies that extend beyond neuronal loss to include neuroinflammation, oxidative stress, mitochondrial dysfunction, and glial dysregulation. Despite extensive research, disease-modifying therapies remain elusive, hindered by late diagnosis, limited availability of specific biomarkers, and the persistent dominance of reductionist, single-target strategies. This comprehensive and informative review provides a critical synthesis of integrated neuroprotective strategies, with particular focus on glial mechanisms and biomarker-guided interventions. Therapeutic emphasis is placed on coordinated mechanisms targeting both neurons and non-neuronal cells, such as astrocytes, microglia, and oligodendrocytes. Emerging strategies are reported to include modulation of synaptic plasticity and neurotransmission, delivery of neurotrophic factors, activation of intrinsic cytoprotective pathways (e.g., Nrf2 signaling), restoration of proteostasis, and induction of regeneration via cellular reprogramming. Glial cells are discussed as therapeutic targets involved in inflammation, metabolism, myelination, and neuronal survival. Advances in predictive, preventive, personalized, and participatory (P4) medicine, supported by genomics, multi-omics, imaging, and real-world data, are presented as accelerating biomarker discovery and enabling earlier and more precise stage-specific interventions. Future success in combating neurodegeneration will depend on integrated approaches that combine protective, supportive, and regenerative strategies, appropriate for disease stage and patient profile. By reframing neuroprotection as a systemic, multicellular endeavor, this review highlights the potential to not only extend life expectancy, but also preserve meaningful quality of life in individuals affected by neurodegenerative diseases.
DOI: https://doi.org/10.37349/ent.2026.1004136
Aim:
The aim of this study is to compare the accuracy, reliability, and educational quality of YouTube videos on osteochondritis dissecans based on their YouTube Health verification status.
Methods:
The term “osteochondritis dissecans” was searched on June 3, 2024. The first 50 videos found on YouTube after searching “osteochondritis dissecans” were evaluated. The Journal of the American Medical Association (JAMA) benchmark criteria was used to score video reliability and accuracy (0–4 points), the Global Quality Score (GQS) was used to score nonspecific educational content (0–5 points), and the osteochondritis dissecans specific score (OCDSS) was used to score specific educational content (0–11 points). Three independent reviewers scored all videos, and interrater reliability was assessed with intraclass correlation coefficients (ICC). Group differences were analyzed with one-way analysis of variance (ANOVA) and independent sample t-tests, and multivariable linear regression was used to identify independent predictors of JAMA, GQS, and OCDSS scores.
Results:
A total of 50 videos were analyzed with a cumulative 326,851 views. The mean JAMA score was 2.28 ± 0.64, the mean GQS score was 2.60 ± 1.36, and the mean OCDSS was 5.02 ± 3.16. The mean JAMA score for YouTube Health verified videos was 2.44 ± 0.34, GQS was 2.72 ± 1.22, and OCDSS was 5.72 ± 2.69. The mean JAMA score for videos not verified by YouTube Health was 2.29 ± 0.65, GQS score was 2.61 ± 1.44, and OCDSS was 4.95 ± 3.37. These differences were not statistically significant: JAMA p = 0.380, GQS p = 0.837, OCDSS p = 0.546.
Conclusions:
There were no significant differences in reliability, educational content, and comprehensiveness between videos that were verified by YouTube Health and videos that were not verified.
Aim:
The aim of this study is to compare the accuracy, reliability, and educational quality of YouTube videos on osteochondritis dissecans based on their YouTube Health verification status.
Methods:
The term “osteochondritis dissecans” was searched on June 3, 2024. The first 50 videos found on YouTube after searching “osteochondritis dissecans” were evaluated. The Journal of the American Medical Association (JAMA) benchmark criteria was used to score video reliability and accuracy (0–4 points), the Global Quality Score (GQS) was used to score nonspecific educational content (0–5 points), and the osteochondritis dissecans specific score (OCDSS) was used to score specific educational content (0–11 points). Three independent reviewers scored all videos, and interrater reliability was assessed with intraclass correlation coefficients (ICC). Group differences were analyzed with one-way analysis of variance (ANOVA) and independent sample t-tests, and multivariable linear regression was used to identify independent predictors of JAMA, GQS, and OCDSS scores.
Results:
A total of 50 videos were analyzed with a cumulative 326,851 views. The mean JAMA score was 2.28 ± 0.64, the mean GQS score was 2.60 ± 1.36, and the mean OCDSS was 5.02 ± 3.16. The mean JAMA score for YouTube Health verified videos was 2.44 ± 0.34, GQS was 2.72 ± 1.22, and OCDSS was 5.72 ± 2.69. The mean JAMA score for videos not verified by YouTube Health was 2.29 ± 0.65, GQS score was 2.61 ± 1.44, and OCDSS was 4.95 ± 3.37. These differences were not statistically significant: JAMA p = 0.380, GQS p = 0.837, OCDSS p = 0.546.
Conclusions:
There were no significant differences in reliability, educational content, and comprehensiveness between videos that were verified by YouTube Health and videos that were not verified.
DOI: https://doi.org/10.37349/edht.2026.101176
Vaccines have eliminated once-deadly diseases, yet rising vaccine hesitancy threatens these gains. Human papillomavirus (HPV) illustrates this crisis: Although it is one of the few vaccines that directly prevents cancer, uptake remains low in the United States and globally, particularly in regions with high cervical cancer incidence. This persistent gap undermines both individual and public health. This paper examines how digital health technologies, aligned with policy frameworks and community engagement, can address HPV vaccine hesitancy. We propose the Digital Vaccine Advocacy Toolkit, a structured, HPV-focused framework that integrates electronic health record (EHR)-based clinical decision support, personalized reminders, population dashboards, AI-driven misinformation surveillance, and culturally tailored education. As a conceptual model, it draws on secondary evidence and policy recommendations rather than original empirical data, emphasizing interoperability, privacy safeguards, equity-driven design, and stakeholder engagement to support feasibility across diverse health systems. The Toolkit is organized into illustrative workflows that demonstrate how technical features could be combined with policy mechanisms and financing models to strengthen HPV vaccination. By situating HPV within the World Health Organization’s 90-70-90 elimination targets and the recent adoption of single-dose schedules, the framework highlights both translational relevance and global applicability, though its recommendations require pilot testing and empirical validation. Overall, the Digital Vaccine Advocacy Toolkit offers a practical roadmap for improving HPV vaccine uptake through the integration of technology, policy, and ethics, and provides a transferable model for advancing digital health strategies to increase vaccine confidence and equity in immunization programs worldwide.
Vaccines have eliminated once-deadly diseases, yet rising vaccine hesitancy threatens these gains. Human papillomavirus (HPV) illustrates this crisis: Although it is one of the few vaccines that directly prevents cancer, uptake remains low in the United States and globally, particularly in regions with high cervical cancer incidence. This persistent gap undermines both individual and public health. This paper examines how digital health technologies, aligned with policy frameworks and community engagement, can address HPV vaccine hesitancy. We propose the Digital Vaccine Advocacy Toolkit, a structured, HPV-focused framework that integrates electronic health record (EHR)-based clinical decision support, personalized reminders, population dashboards, AI-driven misinformation surveillance, and culturally tailored education. As a conceptual model, it draws on secondary evidence and policy recommendations rather than original empirical data, emphasizing interoperability, privacy safeguards, equity-driven design, and stakeholder engagement to support feasibility across diverse health systems. The Toolkit is organized into illustrative workflows that demonstrate how technical features could be combined with policy mechanisms and financing models to strengthen HPV vaccination. By situating HPV within the World Health Organization’s 90-70-90 elimination targets and the recent adoption of single-dose schedules, the framework highlights both translational relevance and global applicability, though its recommendations require pilot testing and empirical validation. Overall, the Digital Vaccine Advocacy Toolkit offers a practical roadmap for improving HPV vaccine uptake through the integration of technology, policy, and ethics, and provides a transferable model for advancing digital health strategies to increase vaccine confidence and equity in immunization programs worldwide.
DOI: https://doi.org/10.37349/edht.2026.101177
Aim:
The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Methods:
Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS).
Results:
S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison, L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity.
Conclusions:
Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects of S. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation.
Aim:
The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Methods:
Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS).
Results:
S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison, L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity.
Conclusions:
Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects of S. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation.
DOI: https://doi.org/10.37349/ei.2025.1003233
This article belongs to the special issue Immunology and Pain
Aim:
This study examined differences in attentional control and awareness of interference among children with attention-deficit/hyperactivity disorder (ADHD), children with subthreshold ADHD (children showing some but not all symptoms required for diagnosis), and children with typical development. Specifically, we investigated how visual and auditory distractions affect behavioral performance and eye movements, to clarify the degree and nature of attentional control impairments associated with subthreshold versus clinically diagnosed ADHD.
Methods:
One hundred and two children (mean age = 7.23 years, SD = 1.23; 34 per group) participated in three eye-tracking tasks involving a bouncing ball under no, visual, and auditory interference. Behavioral accuracy (number of correctly counted bounces), fixation duration on the target, gaze reorientation latency, and distractor awareness were analyzed using mixed-design analyses of variance (ANOVAs) and chi-square tests.
Results:
Significant group differences were found in counting accuracy, F(2, 99) = 16.42, p = 0.00069, η2p = 0.245, with typically developing children performing best, followed by those with subthreshold and full ADHD. Eye-tracking indices showed a similar gradient: fixation duration decreased with symptom severity, F(4, 198) = 7.65, p = 0.00094, η2p = 0.134, while gaze reorientation latency increased, F(2, 99) = 12.18, p = 0.00093, η2p = 0.197 (typical development ≈ 480 ms; subthreshold ≈ 621 ms; ADHD ≈ 721 ms). Awareness of distractors also varied significantly across groups, χ2(2, n = 102) = 38.12, p < 0.001, Cramer’s V = 0.61, with detection rates of approximately 80% (typical development), 50% (subthreshold), and 25% (ADHD).
Conclusions:
Both children with ADHD and children with subthreshold ADHD show measurable deficits in attentional control and awareness of interference, particularly under visual and auditory distraction. Children with subthreshold ADHD exhibited an intermediate profile, supporting a continuum rather than a categorical distinction in cognitive control impairments. These findings highlight the importance of early identification and interventions targeting attentional regulation and metacognitive monitoring across the ADHD spectrum.
Aim:
This study examined differences in attentional control and awareness of interference among children with attention-deficit/hyperactivity disorder (ADHD), children with subthreshold ADHD (children showing some but not all symptoms required for diagnosis), and children with typical development. Specifically, we investigated how visual and auditory distractions affect behavioral performance and eye movements, to clarify the degree and nature of attentional control impairments associated with subthreshold versus clinically diagnosed ADHD.
Methods:
One hundred and two children (mean age = 7.23 years, SD = 1.23; 34 per group) participated in three eye-tracking tasks involving a bouncing ball under no, visual, and auditory interference. Behavioral accuracy (number of correctly counted bounces), fixation duration on the target, gaze reorientation latency, and distractor awareness were analyzed using mixed-design analyses of variance (ANOVAs) and chi-square tests.
Results:
Significant group differences were found in counting accuracy, F(2, 99) = 16.42, p = 0.00069, η2p = 0.245, with typically developing children performing best, followed by those with subthreshold and full ADHD. Eye-tracking indices showed a similar gradient: fixation duration decreased with symptom severity, F(4, 198) = 7.65, p = 0.00094, η2p = 0.134, while gaze reorientation latency increased, F(2, 99) = 12.18, p = 0.00093, η2p = 0.197 (typical development ≈ 480 ms; subthreshold ≈ 621 ms; ADHD ≈ 721 ms). Awareness of distractors also varied significantly across groups, χ2(2, n = 102) = 38.12, p < 0.001, Cramer’s V = 0.61, with detection rates of approximately 80% (typical development), 50% (subthreshold), and 25% (ADHD).
Conclusions:
Both children with ADHD and children with subthreshold ADHD show measurable deficits in attentional control and awareness of interference, particularly under visual and auditory distraction. Children with subthreshold ADHD exhibited an intermediate profile, supporting a continuum rather than a categorical distinction in cognitive control impairments. These findings highlight the importance of early identification and interventions targeting attentional regulation and metacognitive monitoring across the ADHD spectrum.
DOI: https://doi.org/10.37349/ent.2025.1004134
This article belongs to the special issue Advances in the Pathogenesis, Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder
Aim:
Neurodegenerative diseases, such as Alzheimer’s, are strongly associated with amyloid-β aggregation. This study aimed to explore bioactive metabolites from endophytic bacteria as potential anti-aggregation agents with relevance to neuroprotection, focusing on isolate D11 obtained from a geothermal fern at Gedong Songo hot springs.
Methods:
Isolate D11 was characterized by Gram staining and 16S rRNA sequencing. Growth curve analysis was conducted to determine metabolite production phases. Phytochemical screening, bovine serum albumin (BSA) aggregation inhibition assays, liquid chromatography mass spectroscopy (LCMS) profiling, and molecular docking against amyloid-β were employed to evaluate bioactivity and metabolite composition.
Results:
D11 was identified as a Gram-negative rod with 97.94% similarity to Stutzerimonas stutzeri. Metabolite production peaked during the stationary and death phases. Phytochemical tests revealed alkaloids and tannins in aqueous fractions. BSA aggregation inhibition assays demonstrated potent inhibitory activity, with IC50 values (2.40–3.29 µg/mL) significantly lower than quercetin. LCMS profiling identified diverse metabolites, dominated by flavonoid glycosides such as kaempferol-7-O-deoxyhexosyl-3-O-acetylhexoside, along with alkaloids, peptides, and diterpenoids. Molecular docking confirmed strong binding affinities of flavonoid glycosides to amyloid β (–7.6 kcal/mol), outperforming quercetin (–6.0 kcal/mol).
Conclusions:
These findings suggest that isolate D11 Stutzerimonas produces bioactive metabolites with anti-aggregation activity and potential relevance to neuroprotection. However, since Stutzerimonas-derived metabolites remain poorly explored and the docking results are tentative, further in-depth characterization and in vivo validation are required to confirm their therapeutic relevance, and further validation using amyloid-β or α-synuclein models is required to confirm therapeutic implications.
Aim:
Neurodegenerative diseases, such as Alzheimer’s, are strongly associated with amyloid-β aggregation. This study aimed to explore bioactive metabolites from endophytic bacteria as potential anti-aggregation agents with relevance to neuroprotection, focusing on isolate D11 obtained from a geothermal fern at Gedong Songo hot springs.
Methods:
Isolate D11 was characterized by Gram staining and 16S rRNA sequencing. Growth curve analysis was conducted to determine metabolite production phases. Phytochemical screening, bovine serum albumin (BSA) aggregation inhibition assays, liquid chromatography mass spectroscopy (LCMS) profiling, and molecular docking against amyloid-β were employed to evaluate bioactivity and metabolite composition.
Results:
D11 was identified as a Gram-negative rod with 97.94% similarity to Stutzerimonas stutzeri. Metabolite production peaked during the stationary and death phases. Phytochemical tests revealed alkaloids and tannins in aqueous fractions. BSA aggregation inhibition assays demonstrated potent inhibitory activity, with IC50 values (2.40–3.29 µg/mL) significantly lower than quercetin. LCMS profiling identified diverse metabolites, dominated by flavonoid glycosides such as kaempferol-7-O-deoxyhexosyl-3-O-acetylhexoside, along with alkaloids, peptides, and diterpenoids. Molecular docking confirmed strong binding affinities of flavonoid glycosides to amyloid β (–7.6 kcal/mol), outperforming quercetin (–6.0 kcal/mol).
Conclusions:
These findings suggest that isolate D11 Stutzerimonas produces bioactive metabolites with anti-aggregation activity and potential relevance to neuroprotection. However, since Stutzerimonas-derived metabolites remain poorly explored and the docking results are tentative, further in-depth characterization and in vivo validation are required to confirm their therapeutic relevance, and further validation using amyloid-β or α-synuclein models is required to confirm therapeutic implications.
DOI: https://doi.org/10.37349/ent.2025.1004135
This article belongs to the special issue Natural Products in Neurotherapeutic Applications
Aim:
Hepatocellular carcinoma (HCC) accounts for 90% of liver tumors and is the fourth leading cause of cancer-related deaths worldwide. Current treatments have poor outcomes for HCC, highlighting the urgent need for new and effective therapies. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, regulates differentiation, proliferation, and migration processes, effects observed in cancer, including HCC. In this study, we aimed to investigate the chemosensitizing effects on human liver cancer cells.
Methods:
We pre-treated Huh7 and Hep3B cells with GDF11 50 ng/mL for 72 h in the presence of sorafenib (Sfb) or cisplatin (CDDP) and evaluated cellular response.
Results:
Pre-treatment with GDF11 lowered the IC50 of CDDP and Sfb in Huh7 cells. Similar effects were observed in Hep3B cells. Additionally, combining GDF11 with CDDP or Sfb significantly reduced cell viability and decreased the size and number of spheroids. Furthermore, we found that the chemosensitizing effect is initiated by GDF11 binding to the type I receptor ALK5. Inhibition of ALK5 abolished SMAD2 activation, impacting the chemosensitizing effects. Finally, GDF11, combined with Sfb or CDDP, reduced the activity of drug transporters MRP2, MRP3, and MRP4, which explains its chemosensitizing properties.
Conclusions:
GDF11 increases the sensitivity of HCC-derived cell lines to Sfb and CDDP by modulating the drug-efflux transporters MRP2, MRP3, and MRP4.
Aim:
Hepatocellular carcinoma (HCC) accounts for 90% of liver tumors and is the fourth leading cause of cancer-related deaths worldwide. Current treatments have poor outcomes for HCC, highlighting the urgent need for new and effective therapies. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, regulates differentiation, proliferation, and migration processes, effects observed in cancer, including HCC. In this study, we aimed to investigate the chemosensitizing effects on human liver cancer cells.
Methods:
We pre-treated Huh7 and Hep3B cells with GDF11 50 ng/mL for 72 h in the presence of sorafenib (Sfb) or cisplatin (CDDP) and evaluated cellular response.
Results:
Pre-treatment with GDF11 lowered the IC50 of CDDP and Sfb in Huh7 cells. Similar effects were observed in Hep3B cells. Additionally, combining GDF11 with CDDP or Sfb significantly reduced cell viability and decreased the size and number of spheroids. Furthermore, we found that the chemosensitizing effect is initiated by GDF11 binding to the type I receptor ALK5. Inhibition of ALK5 abolished SMAD2 activation, impacting the chemosensitizing effects. Finally, GDF11, combined with Sfb or CDDP, reduced the activity of drug transporters MRP2, MRP3, and MRP4, which explains its chemosensitizing properties.
Conclusions:
GDF11 increases the sensitivity of HCC-derived cell lines to Sfb and CDDP by modulating the drug-efflux transporters MRP2, MRP3, and MRP4.
DOI: https://doi.org/10.37349/edd.2025.1005108
The evolution of nanocarrier-based drug delivery systems has transformed the paradigm of cancer therapeutics, advancing from conventional cytotoxic formulations to intelligent, adaptive nanosystems capable of precision targeting. Early-generation nanocarriers exploited the enhanced permeability and retention (EPR) effect for passive tumor accumulation, yet their therapeutic efficiency remained constrained by tumor heterogeneity, limited penetration, and off-target toxicity. Emerging nanotechnologies now integrate active targeting, stimuli-responsive components, and biomimetic strategies to achieve spatiotemporal control over drug release and tumor-selective action. These “intelligent” nanocarriers are designed to recognize molecular signatures, respond dynamically to tumor microenvironmental cues such as pH, redox gradients, hypoxia, and enzymatic activity, and even engage in real-time feedback through imaging or biosensing modules. In addition, hybrid and multifunctional platforms—combining liposomes, micelles, dendrimers, polymeric nanoparticles, and inorganic systems—offer programmable functionality and synergistic delivery of chemotherapeutic, gene-editing, and immunomodulatory agents. This review delineates the mechanistic basis of passive and active targeting, highlights recent innovations in stimuli-responsive and biomimetic nanocarriers, and explores translational and regulatory perspectives shaping their clinical journey. By integrating nanotechnology with systems biology and artificial intelligence, next-generation nanocarriers promise to redefine the landscape of precision antitumor therapy.
The evolution of nanocarrier-based drug delivery systems has transformed the paradigm of cancer therapeutics, advancing from conventional cytotoxic formulations to intelligent, adaptive nanosystems capable of precision targeting. Early-generation nanocarriers exploited the enhanced permeability and retention (EPR) effect for passive tumor accumulation, yet their therapeutic efficiency remained constrained by tumor heterogeneity, limited penetration, and off-target toxicity. Emerging nanotechnologies now integrate active targeting, stimuli-responsive components, and biomimetic strategies to achieve spatiotemporal control over drug release and tumor-selective action. These “intelligent” nanocarriers are designed to recognize molecular signatures, respond dynamically to tumor microenvironmental cues such as pH, redox gradients, hypoxia, and enzymatic activity, and even engage in real-time feedback through imaging or biosensing modules. In addition, hybrid and multifunctional platforms—combining liposomes, micelles, dendrimers, polymeric nanoparticles, and inorganic systems—offer programmable functionality and synergistic delivery of chemotherapeutic, gene-editing, and immunomodulatory agents. This review delineates the mechanistic basis of passive and active targeting, highlights recent innovations in stimuli-responsive and biomimetic nanocarriers, and explores translational and regulatory perspectives shaping their clinical journey. By integrating nanotechnology with systems biology and artificial intelligence, next-generation nanocarriers promise to redefine the landscape of precision antitumor therapy.
DOI: https://doi.org/10.37349/etat.2025.1002355
Age-related neurological disorders such as ALS (Lou Gehrig’s disease), Parkinson’s disease, and Alzheimer’s disease have few truly effective treatment options. At best, these may slow the inexorable disease progression without providing a cure. Part of the problem with therapeutic approaches may arise due to the stage at which these diseases are detected, particularly the sporadic forms. In most cases, early signs and symptoms may be insidious, thus hiding the significant damage done to the areas of the nervous system impacted prior to any firm clinical diagnosis. This situation appears to necessitate the development of earlier detection methods for “biomarkers” that might allow for much earlier phase disease state treatments that might serve to significantly slow or even halt disease progression. Currently, most biomarkers in use serve primarily as aids to disease diagnosis, at which point there are no successful treatment options. In contrast, a search for more effective early treatment options would need to identify characteristic and specific molecular signatures of disease onset and progression using methods that are simple, such as blood-based analytical assays, relatively cheap, and crucially minimally invasive.
Age-related neurological disorders such as ALS (Lou Gehrig’s disease), Parkinson’s disease, and Alzheimer’s disease have few truly effective treatment options. At best, these may slow the inexorable disease progression without providing a cure. Part of the problem with therapeutic approaches may arise due to the stage at which these diseases are detected, particularly the sporadic forms. In most cases, early signs and symptoms may be insidious, thus hiding the significant damage done to the areas of the nervous system impacted prior to any firm clinical diagnosis. This situation appears to necessitate the development of earlier detection methods for “biomarkers” that might allow for much earlier phase disease state treatments that might serve to significantly slow or even halt disease progression. Currently, most biomarkers in use serve primarily as aids to disease diagnosis, at which point there are no successful treatment options. In contrast, a search for more effective early treatment options would need to identify characteristic and specific molecular signatures of disease onset and progression using methods that are simple, such as blood-based analytical assays, relatively cheap, and crucially minimally invasive.
DOI: https://doi.org/10.37349/ent.2025.1004133
Gut microbiota is critical for human immunity, metabolism, and overall well-being. Dysbiosis has been associated with a variety of diseases, including metabolic syndrome, inflammatory diseases, and neurodevelopmental issues. Kefir, a traditional fermented beverage produced with dairy or non-dairy substrates and kefir grains, contains probiotics and bioactive substances that may improve gut microbial composition. Current research indicates that kefir increases beneficial taxa such as Lactobacillus spp., Bifidobacterium spp., and Akkermansia spp., whereas decreasing pro-inflammatory microbes such as Enterobacteriaceae spp. and Clostridium spp. via antimicrobial metabolite production, competitive exclusion, prebiotic exopolysaccharides, short-chain fatty acid enhancement, immune modulation, and improved gut-barrier integrity. Furthermore, traditional kefir fermented with grains has higher microbial diversity and probiotic potential than kefir fermented with starting cultures. Despite these encouraging results, interpretation is constrained by variations in kefir production, dosage, intervention duration, and microbiota analysis methods; therefore, this review aims to evaluate how kefir modulates gut microbiota composition in human and animal models.
Gut microbiota is critical for human immunity, metabolism, and overall well-being. Dysbiosis has been associated with a variety of diseases, including metabolic syndrome, inflammatory diseases, and neurodevelopmental issues. Kefir, a traditional fermented beverage produced with dairy or non-dairy substrates and kefir grains, contains probiotics and bioactive substances that may improve gut microbial composition. Current research indicates that kefir increases beneficial taxa such as Lactobacillus spp., Bifidobacterium spp., and Akkermansia spp., whereas decreasing pro-inflammatory microbes such as Enterobacteriaceae spp. and Clostridium spp. via antimicrobial metabolite production, competitive exclusion, prebiotic exopolysaccharides, short-chain fatty acid enhancement, immune modulation, and improved gut-barrier integrity. Furthermore, traditional kefir fermented with grains has higher microbial diversity and probiotic potential than kefir fermented with starting cultures. Despite these encouraging results, interpretation is constrained by variations in kefir production, dosage, intervention duration, and microbiota analysis methods; therefore, this review aims to evaluate how kefir modulates gut microbiota composition in human and animal models.
DOI: https://doi.org/10.37349/eff.2025.1010107
Aim:
Parkinson’s disease (PD) and Alzheimer’s disease (AD) represent critical neurological disorders that have emerged as significant health concerns in the 21st century. The pharmacological interventions currently employed to manage these diseases demonstrate limited efficacy and some adverse side effects. Historically, natural products have been used to develop therapeutic agents targeting neurodegenerative disorders. This study aimed to apply in silico techniques to investigate the pharmacological mechanisms of capsaicin as a possible alternative treatment or coadjutant phytotherapy for PD and AD.
Methods:
We obtained target genes for capsaicin, PD, and AD from the HERB database, the Swiss Target Prediction database, the Comparative Toxicogenomics Database, and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and matched them. Subsequently, we constructed a protein-protein interaction network and performed enrichment analysis of the common targets. Then, the interactions of capsaicin with the proteins with the highest degree were tested using molecular docking. The stability of the complexes was verified using molecular dynamics techniques.
Results:
A total of 25 targets were found in common from the databases for capsaicin, AD, and PD. The enrichment analysis revealed that proteins from these targets influenced integrin activity in the IGF1-IGF1R complex, cholinesterase activity, and dopamine neurotransmitter receptor activity, all of which are coupled via protein Gi/Go, among other cellular processes. From the protein-protein interaction network, we identified the hub proteins IL6, GSK3B, CASP, BCL2, ESR1, SIRT1, NGF, IGF1, and HMOX1. Furthermore, molecular docking studies between hub proteins and capsaicin showed strong binding affinity. Finally, molecular dynamics simulations support a stable interaction between capsaicin and SIRT1, ESR1, HMOX1, and NGF.
Conclusions:
This work contributes to understanding the neuroprotective activity of capsaicin in PD and AD. However, these bioinformatic predictions require further experimental validation.
Aim:
Parkinson’s disease (PD) and Alzheimer’s disease (AD) represent critical neurological disorders that have emerged as significant health concerns in the 21st century. The pharmacological interventions currently employed to manage these diseases demonstrate limited efficacy and some adverse side effects. Historically, natural products have been used to develop therapeutic agents targeting neurodegenerative disorders. This study aimed to apply in silico techniques to investigate the pharmacological mechanisms of capsaicin as a possible alternative treatment or coadjutant phytotherapy for PD and AD.
Methods:
We obtained target genes for capsaicin, PD, and AD from the HERB database, the Swiss Target Prediction database, the Comparative Toxicogenomics Database, and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and matched them. Subsequently, we constructed a protein-protein interaction network and performed enrichment analysis of the common targets. Then, the interactions of capsaicin with the proteins with the highest degree were tested using molecular docking. The stability of the complexes was verified using molecular dynamics techniques.
Results:
A total of 25 targets were found in common from the databases for capsaicin, AD, and PD. The enrichment analysis revealed that proteins from these targets influenced integrin activity in the IGF1-IGF1R complex, cholinesterase activity, and dopamine neurotransmitter receptor activity, all of which are coupled via protein Gi/Go, among other cellular processes. From the protein-protein interaction network, we identified the hub proteins IL6, GSK3B, CASP, BCL2, ESR1, SIRT1, NGF, IGF1, and HMOX1. Furthermore, molecular docking studies between hub proteins and capsaicin showed strong binding affinity. Finally, molecular dynamics simulations support a stable interaction between capsaicin and SIRT1, ESR1, HMOX1, and NGF.
Conclusions:
This work contributes to understanding the neuroprotective activity of capsaicin in PD and AD. However, these bioinformatic predictions require further experimental validation.
DOI: https://doi.org/10.37349/ent.2025.1004132
This article belongs to the special issue Natural Products in Neurotherapeutic Applications
Diverticulitis is one of the most common gastrointestinal causes of hospitalization in Western society. While previously characterized as a disease of older patients, new literature highlights an increasing incidence among the younger population. Over the past few decades, the understanding of etiology and management of diverticulitis has changed drastically. New data refute past beliefs while promoting other novel recommendations to mitigate incidence and subsequent complications. Data now confirms the safety and possible protective benefit of particulate food, while highlighting evidence-based approaches for the use of diagnostic imaging and antibiotics. We recognize modifiable and non-modifiable risk factors that are commonly seen throughout the literature and play a significant role in the management and prevention of diverticulitis. Emerging evidence also links chronic inflammation with subsequent microbial dysbiosis and alterations in the neuroendocrine system, leading to visceral hypersensitivity and perturbation of the gut-brain axis. This review provides a comprehensive update on acute uncomplicated diverticulitis according to the most recent evidence-based literature, encompassing the risks, diagnostic modalities, and management treatment regimens.
Diverticulitis is one of the most common gastrointestinal causes of hospitalization in Western society. While previously characterized as a disease of older patients, new literature highlights an increasing incidence among the younger population. Over the past few decades, the understanding of etiology and management of diverticulitis has changed drastically. New data refute past beliefs while promoting other novel recommendations to mitigate incidence and subsequent complications. Data now confirms the safety and possible protective benefit of particulate food, while highlighting evidence-based approaches for the use of diagnostic imaging and antibiotics. We recognize modifiable and non-modifiable risk factors that are commonly seen throughout the literature and play a significant role in the management and prevention of diverticulitis. Emerging evidence also links chronic inflammation with subsequent microbial dysbiosis and alterations in the neuroendocrine system, leading to visceral hypersensitivity and perturbation of the gut-brain axis. This review provides a comprehensive update on acute uncomplicated diverticulitis according to the most recent evidence-based literature, encompassing the risks, diagnostic modalities, and management treatment regimens.
DOI: https://doi.org/10.37349/edd.2025.1005107
This article belongs to the special issue Diverticulitis: Pathomechanism, Diagnosis and Treatment
The ketogenic diet (KD) is increasingly recognized for its therapeutic benefits in managing metabolic disorders, including obesity, type 2 diabetes, and epilepsy. However, adherence to KD can elevate the body’s acid load through ketone body production, potentially leading to metabolic acidosis. Alkalinizing salts, such as sodium bicarbonate, potassium citrate, magnesium, and calcium, play a crucial role in maintaining acid-base balance and mitigating complications associated with this dietary regimen. Evidence from studies published between 2000 and 2024 highlights that these interventions can reduce acidosis-related complications, including bone demineralization, muscle cramps, and fatigue, while improving mineral balance and metabolic stability. These findings suggest that incorporating alkalinizing strategies may enhance the safety and effectiveness of KDs. Further research is needed to define optimal dosing, assess long-term safety, and develop practical clinical guidelines, particularly for vulnerable populations.
The ketogenic diet (KD) is increasingly recognized for its therapeutic benefits in managing metabolic disorders, including obesity, type 2 diabetes, and epilepsy. However, adherence to KD can elevate the body’s acid load through ketone body production, potentially leading to metabolic acidosis. Alkalinizing salts, such as sodium bicarbonate, potassium citrate, magnesium, and calcium, play a crucial role in maintaining acid-base balance and mitigating complications associated with this dietary regimen. Evidence from studies published between 2000 and 2024 highlights that these interventions can reduce acidosis-related complications, including bone demineralization, muscle cramps, and fatigue, while improving mineral balance and metabolic stability. These findings suggest that incorporating alkalinizing strategies may enhance the safety and effectiveness of KDs. Further research is needed to define optimal dosing, assess long-term safety, and develop practical clinical guidelines, particularly for vulnerable populations.
DOI: https://doi.org/10.37349/eff.2025.1010106
The most common clinical manifestation of hyperlipidemia is the formation of xanthomas, which are most often localized subcutaneously, sometimes involving tendons and ligaments, and are usually asymptomatic. A fairly rare manifestation of hyperlipidemia is hypercholesterolemic arthritis caused by cholesterol crystals. In this article, we present a case of atypical xanthoma formation in a patient in the area of the first metatarsophalangeal joint, which resembled a gouty tophus. Taking into account the presence of hyperuricemia in the blood and the “classic” lesion of the first metatarsophalangeal joint, gout was primarily suspected in the patient. The diagnosis of arthritis associated with cholesterol crystals was confirmed using the “gold standard” diagnosis of microcrystalline arthritis—crystal detection using polarization microscopy. This case gives a clear idea of how important it is not to rely solely on the clinical picture when diagnosing gout.
The most common clinical manifestation of hyperlipidemia is the formation of xanthomas, which are most often localized subcutaneously, sometimes involving tendons and ligaments, and are usually asymptomatic. A fairly rare manifestation of hyperlipidemia is hypercholesterolemic arthritis caused by cholesterol crystals. In this article, we present a case of atypical xanthoma formation in a patient in the area of the first metatarsophalangeal joint, which resembled a gouty tophus. Taking into account the presence of hyperuricemia in the blood and the “classic” lesion of the first metatarsophalangeal joint, gout was primarily suspected in the patient. The diagnosis of arthritis associated with cholesterol crystals was confirmed using the “gold standard” diagnosis of microcrystalline arthritis—crystal detection using polarization microscopy. This case gives a clear idea of how important it is not to rely solely on the clinical picture when diagnosing gout.
DOI: https://doi.org/10.37349/emd.2025.1007113
This article belongs to the special issue Evaluation and Outcomes in the Management of Gout
Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research.
Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research.
DOI: https://doi.org/10.37349/ei.2025.1003232
This article belongs to the special issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases
Neurogenetic disorders remain genetically uncharacterized in many populations, including Libya. We report three Libyan patients from two consanguineous families with pathogenic variants in sodium channel genes. Two adult sisters (Patients 1 & 2) presented with global developmental delay and progressive spastic paraparesis without epilepsy. Whole exome sequencing identified the same heterozygous SCN8A variant (c.142G>A; p.Asp48Asn) in both sisters, classified as a variant of uncertain significance (VUS). Its occurrence in two affected siblings with a consistent phenotype and the absence of other explanatory variants provide supporting evidence for its potential pathogenicity. These cases represent the first documented instances of a suspected SCN8A-related disorder in Libya. A third, unrelated 10-year-old boy (Patient 3) with a phenotype consistent with Dravet syndrome, including refractory seizures and neurodevelopmental regression, was found to harbor a likely pathogenic heterozygous SCN1A variant (c.2113del; p.Glu705Lysfs*10). This report expands the genetic and phenotypic spectrum of neurological disorders in Libya and underscores the critical role of genetic testing, while also highlighting the need for segregation studies to achieve a definitive molecular diagnosis.
Neurogenetic disorders remain genetically uncharacterized in many populations, including Libya. We report three Libyan patients from two consanguineous families with pathogenic variants in sodium channel genes. Two adult sisters (Patients 1 & 2) presented with global developmental delay and progressive spastic paraparesis without epilepsy. Whole exome sequencing identified the same heterozygous SCN8A variant (c.142G>A; p.Asp48Asn) in both sisters, classified as a variant of uncertain significance (VUS). Its occurrence in two affected siblings with a consistent phenotype and the absence of other explanatory variants provide supporting evidence for its potential pathogenicity. These cases represent the first documented instances of a suspected SCN8A-related disorder in Libya. A third, unrelated 10-year-old boy (Patient 3) with a phenotype consistent with Dravet syndrome, including refractory seizures and neurodevelopmental regression, was found to harbor a likely pathogenic heterozygous SCN1A variant (c.2113del; p.Glu705Lysfs*10). This report expands the genetic and phenotypic spectrum of neurological disorders in Libya and underscores the critical role of genetic testing, while also highlighting the need for segregation studies to achieve a definitive molecular diagnosis.
DOI: https://doi.org/10.37349/en.2025.1006120
This article belongs to the special issue Advances in Epilepsy Research
Luminescent markers have been widely used in medicine, biology, agrotechnology, and for marking nuclear wastes and consumer goods. The high sensitivity and selectivity of the markers/labels allow the detection of various substances and the obtaining of valuable information about the distribution of constituents in specific media. This review describes the state of the art in luminescent marking/labeling of various cellulose forms, including nanosized ones, cellulose derivatives, and cellulose-containing materials. The importance of this consideration is explained by the role of cellulose and its derivatives in human life and their overall impact on mankind’s development. The structure and luminescence properties of cellulose and other related materials and cellulose derivatives are discussed from the viewpoint of cellulose luminescent “self-labeling”. It is shown that dyes, organic molecules, and organic-inorganic complexes, as well as inorganic dielectric and semiconductor micro/nanoparticles, can be effectively applied for the purposes of cellulose luminescent marking/labeling. This review discusses various application examples and explains the performance and mechanisms of various systems labeling (e.g., dye-cellulose, quantum dot-cellulose complex) in these applications. The review not only comprehensively summarizes existing approaches to luminescent labeling of cellulose-containing materials. It also highlights problematic issues that arise for developers of new luminescent markers (quenching of luminescence in an aqueous environment, the need to functionalize the luminescent marker material, etc.). At the same time, this work demonstrates the prospects for luminescent labeling data in modern digital technologies, particularly in the Internet of Things (IoT).
Luminescent markers have been widely used in medicine, biology, agrotechnology, and for marking nuclear wastes and consumer goods. The high sensitivity and selectivity of the markers/labels allow the detection of various substances and the obtaining of valuable information about the distribution of constituents in specific media. This review describes the state of the art in luminescent marking/labeling of various cellulose forms, including nanosized ones, cellulose derivatives, and cellulose-containing materials. The importance of this consideration is explained by the role of cellulose and its derivatives in human life and their overall impact on mankind’s development. The structure and luminescence properties of cellulose and other related materials and cellulose derivatives are discussed from the viewpoint of cellulose luminescent “self-labeling”. It is shown that dyes, organic molecules, and organic-inorganic complexes, as well as inorganic dielectric and semiconductor micro/nanoparticles, can be effectively applied for the purposes of cellulose luminescent marking/labeling. This review discusses various application examples and explains the performance and mechanisms of various systems labeling (e.g., dye-cellulose, quantum dot-cellulose complex) in these applications. The review not only comprehensively summarizes existing approaches to luminescent labeling of cellulose-containing materials. It also highlights problematic issues that arise for developers of new luminescent markers (quenching of luminescence in an aqueous environment, the need to functionalize the luminescent marker material, etc.). At the same time, this work demonstrates the prospects for luminescent labeling data in modern digital technologies, particularly in the Internet of Things (IoT).
DOI: https://doi.org/10.37349/ebmx.2025.101353
This article belongs to the special issue Nature-Based Biomaterials for Biomedical Applications
Aim:
Community-acquired pneumonia (CAP) is a leading cause of global morbidity and mortality, and it is often treated with fluoroquinolone antibiotics. Misuse of fluoroquinolones is a known driver of antimicrobial resistance, and de-escalation of antibiotics is not only effective for patient outcomes but also reduces resistance. The aim of this study was to assess the association of fluoroquinolone de-escalation with length of stay (LOS), mortality, and other microbiological culture results in hospitalized adults with CAP.
Methods:
A retrospective cohort investigation took place with adult patients suspected of CAP in a tertiary care center in Jordan. The study examined outcomes for fluoroquinolone de-escalation that included hospital LOS, mortality, and examined the relationship between the results of microbial cultures and the outcome of de-escalation.
Results:
The study sample consisted of 125 patients with a median age of 73 years [interquartile range (IQR) = 24]. Around 65% (n = 81) of the patients were male, and 35% (n = 44) were female. The fluoroquinolone therapy was mostly levofloxacin (99.2%, n = 124). Fluoroquinolone de-escalation was medically justified in 32.8% (n = 41) of patients. When comparing the rate of successful de-escalation between those with positive and negative cultures (after the exclusion of 3 patients), positive cultures were statistically more likely to de-escalate than negative cultures, 61.5% (16/26) to 26.0% (25/96) (p = 0.002). Patients in the successful de-escalation had a statistically shorter length of hospital stay; 12 days (IQR = 8) against the failed/inappropriate group, 18 days (IQR = 11) (p = 0.004). There was no significant difference in mortality; 70.1% (n = 29) survived in the de-escalated group and 76.5% (n = 62) in the failed/inappropriate group (p = 0.514).
Conclusions:
In CAP, fluoroquinolone de-escalation may result in shorter hospital stays but does not alter mortality rates. However, limitations in establishing appropriateness for de-escalation imply the need for further studies to validate the findings.
Aim:
Community-acquired pneumonia (CAP) is a leading cause of global morbidity and mortality, and it is often treated with fluoroquinolone antibiotics. Misuse of fluoroquinolones is a known driver of antimicrobial resistance, and de-escalation of antibiotics is not only effective for patient outcomes but also reduces resistance. The aim of this study was to assess the association of fluoroquinolone de-escalation with length of stay (LOS), mortality, and other microbiological culture results in hospitalized adults with CAP.
Methods:
A retrospective cohort investigation took place with adult patients suspected of CAP in a tertiary care center in Jordan. The study examined outcomes for fluoroquinolone de-escalation that included hospital LOS, mortality, and examined the relationship between the results of microbial cultures and the outcome of de-escalation.
Results:
The study sample consisted of 125 patients with a median age of 73 years [interquartile range (IQR) = 24]. Around 65% (n = 81) of the patients were male, and 35% (n = 44) were female. The fluoroquinolone therapy was mostly levofloxacin (99.2%, n = 124). Fluoroquinolone de-escalation was medically justified in 32.8% (n = 41) of patients. When comparing the rate of successful de-escalation between those with positive and negative cultures (after the exclusion of 3 patients), positive cultures were statistically more likely to de-escalate than negative cultures, 61.5% (16/26) to 26.0% (25/96) (p = 0.002). Patients in the successful de-escalation had a statistically shorter length of hospital stay; 12 days (IQR = 8) against the failed/inappropriate group, 18 days (IQR = 11) (p = 0.004). There was no significant difference in mortality; 70.1% (n = 29) survived in the de-escalated group and 76.5% (n = 62) in the failed/inappropriate group (p = 0.514).
Conclusions:
In CAP, fluoroquinolone de-escalation may result in shorter hospital stays but does not alter mortality rates. However, limitations in establishing appropriateness for de-escalation imply the need for further studies to validate the findings.
DOI: https://doi.org/10.37349/emed.2025.1001379
DOI: https://doi.org/10.37349/ebmx.2025.101354
This article belongs to the special issue Bioinspired Material for Regenerative Medicine
Aim:
Osimertinib’s clinical application is limited by poor aqueous solubility and systemic toxicity. Nano-niosomal formulations can address these challenges by providing controlled release and enhancing delivery. To develop and systematically evaluate nano-niosomal formulations of osimertinib using different surfactants, focusing on physicochemical characteristics, release kinetics, and cytotoxic activity.
Methods:
Four niosomal formulations were prepared using Span 60, Tween 60, Pluronic F-127, and Brij 52 (each at a 1:1 cholesterol-to-surfactant ratio). Particle size, zeta potential, and entrapment efficiency were measured. In vitro drug release was analyzed using Franz diffusion cells and fitted to standard kinetic models. Cytotoxicity was assessed by MTT assay in KAIMRC-2, MDA-MB231, and HCT-116 cell lines. Vesicle morphology was visualized by transmission electron microscopy.
Results:
All nano-niosomal formulations showed nanoscale particle sizes (47–292 nm), negative zeta potentials (−18.7 to −26.5 mV), and high entrapment efficiencies (69.8%–76.2%). Release studies indicated Span 60, Tween 60, and Pluronic F-127 followed diffusion-controlled kinetics (Higuchi/Korsmeyer–Peppas model, R2 up to 0.97), while Brij 52 provided a sustained zero-order release (R2 = 0.98). Compared to free osimertinib, all niosomal systems significantly prolonged release. Cytotoxicity studies demonstrated that all formulations enhanced anti-cancer effects, with Span 60-based niosomes exhibiting the greatest potency across cell lines.
Conclusions:
Optimized nano-niosomal encapsulation of osimertinib enables sustained and controlled drug release, improved cellular uptake, and enhanced cytotoxicity in vitro. Differences in surfactant composition critically influence formulation performance, supporting the further development of niosomal osimertinib as a promising strategy for oncological drug delivery applications.
Aim:
Osimertinib’s clinical application is limited by poor aqueous solubility and systemic toxicity. Nano-niosomal formulations can address these challenges by providing controlled release and enhancing delivery. To develop and systematically evaluate nano-niosomal formulations of osimertinib using different surfactants, focusing on physicochemical characteristics, release kinetics, and cytotoxic activity.
Methods:
Four niosomal formulations were prepared using Span 60, Tween 60, Pluronic F-127, and Brij 52 (each at a 1:1 cholesterol-to-surfactant ratio). Particle size, zeta potential, and entrapment efficiency were measured. In vitro drug release was analyzed using Franz diffusion cells and fitted to standard kinetic models. Cytotoxicity was assessed by MTT assay in KAIMRC-2, MDA-MB231, and HCT-116 cell lines. Vesicle morphology was visualized by transmission electron microscopy.
Results:
All nano-niosomal formulations showed nanoscale particle sizes (47–292 nm), negative zeta potentials (−18.7 to −26.5 mV), and high entrapment efficiencies (69.8%–76.2%). Release studies indicated Span 60, Tween 60, and Pluronic F-127 followed diffusion-controlled kinetics (Higuchi/Korsmeyer–Peppas model, R2 up to 0.97), while Brij 52 provided a sustained zero-order release (R2 = 0.98). Compared to free osimertinib, all niosomal systems significantly prolonged release. Cytotoxicity studies demonstrated that all formulations enhanced anti-cancer effects, with Span 60-based niosomes exhibiting the greatest potency across cell lines.
Conclusions:
Optimized nano-niosomal encapsulation of osimertinib enables sustained and controlled drug release, improved cellular uptake, and enhanced cytotoxicity in vitro. Differences in surfactant composition critically influence formulation performance, supporting the further development of niosomal osimertinib as a promising strategy for oncological drug delivery applications.
DOI: https://doi.org/10.37349/ebmx.2025.101355
