Previous
Aim:
Aging is associated with reduced inhibitory control, leading to challenges in attention, decision-making, and everyday cognitive tasks. To better understand these difficulties, it is important to adopt well-designed experimental approaches that specifically assess inhibitory control mechanisms. A commonly used tool to assess how inhibitory control changes with age is the Stroop Color and Word Test, which evaluates the capacity to suppress automatic responses in favor of appropriate behavior.
Methods:
In the present study, a sample of 91 healthy individuals was examined to investigate how cognitive functions underlying Stroop task performance vary across the adult lifespan. Pearson correlations were computed between participants’ age and response times (RTs) recorded in each of the three Stroop conditions, as well as the mean RTs across all conditions. Furthermore, to assess whether these behavioral patterns were mirrored at the neurophysiological level, power spectral density (PSD) analyses were performed on resting-state electroencephalographic recordings.
Results:
In all cases, Pearson correlations were strongly significant, with stronger effects observed as task difficulty increased. At the neurophysiological level, a correlation emerged between RTs and PSD in the occipital region within the alpha 2 frequency band, which, like the behavioral effects, became progressively stronger with increasing task difficulty. In contrast, no significant correlations were observed for the alpha 1 band, suggesting that these neurophysiological changes are specific to higher alpha frequencies linked to increased cognitive demands and inhibitory control processes.
Conclusions:
These findings contribute to a better understanding of the neural mechanisms underlying age-related declines in inhibitory control and may inform the development of interventions aimed at mitigating cognitive deficits in older adults.
Aim:
Aging is associated with reduced inhibitory control, leading to challenges in attention, decision-making, and everyday cognitive tasks. To better understand these difficulties, it is important to adopt well-designed experimental approaches that specifically assess inhibitory control mechanisms. A commonly used tool to assess how inhibitory control changes with age is the Stroop Color and Word Test, which evaluates the capacity to suppress automatic responses in favor of appropriate behavior.
Methods:
In the present study, a sample of 91 healthy individuals was examined to investigate how cognitive functions underlying Stroop task performance vary across the adult lifespan. Pearson correlations were computed between participants’ age and response times (RTs) recorded in each of the three Stroop conditions, as well as the mean RTs across all conditions. Furthermore, to assess whether these behavioral patterns were mirrored at the neurophysiological level, power spectral density (PSD) analyses were performed on resting-state electroencephalographic recordings.
Results:
In all cases, Pearson correlations were strongly significant, with stronger effects observed as task difficulty increased. At the neurophysiological level, a correlation emerged between RTs and PSD in the occipital region within the alpha 2 frequency band, which, like the behavioral effects, became progressively stronger with increasing task difficulty. In contrast, no significant correlations were observed for the alpha 1 band, suggesting that these neurophysiological changes are specific to higher alpha frequencies linked to increased cognitive demands and inhibitory control processes.
Conclusions:
These findings contribute to a better understanding of the neural mechanisms underlying age-related declines in inhibitory control and may inform the development of interventions aimed at mitigating cognitive deficits in older adults.
DOI: https://doi.org/10.37349/emed.2025.1001368
This article belongs to the special issue Neurophysiological Mechanisms of Aging and Dementia
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is characterized by a high recurrence rate, limited treatment options, and frequent resistance to systemic therapy. A key factor in this resistance is the persistent activation of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that normally protects against oxidative stress but, in malignant hepatocytes, suppresses ferroptosis by restricting lipid peroxidation. This dual function positions NRF2 as a key target for therapeutic modulation in HCC. Recent preclinical studies demonstrate that NRF2 maintains tumor survival by regulating antioxidant and iron management pathways, such as GPX4, SLC7A11, and ferritin, which together mitigate lipid peroxidation and prevent ferroptotic cell death. Multiple pharmacological strategies have been evaluated to counteract this effect, including direct NRF2 inhibitors such as camptothecin (CPT) and brusatol, preoperative modulators such as metformin and picropodophyllin (PPP), and natural compounds such as tiliroside, bavaquine, and arenobufagin. These interventions often show synergistic activity with sorafenib and other standard treatments, while postoperative effectors such as CYP4F11 and the NRF2-SLC7A11-GPX4 axis have emerged as promising additional intervention points. Despite compelling results in vitro and animal model results, several challenges limit its application to clinical practice. These include the lack of dedicated clinical trials, the limited specificity of available inhibitors, tumor heterogeneity, and potential safety concerns in cirrhotic livers. Future research focuses on the development of selective NRF2 modulators, hepatocyte-targeted approaches such as proteolysis-targeted chimeras (PROTACs) and GalNAc-conjugated oligonucleotides, and biomarker-based patient stratification using genomic, immunohistochemical, and transcriptomic indicators of NRF2 activation. Taken together, contextual NRF2 modulation represents a promising strategy to restore sensitivity to ferroptosis, overcome drug resistance, and improve outcomes in HCC patients.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is characterized by a high recurrence rate, limited treatment options, and frequent resistance to systemic therapy. A key factor in this resistance is the persistent activation of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that normally protects against oxidative stress but, in malignant hepatocytes, suppresses ferroptosis by restricting lipid peroxidation. This dual function positions NRF2 as a key target for therapeutic modulation in HCC. Recent preclinical studies demonstrate that NRF2 maintains tumor survival by regulating antioxidant and iron management pathways, such as GPX4, SLC7A11, and ferritin, which together mitigate lipid peroxidation and prevent ferroptotic cell death. Multiple pharmacological strategies have been evaluated to counteract this effect, including direct NRF2 inhibitors such as camptothecin (CPT) and brusatol, preoperative modulators such as metformin and picropodophyllin (PPP), and natural compounds such as tiliroside, bavaquine, and arenobufagin. These interventions often show synergistic activity with sorafenib and other standard treatments, while postoperative effectors such as CYP4F11 and the NRF2-SLC7A11-GPX4 axis have emerged as promising additional intervention points. Despite compelling results in vitro and animal model results, several challenges limit its application to clinical practice. These include the lack of dedicated clinical trials, the limited specificity of available inhibitors, tumor heterogeneity, and potential safety concerns in cirrhotic livers. Future research focuses on the development of selective NRF2 modulators, hepatocyte-targeted approaches such as proteolysis-targeted chimeras (PROTACs) and GalNAc-conjugated oligonucleotides, and biomarker-based patient stratification using genomic, immunohistochemical, and transcriptomic indicators of NRF2 activation. Taken together, contextual NRF2 modulation represents a promising strategy to restore sensitivity to ferroptosis, overcome drug resistance, and improve outcomes in HCC patients.
DOI: https://doi.org/10.37349/emed.2025.1001367
This article belongs to the special issue Lipid Peroxidation and Cancer
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta plaques and tau tangles. Emerging research emphasizes the gut-brain axis as a key modulator of AD pathogenesis, with gut microbiota influencing neuroimmune, neurochemical, and metabolic pathways. This review examines the therapeutic and preventive potential of probiotics, live beneficial microorganisms, in modulating the gut-brain axis to mitigate AD progression. Modifying gut microbiota presents a novel, potentially modifiable approach to influence AD pathophysiology and improve cognitive outcomes, offering insights for adjunctive clinical strategies. A systematic literature search was conducted across PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library for studies published up to July 2025. Studies were classified by design, sample size, follow-up duration, cognitive and biomarker outcomes, and risk of bias, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reproducibility. Preclinical studies indicate that probiotics can regulate gut microbiota, reduce oxidative stress, suppress neuroinflammation, and enhance synaptic plasticity, improving cognition in animal models. Clinical trials suggest potential benefits in humans, including improved memory scores and reduced inflammatory biomarkers, though limited sample sizes, trial duration, and strain variability constrain conclusions. Overall, probiotics demonstrate promise as an adjunctive intervention in AD. Further long-term, strain-specific, and large-scale clinical studies are needed to confirm efficacy, establish causality, and optimize therapeutic strategies.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta plaques and tau tangles. Emerging research emphasizes the gut-brain axis as a key modulator of AD pathogenesis, with gut microbiota influencing neuroimmune, neurochemical, and metabolic pathways. This review examines the therapeutic and preventive potential of probiotics, live beneficial microorganisms, in modulating the gut-brain axis to mitigate AD progression. Modifying gut microbiota presents a novel, potentially modifiable approach to influence AD pathophysiology and improve cognitive outcomes, offering insights for adjunctive clinical strategies. A systematic literature search was conducted across PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library for studies published up to July 2025. Studies were classified by design, sample size, follow-up duration, cognitive and biomarker outcomes, and risk of bias, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reproducibility. Preclinical studies indicate that probiotics can regulate gut microbiota, reduce oxidative stress, suppress neuroinflammation, and enhance synaptic plasticity, improving cognition in animal models. Clinical trials suggest potential benefits in humans, including improved memory scores and reduced inflammatory biomarkers, though limited sample sizes, trial duration, and strain variability constrain conclusions. Overall, probiotics demonstrate promise as an adjunctive intervention in AD. Further long-term, strain-specific, and large-scale clinical studies are needed to confirm efficacy, establish causality, and optimize therapeutic strategies.
DOI: https://doi.org/10.37349/ent.2025.1004120
This article belongs to the special issue Role of Microbiota in Neurological Diseases
Type 2 diabetes mellitus (T2DM), expected to exceed 700 million cases by 2045, is usually attributed to obesity and peripheral resistance but neglects insulin’s structural integrity. This review introduces the Sulfur-Insulin Deformation Hypothesis, positing T2DM as a sulfur metabolism disorder where mitochondrial suffocation disrupts the transsulfuration pathway [methionine to cysteine via cystathionine β-synthase (CBS) and γ-lyase (CGL)], depleting cysteine and glutathione (GSH), impairing protein disulfide isomerase (PDI) activity, and deforming insulin’s disulfide bonds (A6–A11, A7–B7, A20–B19) as a primary trigger of insulin resistance. A literature synthesis was conducted (1995–2025) across PubMed, Scopus, Web of Science, and Google Scholar, using Medical Subject Headings (MeSH) terms like “sulfur metabolism”, “insulin misfolding”, and “mitochondrial dysfunction”. From 1,202 articles, 113 studies were selected, including in vitro insulin folding models, animal metabolic stress data, human sulfur biomarker analyses, and trials of sulfur donors (e.g., N-acetylcysteine). Mitochondrial dysfunction reduces adenosine triphosphate (ATP), depleting cysteine and GSH by 30–73.8% (red blood cell GSH: 1.78 ± 0.28 µmol/g vs. 6.75 ± 0.47 µmol/g Hb, P < 0.001), elevating reactive oxygen species (ROS). This impairs PDI isoforms (PDIA1, PDIA3, PDIA4), disrupting insulin bonds; the A6–A11 bond loses 50–70% affinity [r = –0.65, P < 0.05 for homeostatic model assessment of insulin resistance (HOMA-IR)], hindering phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling and glucose transporter type 4 (GLUT4) translocation. In 225 T2DM patients, PDIA4 elevation correlated with glucose (r = 0.62, P < 0.01) and reduced sensitivity (r = –0.67, P < 0.01). PDIA4 inhibition [presenilin 1 (PS1), IC50 = 4 μM] cuts ROS by 50% (P < 0.01), lowers hemoglobin A1c (HbA1c) by 1.2% (P < 0.05), and boosts β-cell survival by 30% (P < 0.05). Redox-mediated chain splitting degrades 20% of insulin (0.40 nmol/kg/min) at –137 mV, modulated by GSH. The hypothesis redefines T2DM as a sulfur-driven structural disorder, unveiling the gut-mitochondria-sulfur-insulin axis and advocating sulfur-centric therapies (e.g., N-acetylcysteine, methylsulfonylmethane).
Type 2 diabetes mellitus (T2DM), expected to exceed 700 million cases by 2045, is usually attributed to obesity and peripheral resistance but neglects insulin’s structural integrity. This review introduces the Sulfur-Insulin Deformation Hypothesis, positing T2DM as a sulfur metabolism disorder where mitochondrial suffocation disrupts the transsulfuration pathway [methionine to cysteine via cystathionine β-synthase (CBS) and γ-lyase (CGL)], depleting cysteine and glutathione (GSH), impairing protein disulfide isomerase (PDI) activity, and deforming insulin’s disulfide bonds (A6–A11, A7–B7, A20–B19) as a primary trigger of insulin resistance. A literature synthesis was conducted (1995–2025) across PubMed, Scopus, Web of Science, and Google Scholar, using Medical Subject Headings (MeSH) terms like “sulfur metabolism”, “insulin misfolding”, and “mitochondrial dysfunction”. From 1,202 articles, 113 studies were selected, including in vitro insulin folding models, animal metabolic stress data, human sulfur biomarker analyses, and trials of sulfur donors (e.g., N-acetylcysteine). Mitochondrial dysfunction reduces adenosine triphosphate (ATP), depleting cysteine and GSH by 30–73.8% (red blood cell GSH: 1.78 ± 0.28 µmol/g vs. 6.75 ± 0.47 µmol/g Hb, P < 0.001), elevating reactive oxygen species (ROS). This impairs PDI isoforms (PDIA1, PDIA3, PDIA4), disrupting insulin bonds; the A6–A11 bond loses 50–70% affinity [r = –0.65, P < 0.05 for homeostatic model assessment of insulin resistance (HOMA-IR)], hindering phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling and glucose transporter type 4 (GLUT4) translocation. In 225 T2DM patients, PDIA4 elevation correlated with glucose (r = 0.62, P < 0.01) and reduced sensitivity (r = –0.67, P < 0.01). PDIA4 inhibition [presenilin 1 (PS1), IC50 = 4 μM] cuts ROS by 50% (P < 0.01), lowers hemoglobin A1c (HbA1c) by 1.2% (P < 0.05), and boosts β-cell survival by 30% (P < 0.05). Redox-mediated chain splitting degrades 20% of insulin (0.40 nmol/kg/min) at –137 mV, modulated by GSH. The hypothesis redefines T2DM as a sulfur-driven structural disorder, unveiling the gut-mitochondria-sulfur-insulin axis and advocating sulfur-centric therapies (e.g., N-acetylcysteine, methylsulfonylmethane).
DOI: https://doi.org/10.37349/eemd.2025.101444
This article belongs to the special issue Current Views on Pathogenesis, Diagnosis and Management of Type 2 Diabetes Mellitus and Its Complications and Related Conditions
Aim:
Hepatocellular carcinoma (HCC) displays both shared and ethnicity-specific molecular characteristics. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we compared gene expression profiles between Asian and Caucasian HCC patients.
Methods:
Gene expression profiles were analyzed using the PyDESeq2 implementation of DESeq2, applying size factor normalization and dispersion estimation. Differentially expressed genes (DEGs) were identified with thresholds of false discovery rate (FDR) of < 0.05 and |log2FC| ≥ 1.0. Gene annotation, visualization, and pathway enrichment were conducted using Sanbomics, seaborn, and gene set enrichment analysis (GSEA) via the GSEApy package.
Results:
A total of 387 and 250 genes were commonly upregulated and downregulated, respectively, in both populations, including the upregulations of GPC3 and PLVAP and the downregulations of FCN3 and OIT3, indicating their potential as universal HCC markers. Conversely, 16 genes were upregulated in Asians but downregulated in Caucasians, and 25 showed the reverse pattern. Asian-specific upregulation of AKR1B10, UBE2C, and S100P suggests links to viral etiology and immune modulation, while MDK, LCN2, and NQO1 were upregulated in Caucasians, implicating proliferative and metabolic roles. Functional enrichment analysis revealed distinct immune and metabolic pathways. Asians showed elevated ubiquitin ligase activity and suppressed inflammatory responses, while Caucasians exhibited enhanced cytokine signaling, complement activation, and xenobiotic metabolism.
Conclusions:
These findings highlight key molecular differences in HCC across ethnicities and emphasize the value of TCGA data for identifying both shared targets and population-specific therapeutic strategies. Understanding these differences is crucial for advancing precision oncology and developing tailored interventions.
Aim:
Hepatocellular carcinoma (HCC) displays both shared and ethnicity-specific molecular characteristics. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we compared gene expression profiles between Asian and Caucasian HCC patients.
Methods:
Gene expression profiles were analyzed using the PyDESeq2 implementation of DESeq2, applying size factor normalization and dispersion estimation. Differentially expressed genes (DEGs) were identified with thresholds of false discovery rate (FDR) of < 0.05 and |log2FC| ≥ 1.0. Gene annotation, visualization, and pathway enrichment were conducted using Sanbomics, seaborn, and gene set enrichment analysis (GSEA) via the GSEApy package.
Results:
A total of 387 and 250 genes were commonly upregulated and downregulated, respectively, in both populations, including the upregulations of GPC3 and PLVAP and the downregulations of FCN3 and OIT3, indicating their potential as universal HCC markers. Conversely, 16 genes were upregulated in Asians but downregulated in Caucasians, and 25 showed the reverse pattern. Asian-specific upregulation of AKR1B10, UBE2C, and S100P suggests links to viral etiology and immune modulation, while MDK, LCN2, and NQO1 were upregulated in Caucasians, implicating proliferative and metabolic roles. Functional enrichment analysis revealed distinct immune and metabolic pathways. Asians showed elevated ubiquitin ligase activity and suppressed inflammatory responses, while Caucasians exhibited enhanced cytokine signaling, complement activation, and xenobiotic metabolism.
Conclusions:
These findings highlight key molecular differences in HCC across ethnicities and emphasize the value of TCGA data for identifying both shared targets and population-specific therapeutic strategies. Understanding these differences is crucial for advancing precision oncology and developing tailored interventions.
DOI: https://doi.org/10.37349/etat.2025.1002344
Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. Among the most advanced pharmacologic candidates are resmetirom, a highly liver-selective thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) already approved for diabetes and obesity. Although both agents improve hepatic steatosis, their mechanisms of action, extra-hepatic benefits, and safety signatures diverge markedly. Resmetirom, which was approved by the Food and Drug Administration (FDA) in March 2024, acts hepatocentrically to accelerate β-oxidation, lower atherogenic lipoproteins, and deliver early signals necessary for fibrosis regression, all while largely avoiding systemic thyrotoxic effects. Semaglutide acts systemically by reducing caloric load through pronounced weight loss and glycemic control, producing the highest rates of histologic MASH resolution reported to date, albeit with less direct antifibrotic efficacy and characteristic gastrointestinal tolerability issues. This comparative perspective juxtaposes the two compounds with respect to molecular pharmacology, clinical efficacy, safety, and potential clinical positioning, and proposes that, because resmetirom primarily targets hepatic lipid disposal whereas semaglutide unloads systemic caloric pressure, their complementary actions could be harnessed sequentially or in combination to achieve broader, more durable disease modification across the heterogeneous spectrum of patients with MASH.
Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. Among the most advanced pharmacologic candidates are resmetirom, a highly liver-selective thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) already approved for diabetes and obesity. Although both agents improve hepatic steatosis, their mechanisms of action, extra-hepatic benefits, and safety signatures diverge markedly. Resmetirom, which was approved by the Food and Drug Administration (FDA) in March 2024, acts hepatocentrically to accelerate β-oxidation, lower atherogenic lipoproteins, and deliver early signals necessary for fibrosis regression, all while largely avoiding systemic thyrotoxic effects. Semaglutide acts systemically by reducing caloric load through pronounced weight loss and glycemic control, producing the highest rates of histologic MASH resolution reported to date, albeit with less direct antifibrotic efficacy and characteristic gastrointestinal tolerability issues. This comparative perspective juxtaposes the two compounds with respect to molecular pharmacology, clinical efficacy, safety, and potential clinical positioning, and proposes that, because resmetirom primarily targets hepatic lipid disposal whereas semaglutide unloads systemic caloric pressure, their complementary actions could be harnessed sequentially or in combination to achieve broader, more durable disease modification across the heterogeneous spectrum of patients with MASH.
DOI: https://doi.org/10.37349/eds.2025.1008132
This article belongs to the special issue Innovative Therapeutics in Hepato-Gastroenterology
Parkinson’s disease (PD) is a devastating neurodegenerative condition characterized primarily by the degeneration of the dopaminergic neurons in the substantia nigra, causing motor dysfunction and many non-motor symptoms. Available pharmacological treatments and therapies provide symptomatic relief but do not halt the progression of PD. Gene therapy has been recognized as a valuable therapeutic frontier, providing the possibility of disease modification by targeting the underlying molecular and cellular mechanisms of PD. The parts of the methodology used for gene therapy entail the delivery of genetic material into particular regions of the brain with the aid of viral vectors to improve the synthesis of dopamine, maintain the integrity of neurons, or control pathological pathways. Recent clinical trials have shown promising efficacy and safety profiles for many gene therapy methods, consisting of those targeting enzymes in the biosynthesis of dopamine [e.g., L-amino acid decarboxylase (AADC)], synuclein alpha pathology, and neurotrophic factors [e.g., growth-derived neurotrophic factor (GDNF)]. However, in spite of these developments, there are limitations in vector delivery and prolonged expression of genes, as well as patient-specific responses. This review highlights the present landscape of gene therapy in PD, discussing the latest successes, ongoing clinical trials, and future perspectives that could shape therapeutic paradigms for PD.
Parkinson’s disease (PD) is a devastating neurodegenerative condition characterized primarily by the degeneration of the dopaminergic neurons in the substantia nigra, causing motor dysfunction and many non-motor symptoms. Available pharmacological treatments and therapies provide symptomatic relief but do not halt the progression of PD. Gene therapy has been recognized as a valuable therapeutic frontier, providing the possibility of disease modification by targeting the underlying molecular and cellular mechanisms of PD. The parts of the methodology used for gene therapy entail the delivery of genetic material into particular regions of the brain with the aid of viral vectors to improve the synthesis of dopamine, maintain the integrity of neurons, or control pathological pathways. Recent clinical trials have shown promising efficacy and safety profiles for many gene therapy methods, consisting of those targeting enzymes in the biosynthesis of dopamine [e.g., L-amino acid decarboxylase (AADC)], synuclein alpha pathology, and neurotrophic factors [e.g., growth-derived neurotrophic factor (GDNF)]. However, in spite of these developments, there are limitations in vector delivery and prolonged expression of genes, as well as patient-specific responses. This review highlights the present landscape of gene therapy in PD, discussing the latest successes, ongoing clinical trials, and future perspectives that could shape therapeutic paradigms for PD.
DOI: https://doi.org/10.37349/ent.2025.1004119
This article belongs to the special issue Parkinson's Disease: Principal Targets and Interventional Mechanisms
Aim:
To evaluate the precision of computer-assisted surgery simulation in mandibular condyle reconstruction using a costochondral graft.
Methods:
Ten patients (mean age: 14.5 years) with temporomandibular joint (TMJ) pathology and associated pain were included in the study. All patients underwent TMJ reconstruction using costochondral grafts planned through computer-assisted surgical simulation. Preoperative assessment included mouth opening, facial asymmetry, and the differences between planned and actual mandibular positioning.
Results:
Postoperative mouth opening was significantly improved in all patients, and facial profile modifications were enhanced. The site of the costochondral graft relative to the glenoid fossa was found to be satisfactory in postoperative radiographs, computed tomography images, and quantitative analysis.
Conclusions:
The results of this study demonstrate that virtual surgical planning combined with 3D-printed guiding templates enhanced treatment planning, provided precise osteotomy guidance, facilitated accurate repositioning of bony segments, and improved the contouring of mandibular anatomy in the management of TMJ deformities (ClinicalTrials.gov identifier: NCT06811415).
Aim:
To evaluate the precision of computer-assisted surgery simulation in mandibular condyle reconstruction using a costochondral graft.
Methods:
Ten patients (mean age: 14.5 years) with temporomandibular joint (TMJ) pathology and associated pain were included in the study. All patients underwent TMJ reconstruction using costochondral grafts planned through computer-assisted surgical simulation. Preoperative assessment included mouth opening, facial asymmetry, and the differences between planned and actual mandibular positioning.
Results:
Postoperative mouth opening was significantly improved in all patients, and facial profile modifications were enhanced. The site of the costochondral graft relative to the glenoid fossa was found to be satisfactory in postoperative radiographs, computed tomography images, and quantitative analysis.
Conclusions:
The results of this study demonstrate that virtual surgical planning combined with 3D-printed guiding templates enhanced treatment planning, provided precise osteotomy guidance, facilitated accurate repositioning of bony segments, and improved the contouring of mandibular anatomy in the management of TMJ deformities (ClinicalTrials.gov identifier: NCT06811415).
DOI: https://doi.org/10.37349/ebmx.2025.101350
Aim:
Obsessive-compulsive disorder (OCD) is a mental health condition that significantly interferes with the school environment. The concealment of symptoms, lack of identification, and limited knowledge about the disorder often lead to delays in help-seeking, which are associated with greater chronicity, increased interference, and poorer treatment response. Programmes that educate teachers on early detection of OCD could help identify children at risk and promote help-seeking behavior. This study analyzed the feasibility, acceptability, and preliminary efficacy of the health app esTOCma from both quantitative and qualitative perspectives among teachers, as well as explored areas for improvement.
Methods:
A total of 19 teachers (mean age = 47.74 years, SD = 11.2) completed the intervention along with pre- and post-intervention assessments through the app. In addition, they responded to open-ended questions to share their opinions about the app.
Results:
Teachers took an average of 4.89 days (SD = 4.21) to complete the intervention. The app demonstrated excellent usability (M = 85.5, SD = 10.3) and was found useful by the majority of participants (89.5%), who reported satisfaction (84.2%) and stated they had learned considerably (73.7%) through its use. Upon completing the intervention, participants showed greater understanding of OCD and its treatments (MHLQ-R: z = –2.92, p = 0.004), lower levels of stigma (AQ-9: z = –3.67, p < 0.001), and a higher intention to seek professional help in case of experiencing obsessive-compulsive symptoms (GHSQ: z = –2.50, p = 0.012).
Conclusions:
esTOCma appears to be a feasible app in an educational context, showing high acceptability among participating teachers. Moreover, the app increases knowledge and understanding of OCD, promotes the intention to seek professional help, and reduces stigma toward the disorder. Several improvements are suggested to further enhance the app’s potential impact in educational settings.
Aim:
Obsessive-compulsive disorder (OCD) is a mental health condition that significantly interferes with the school environment. The concealment of symptoms, lack of identification, and limited knowledge about the disorder often lead to delays in help-seeking, which are associated with greater chronicity, increased interference, and poorer treatment response. Programmes that educate teachers on early detection of OCD could help identify children at risk and promote help-seeking behavior. This study analyzed the feasibility, acceptability, and preliminary efficacy of the health app esTOCma from both quantitative and qualitative perspectives among teachers, as well as explored areas for improvement.
Methods:
A total of 19 teachers (mean age = 47.74 years, SD = 11.2) completed the intervention along with pre- and post-intervention assessments through the app. In addition, they responded to open-ended questions to share their opinions about the app.
Results:
Teachers took an average of 4.89 days (SD = 4.21) to complete the intervention. The app demonstrated excellent usability (M = 85.5, SD = 10.3) and was found useful by the majority of participants (89.5%), who reported satisfaction (84.2%) and stated they had learned considerably (73.7%) through its use. Upon completing the intervention, participants showed greater understanding of OCD and its treatments (MHLQ-R: z = –2.92, p = 0.004), lower levels of stigma (AQ-9: z = –3.67, p < 0.001), and a higher intention to seek professional help in case of experiencing obsessive-compulsive symptoms (GHSQ: z = –2.50, p = 0.012).
Conclusions:
esTOCma appears to be a feasible app in an educational context, showing high acceptability among participating teachers. Moreover, the app increases knowledge and understanding of OCD, promotes the intention to seek professional help, and reduces stigma toward the disorder. Several improvements are suggested to further enhance the app’s potential impact in educational settings.
DOI: https://doi.org/10.37349/edht.2025.101169
This article belongs to the special issue Digital Health Innovations in the Battle Against Psychological Problems: Progress, Hurdles, and Prospects
Aim:
Olea europaea, an endemic plant of the Mediterranean basin, exhibits a flowering period from April to June, requiring high temperatures and sensitivity to low humidity, rainfall, and windiness. Allergy to O. europaea affects 13.85% of the Southern Italian population. This study investigated O. europaea pollen concentration, morphological and biochemical variations, and clinical symptoms over a 6-year period (2017–2022).
Methods:
Pollen concentration in Southern Italy (Apulia, Bari) was analyzed alongside weather variables (temperature, precipitation, humidity, and windiness) using existing databases (Arpa Puglia; time and date). Optical and fluorescence microscopy techniques were employed to assess pollen morphology and biochemical characteristics. Additionally, the absolute number of prescriptions for various antihistamine drugs (cetirizine, ebastine, bilastine, desloratadine, rupatadine, levocetirizine, fexofenadine, loratadine) was calculated.
Results:
The lowest pollen count occurred in the 2018 (91.1 pollen per m3/week), while the highest was recorded in the 2021 (2,545.3 pollen per m3/week). In 2019, the pollen peak was delayed by 2 weeks. Notably, 2018 exhibited more rainy days in May and June and higher humidity percentages (April 73%, May 70%, June 72%). In contrast, 2021 had lower humidity values (April 68%, May 61%, June 59%) and fewer rainy days (1 day in May and none in June). No changes in pollen size were observed, but modifications in O. europaea pollen fuchsin fluorescence were noted in 2018 and 2021. The number of drug prescriptions was highest in 2021.
Conclusions:
This study highlights that the flowering period, morphology, and pollen production of O. europaea may influence patient symptomatology and the need for antihistamine medications.
Aim:
Olea europaea, an endemic plant of the Mediterranean basin, exhibits a flowering period from April to June, requiring high temperatures and sensitivity to low humidity, rainfall, and windiness. Allergy to O. europaea affects 13.85% of the Southern Italian population. This study investigated O. europaea pollen concentration, morphological and biochemical variations, and clinical symptoms over a 6-year period (2017–2022).
Methods:
Pollen concentration in Southern Italy (Apulia, Bari) was analyzed alongside weather variables (temperature, precipitation, humidity, and windiness) using existing databases (Arpa Puglia; time and date). Optical and fluorescence microscopy techniques were employed to assess pollen morphology and biochemical characteristics. Additionally, the absolute number of prescriptions for various antihistamine drugs (cetirizine, ebastine, bilastine, desloratadine, rupatadine, levocetirizine, fexofenadine, loratadine) was calculated.
Results:
The lowest pollen count occurred in the 2018 (91.1 pollen per m3/week), while the highest was recorded in the 2021 (2,545.3 pollen per m3/week). In 2019, the pollen peak was delayed by 2 weeks. Notably, 2018 exhibited more rainy days in May and June and higher humidity percentages (April 73%, May 70%, June 72%). In contrast, 2021 had lower humidity values (April 68%, May 61%, June 59%) and fewer rainy days (1 day in May and none in June). No changes in pollen size were observed, but modifications in O. europaea pollen fuchsin fluorescence were noted in 2018 and 2021. The number of drug prescriptions was highest in 2021.
Conclusions:
This study highlights that the flowering period, morphology, and pollen production of O. europaea may influence patient symptomatology and the need for antihistamine medications.
DOI: https://doi.org/10.37349/eaa.2025.100996
This article belongs to the special issue Climate Change, Allergy, and Immunotherapy
Background:
Current treatment for medulloblastoma involves craniospinal irradiation (CSI) with a radiation boost to the posterior fossa and adjuvant chemotherapy following surgical resection. Due to neurotoxic effects of CSI—particularly its impact on cognitive function and intelligence quotient (IQ)—recent efforts have focused on reducing CSI dosage. This systematic review compares standard-dose CSI (SDCSI) versus low-dose CSI (LDCSI) in terms of relapse rate, event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
Methods:
A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened studies for eligibility and extracted data on study design, patient demographics, CSI dosage, chemotherapy regimens, EFS, OS, relapse rates, and reported side effects.
Results:
Out of 749 identified studies, 24 met the inclusion criteria for this review. Reported 5-year EFS ranged from 27.3% to 83%, and 5-year OS ranged from 41 ± 8% to 94.7 ± 3.4%. Commonly reported adverse effects included hematologic toxicity, secondary malignancies, disease progression, nausea/vomiting, and cognitive impairment. IQ outcomes ranged from 71 to 98.6, with studies consistently showing that LDCSI was associated with a smaller decline in IQ compared to SDCSI. Factors such as age, molecular subgroup, and histological features were identified as important variables for risk stratification.
Discussion:
LDCSI combined with chemotherapy may provide sufficient treatment efficacy for medulloblastoma while mitigating neurocognitive decline. Future research should focus on optimizing chemotherapy regimens and refining treatment stratification based on molecular and histological subtypes, particularly in standard- versus high-risk patients.
Background:
Current treatment for medulloblastoma involves craniospinal irradiation (CSI) with a radiation boost to the posterior fossa and adjuvant chemotherapy following surgical resection. Due to neurotoxic effects of CSI—particularly its impact on cognitive function and intelligence quotient (IQ)—recent efforts have focused on reducing CSI dosage. This systematic review compares standard-dose CSI (SDCSI) versus low-dose CSI (LDCSI) in terms of relapse rate, event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
Methods:
A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened studies for eligibility and extracted data on study design, patient demographics, CSI dosage, chemotherapy regimens, EFS, OS, relapse rates, and reported side effects.
Results:
Out of 749 identified studies, 24 met the inclusion criteria for this review. Reported 5-year EFS ranged from 27.3% to 83%, and 5-year OS ranged from 41 ± 8% to 94.7 ± 3.4%. Commonly reported adverse effects included hematologic toxicity, secondary malignancies, disease progression, nausea/vomiting, and cognitive impairment. IQ outcomes ranged from 71 to 98.6, with studies consistently showing that LDCSI was associated with a smaller decline in IQ compared to SDCSI. Factors such as age, molecular subgroup, and histological features were identified as important variables for risk stratification.
Discussion:
LDCSI combined with chemotherapy may provide sufficient treatment efficacy for medulloblastoma while mitigating neurocognitive decline. Future research should focus on optimizing chemotherapy regimens and refining treatment stratification based on molecular and histological subtypes, particularly in standard- versus high-risk patients.
DOI: https://doi.org/10.37349/emed.2025.1001366
Aim:
This study analyses the time series of daily increases in the number of diagnosed COVID-19 cases in Russia and countries from different continents. The aim of the study is to identify the specifics of the population response of different countries to the spread of the pandemic and anti-epidemic measures of public authorities to determine the most effective model to describe this process. This is a problematic, synoptic, and pilot study.
Methods:
To evaluate this response strategy, models and methods from reliability theory are used to describe the probability of health protection, the probability density function of an increasing number of cases, the integrated risk of infection, the risk of morbidity, the acceptable risk, and the manageability of the epidemic situation. To approximate infection curves, various daily incidence rate functions are used and compared, and their coefficients are calculated for various pandemic waves.
Results:
The results demonstrate that the Fréchet distribution function is the best model for the epidemic process. Indicators of variability in acceptable risk were identified during the first stage of pandemic development, showing the varying controllability of the situation by health systems. Through meta-analysis, country distributions were shown to appear as a single pattern, abstracted from local conditions. Estimated coefficients of reliability functions allow the construction of cartograms that reflect the peculiarities of state epidemic regulation and the stages of global pandemic deployment.
Conclusions:
The findings confirm the effectiveness of the selected model in terms of reliability theory and identify directions for model improvement, taking into account the dynamic nature of the pandemic and its specific characteristics in different countries. The study is based on the methodological approach of function stratification (geometric fiber bundle). It allows for a deeper understanding of the identified patterns within a broader knowledge system.
Aim:
This study analyses the time series of daily increases in the number of diagnosed COVID-19 cases in Russia and countries from different continents. The aim of the study is to identify the specifics of the population response of different countries to the spread of the pandemic and anti-epidemic measures of public authorities to determine the most effective model to describe this process. This is a problematic, synoptic, and pilot study.
Methods:
To evaluate this response strategy, models and methods from reliability theory are used to describe the probability of health protection, the probability density function of an increasing number of cases, the integrated risk of infection, the risk of morbidity, the acceptable risk, and the manageability of the epidemic situation. To approximate infection curves, various daily incidence rate functions are used and compared, and their coefficients are calculated for various pandemic waves.
Results:
The results demonstrate that the Fréchet distribution function is the best model for the epidemic process. Indicators of variability in acceptable risk were identified during the first stage of pandemic development, showing the varying controllability of the situation by health systems. Through meta-analysis, country distributions were shown to appear as a single pattern, abstracted from local conditions. Estimated coefficients of reliability functions allow the construction of cartograms that reflect the peculiarities of state epidemic regulation and the stages of global pandemic deployment.
Conclusions:
The findings confirm the effectiveness of the selected model in terms of reliability theory and identify directions for model improvement, taking into account the dynamic nature of the pandemic and its specific characteristics in different countries. The study is based on the methodological approach of function stratification (geometric fiber bundle). It allows for a deeper understanding of the identified patterns within a broader knowledge system.
DOI: https://doi.org/10.37349/edht.2025.101168
This article belongs to the special issue Data-informed Decision Making in Healthcare
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder in which iron acts as both a metabolic “spark” and an accelerant of liver injury. This integrates emerging evidence that iron-driven oxidative stress and low-grade inflammation are mutually reinforcing processes in metabolic liver disease. In this perspective article, epidemiological evidence, molecular insights, and emerging clinical data are integrated to clarify how hyperferritinemia, often dismissed as a mere inflammatory marker, maps onto genuine iron redistribution and overload in the metabolic liver. Physiological iron homeostasis and its disruption by adiposity-related inflammation, hyperinsulinemia, sex hormones, and common HFE variants, creating a labile catalytic iron pool that fuels Fenton chemistry in lipid-laden hepatocytes. Population studies and expert-panel criteria are summarized that define “metabolic hyperferritinemia” and stratify dysmetabolic iron accumulation into three magnetic resonance imaging (MRI)-based grades, each linked to stepwise increases in steatosis, fibrosis, and clinical events. Mechanistically, excess Fe2+ triggers lipid peroxidation, mitochondrial dysfunction, ferroptosis, Kupffer cell activation, endoplasmic reticulum stress, and hepatic stellate cell sensitization to TGF-β, thereby accelerating the transition from steatosis to steatohepatitis and fibrosis. Finally, the diagnostic algorithms, iron-modulating therapies (phlebotomy, hepcidin agonists, diet), and prospective data supporting ferritin-based triage in clinics are discussed. Collectively, the outlined evidence positions iron not only as a biomarker but also as a modifiable driver of MASLD progression, underscoring the need for randomized trials that test whether targeted iron reduction improves hard hepatic outcomes.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder in which iron acts as both a metabolic “spark” and an accelerant of liver injury. This integrates emerging evidence that iron-driven oxidative stress and low-grade inflammation are mutually reinforcing processes in metabolic liver disease. In this perspective article, epidemiological evidence, molecular insights, and emerging clinical data are integrated to clarify how hyperferritinemia, often dismissed as a mere inflammatory marker, maps onto genuine iron redistribution and overload in the metabolic liver. Physiological iron homeostasis and its disruption by adiposity-related inflammation, hyperinsulinemia, sex hormones, and common HFE variants, creating a labile catalytic iron pool that fuels Fenton chemistry in lipid-laden hepatocytes. Population studies and expert-panel criteria are summarized that define “metabolic hyperferritinemia” and stratify dysmetabolic iron accumulation into three magnetic resonance imaging (MRI)-based grades, each linked to stepwise increases in steatosis, fibrosis, and clinical events. Mechanistically, excess Fe2+ triggers lipid peroxidation, mitochondrial dysfunction, ferroptosis, Kupffer cell activation, endoplasmic reticulum stress, and hepatic stellate cell sensitization to TGF-β, thereby accelerating the transition from steatosis to steatohepatitis and fibrosis. Finally, the diagnostic algorithms, iron-modulating therapies (phlebotomy, hepcidin agonists, diet), and prospective data supporting ferritin-based triage in clinics are discussed. Collectively, the outlined evidence positions iron not only as a biomarker but also as a modifiable driver of MASLD progression, underscoring the need for randomized trials that test whether targeted iron reduction improves hard hepatic outcomes.
DOI: https://doi.org/10.37349/edd.2025.100599
This article belongs to the special issue Advances in Hepato-gastroenterology: Diagnosis, Prognostication, and Disease Stratification
Aim:
TNF-related apoptosis-inducing ligand (TRAIL) is a promising targeted anti-cancer agent for several types of cancer, including non-small cell lung cancer (NSCLC). The proteasome inhibitor bortezomib can further potentiate rhTRAIL-induced apoptosis in NSCLC cells. Here, the mechanisms underlying this sensitization were examined in TRAIL-sensitive H460 and TRAIL-resistant A549 and SW1573 NSCLC cells.
Methods:
NSCLC cell lines were treated with rhTRAIL and bortezomib, and apoptosis was assessed through caspase activation assays, western blotting, and gene silencing of key apoptotic regulators, including Bid, XIAP, and cFLIP. Clonogenic assays were performed to evaluate long-term tumor growth suppression.
Results:
Bortezomib sensitization mechanisms varied across NSCLC cell lines. Combined rhTRAIL/bortezomib treatment enhanced apoptosis across all cell lines. In TRAIL-sensitive H460 cells, rapid caspase activation was observed, with both extrinsic and intrinsic apoptotic pathways contributing to cell death. Sensitization in H460 cells was predominantly mediated via the caspase-8/Bid amplification loop. In A549 cells, the bortezomib sensitizing effect also relied on the caspase-8/Bid amplification loop. Additionally, the inhibition of Bid and XIAP emphasized the critical role of mitochondrial pathways in apoptosis. In SW1573 cells, limited caspase cleavage was detected, with distinct cleavage patterns suggesting cell-specific apoptotic mechanisms. In this cell line, bortezomib primarily enhanced the extrinsic apoptotic pathway, with XIAP depression further increasing apoptosis. Silencing cFLIP, a caspase-8 inhibitor, significantly improved rhTRAIL sensitivity, emphasizing the critical role of caspase-8 activation in overcoming resistance in SW1573. The clonogenic assay demonstrated that bortezomib combined with rhTRAIL significantly suppressed tumor growth, especially in resistant cell lines.
Conclusions:
This study underscores bortezomib’s ability to differentially enhance rhTRAIL-induced apoptosis by targeting multiple apoptotic regulators. The variety of effects that bortezomib can exert to enhance rhTRAIL-induced apoptosis makes it a very powerful combination for the treatment of NSCLC and various other types of cancer cells.
Aim:
TNF-related apoptosis-inducing ligand (TRAIL) is a promising targeted anti-cancer agent for several types of cancer, including non-small cell lung cancer (NSCLC). The proteasome inhibitor bortezomib can further potentiate rhTRAIL-induced apoptosis in NSCLC cells. Here, the mechanisms underlying this sensitization were examined in TRAIL-sensitive H460 and TRAIL-resistant A549 and SW1573 NSCLC cells.
Methods:
NSCLC cell lines were treated with rhTRAIL and bortezomib, and apoptosis was assessed through caspase activation assays, western blotting, and gene silencing of key apoptotic regulators, including Bid, XIAP, and cFLIP. Clonogenic assays were performed to evaluate long-term tumor growth suppression.
Results:
Bortezomib sensitization mechanisms varied across NSCLC cell lines. Combined rhTRAIL/bortezomib treatment enhanced apoptosis across all cell lines. In TRAIL-sensitive H460 cells, rapid caspase activation was observed, with both extrinsic and intrinsic apoptotic pathways contributing to cell death. Sensitization in H460 cells was predominantly mediated via the caspase-8/Bid amplification loop. In A549 cells, the bortezomib sensitizing effect also relied on the caspase-8/Bid amplification loop. Additionally, the inhibition of Bid and XIAP emphasized the critical role of mitochondrial pathways in apoptosis. In SW1573 cells, limited caspase cleavage was detected, with distinct cleavage patterns suggesting cell-specific apoptotic mechanisms. In this cell line, bortezomib primarily enhanced the extrinsic apoptotic pathway, with XIAP depression further increasing apoptosis. Silencing cFLIP, a caspase-8 inhibitor, significantly improved rhTRAIL sensitivity, emphasizing the critical role of caspase-8 activation in overcoming resistance in SW1573. The clonogenic assay demonstrated that bortezomib combined with rhTRAIL significantly suppressed tumor growth, especially in resistant cell lines.
Conclusions:
This study underscores bortezomib’s ability to differentially enhance rhTRAIL-induced apoptosis by targeting multiple apoptotic regulators. The variety of effects that bortezomib can exert to enhance rhTRAIL-induced apoptosis makes it a very powerful combination for the treatment of NSCLC and various other types of cancer cells.
DOI: https://doi.org/10.37349/etat.2025.1002342
DOI: https://doi.org/10.37349/etat.2025.1002343
Guillain-Barré Syndrome (GBS) is a rare cause of acute, flaccid paralysis and affects populations around the world, usually in the setting of recent gastrointestinal infection. The myelin sheaths of affected patients are destroyed, and consequently, the disease can manifest variably with the most common complaints including weakness, disturbances in sensation, and pain. Multiple available pharmacotherapies are employed to address disease progression and promote the reversal of symptoms. However, there is no widely accepted guideline detailing tiers of pain management options, despite pain being a significant primary complaint during the acute phase of the disease. To address this, we searched the GBS literature for publications that specifically discussed patient pain, how the pain was managed by the clinician, and how patients responded to various modalities. We discuss the findings of the literature review we conducted, evaluate the expansive list of existing options for treating pain and how they fared in symptom resolution, and draw conclusions based on our observations of which interventions addressed patient pain effectively and which were less successful. While general management of GBS, including treatment and efforts towards symptom reversal, has been robustly discussed in the literature, our work stresses the lack of research towards pain management in GBS and emphasizes the need to fill the gap in patient care for patients with this disease.
Guillain-Barré Syndrome (GBS) is a rare cause of acute, flaccid paralysis and affects populations around the world, usually in the setting of recent gastrointestinal infection. The myelin sheaths of affected patients are destroyed, and consequently, the disease can manifest variably with the most common complaints including weakness, disturbances in sensation, and pain. Multiple available pharmacotherapies are employed to address disease progression and promote the reversal of symptoms. However, there is no widely accepted guideline detailing tiers of pain management options, despite pain being a significant primary complaint during the acute phase of the disease. To address this, we searched the GBS literature for publications that specifically discussed patient pain, how the pain was managed by the clinician, and how patients responded to various modalities. We discuss the findings of the literature review we conducted, evaluate the expansive list of existing options for treating pain and how they fared in symptom resolution, and draw conclusions based on our observations of which interventions addressed patient pain effectively and which were less successful. While general management of GBS, including treatment and efforts towards symptom reversal, has been robustly discussed in the literature, our work stresses the lack of research towards pain management in GBS and emphasizes the need to fill the gap in patient care for patients with this disease.
DOI: https://doi.org/10.37349/en.2025.1006114
Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered.
Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered.
DOI: https://doi.org/10.37349/ei.2025.1003224
This article belongs to the special issue The Role of Immune Checkpoint Molecules in Cancer and Hematological Malignancies
Cutaneous lupus erythematosus (CLE) is the most common organ manifestation in individuals diagnosed with systemic lupus erythematosus (SLE). CLE can occur either alone or in association with SLE; in the latter case, it substantially increases the occurrence of disease flares and can cause disfigurement. The clinical pathogenesis of CLE is well established, as exposure to ultraviolet (UV) light and/or other environmental triggers, such as smoking or drug use, can lead to keratinocyte death in genetically susceptible individuals. This in turn activates cytotoxic T cells, plasmacytoid dendritic cells (pDCs), and B cells, creating a continuous interaction between the innate and adaptive immune systems. This interaction plays a pivotal role in CLE development, driving the formation of skin lesions. However, the molecular mechanisms underlying these cutaneous manifestations are not yet fully understood. While significant advances have been made in SLE treatment over the past few decades, U.S. Food and Drug Administration (FDA)-approved therapies remain limited to hydroxychloroquine, glucocorticoids, belimumab, and anifrolumab. Although new therapies for CLE have emerged, given the highly heterogeneous nature of the condition, personalized medicine is essential to prevent disfigurement and systemic disease flares. Understanding the molecular pathogenesis of CLE is crucial for developing targeted therapies and improving patient outcomes. This review presents current insights into CLE pathogenesis, highlighting key mechanisms driving the disease and exploring recent advances in treatments that have shown promise in clinical practice.
Cutaneous lupus erythematosus (CLE) is the most common organ manifestation in individuals diagnosed with systemic lupus erythematosus (SLE). CLE can occur either alone or in association with SLE; in the latter case, it substantially increases the occurrence of disease flares and can cause disfigurement. The clinical pathogenesis of CLE is well established, as exposure to ultraviolet (UV) light and/or other environmental triggers, such as smoking or drug use, can lead to keratinocyte death in genetically susceptible individuals. This in turn activates cytotoxic T cells, plasmacytoid dendritic cells (pDCs), and B cells, creating a continuous interaction between the innate and adaptive immune systems. This interaction plays a pivotal role in CLE development, driving the formation of skin lesions. However, the molecular mechanisms underlying these cutaneous manifestations are not yet fully understood. While significant advances have been made in SLE treatment over the past few decades, U.S. Food and Drug Administration (FDA)-approved therapies remain limited to hydroxychloroquine, glucocorticoids, belimumab, and anifrolumab. Although new therapies for CLE have emerged, given the highly heterogeneous nature of the condition, personalized medicine is essential to prevent disfigurement and systemic disease flares. Understanding the molecular pathogenesis of CLE is crucial for developing targeted therapies and improving patient outcomes. This review presents current insights into CLE pathogenesis, highlighting key mechanisms driving the disease and exploring recent advances in treatments that have shown promise in clinical practice.
DOI: https://doi.org/10.37349/ei.2025.1003222
The human vaginal microbiome plays a pivotal role in maintaining female reproductive health through its Lactobacillus-dominated microbial ecology. These bacteria contribute to the acidic pH of the vagina by producing lactic acid, ultimately preventing the colonization of pathogens. Additionally, they produce bacteriocins and hydrogen peroxide, which are detrimental to other microorganisms. Human vaginal microbiota is subjected to alterations with advancement in age, hormonal status, puberty, menstruation cycle, pregnancy and gestation, vaginal tract diseases, exposure to antibiotics, etc. Diet, lifestyle factors, obesity, and gestational diabetes are also reported to cause a shift in vaginal microbiota. This review thoroughly illustrates the perpetually changing dynamics of vaginal microbiota throughout women’s lives, as well as focuses on the impact of dysbiosis in bacterial vaginosis. More emphasis is given on immunological changes observed during bacterial vaginosis, mainly IL-1β, and its involvement in the development of preeclampsia. Thereby, this review highlights a mechanistic link between lower genital tract disease, bacterial vaginosis, and a hypertensive disorder of pregnancy, preeclampsia, via IL-1β–ROR-γt–Th17 axis, which is regulated by vitamin D, with a suggestion on how shifts in vaginal microbial community may pose a risk for preeclampsia.
The human vaginal microbiome plays a pivotal role in maintaining female reproductive health through its Lactobacillus-dominated microbial ecology. These bacteria contribute to the acidic pH of the vagina by producing lactic acid, ultimately preventing the colonization of pathogens. Additionally, they produce bacteriocins and hydrogen peroxide, which are detrimental to other microorganisms. Human vaginal microbiota is subjected to alterations with advancement in age, hormonal status, puberty, menstruation cycle, pregnancy and gestation, vaginal tract diseases, exposure to antibiotics, etc. Diet, lifestyle factors, obesity, and gestational diabetes are also reported to cause a shift in vaginal microbiota. This review thoroughly illustrates the perpetually changing dynamics of vaginal microbiota throughout women’s lives, as well as focuses on the impact of dysbiosis in bacterial vaginosis. More emphasis is given on immunological changes observed during bacterial vaginosis, mainly IL-1β, and its involvement in the development of preeclampsia. Thereby, this review highlights a mechanistic link between lower genital tract disease, bacterial vaginosis, and a hypertensive disorder of pregnancy, preeclampsia, via IL-1β–ROR-γt–Th17 axis, which is regulated by vitamin D, with a suggestion on how shifts in vaginal microbial community may pose a risk for preeclampsia.
DOI: https://doi.org/10.37349/ei.2025.1003223
The green synthesis of silver nanoparticles (AgNPs) has recently gained prominence as a sustainable and eco-friendly alternative to conventional physical and chemical methods. Utilizing biological entities such as plant extracts, bacteria, fungi, and biomolecules, the method acts by both reducing and stabilizing mechanisms. It does not use any harmful chemical substances, thus proving to be eco-friendly. Green-synthesized AgNPs exhibit enhanced biocompatibility, stability, and targeted delivery of the drug due to the use of naturally derived surface capping agents. These unique characteristics allow selective interference with cancer cells. The mechanism involved is the generation of reactive oxygen species (ROS), the induction of apoptosis, DNA damage, and cell cycle arrest. Green AgNPs also possess broad-spectrum antimicrobial, catalytic, antiparasitic, and anti-inflammatory properties, supporting the fact that they can be utilised in biomedical fields such as drug delivery, bioimaging, biosensing, tissue engineering, and regenerative medicine. Recent advancements have focused on controlling NP size, shape, and surface functionality to maximize efficacy while simultaneously minimizing cytotoxicity. This review provides a comprehensive analysis of the latest green synthesis strategies, their characterizations, and the molecular mechanisms by which they exert anticancer effects. Recent patents highlight the clinical potential of AgNPs in cancer therapy. US Patent 12201650 (2025) describes green synthesis using Caralluma sinaica, while other patents (WO2007001453, US7462753) outline adaptable biomedical formulations. Studies on biogenic AgNPs also show significant tumor inhibition and selective cytotoxicity against cancer cells. Furthermore, the article discusses current biomedical applications and critically evaluates the limitations, such as reproducibility, toxicity concerns, and scalability for clinical translation. Addressing these challenges is essential for the integration of green AgNPs into mainstream cancer therapeutics. The convergence of nanotechnology and biologically derived synthesis opens promising avenues for the development of safe, effective, and environmentally sustainable medical innovations.
The green synthesis of silver nanoparticles (AgNPs) has recently gained prominence as a sustainable and eco-friendly alternative to conventional physical and chemical methods. Utilizing biological entities such as plant extracts, bacteria, fungi, and biomolecules, the method acts by both reducing and stabilizing mechanisms. It does not use any harmful chemical substances, thus proving to be eco-friendly. Green-synthesized AgNPs exhibit enhanced biocompatibility, stability, and targeted delivery of the drug due to the use of naturally derived surface capping agents. These unique characteristics allow selective interference with cancer cells. The mechanism involved is the generation of reactive oxygen species (ROS), the induction of apoptosis, DNA damage, and cell cycle arrest. Green AgNPs also possess broad-spectrum antimicrobial, catalytic, antiparasitic, and anti-inflammatory properties, supporting the fact that they can be utilised in biomedical fields such as drug delivery, bioimaging, biosensing, tissue engineering, and regenerative medicine. Recent advancements have focused on controlling NP size, shape, and surface functionality to maximize efficacy while simultaneously minimizing cytotoxicity. This review provides a comprehensive analysis of the latest green synthesis strategies, their characterizations, and the molecular mechanisms by which they exert anticancer effects. Recent patents highlight the clinical potential of AgNPs in cancer therapy. US Patent 12201650 (2025) describes green synthesis using Caralluma sinaica, while other patents (WO2007001453, US7462753) outline adaptable biomedical formulations. Studies on biogenic AgNPs also show significant tumor inhibition and selective cytotoxicity against cancer cells. Furthermore, the article discusses current biomedical applications and critically evaluates the limitations, such as reproducibility, toxicity concerns, and scalability for clinical translation. Addressing these challenges is essential for the integration of green AgNPs into mainstream cancer therapeutics. The convergence of nanotechnology and biologically derived synthesis opens promising avenues for the development of safe, effective, and environmentally sustainable medical innovations.
DOI: https://doi.org/10.37349/etat.2025.1002341
This article belongs to the special issue Potential Clinical Applications of Inorganic Nanomaterials in Cancer
