Previous
Aim:
Intravesical Bacillus Calmette–Guérin (BCG) is the standard therapy for non-muscle invasive bladder cancer (NMIBC); however, many patients experience recurrence or progression. We examined how urinary immune signals and the urinary microbiome change across BCG and are related to outcomes.
Methods:
In this single-center prospective cohort study, adults with NMIBC underwent transurethral resection of bladder tumor (TURBT), followed by BCG induction. Urine was collected before TURBT, before BCG, after BCG induction, and three months later. Urine sediment mRNA (PD-L1, PD-L2, CD33, and CD204) was quantified using TaqMan ΔCt. The urinary microbiome was profiled using 16S rRNA gene sequencing, and diversity, composition, and taxon balance were evaluated using nonparametric tests, PERMANOVA, repeated-measures correlations, and mixed-effects models. We analyzed the relationship between the urinary microbiome and prognosis.
Results:
Twenty-three patients were analyzed; ten recurrences, eight progressions, and three deaths were observed. Relative to baseline, CD33 increased after BCG and after three months; PD-L2 increased immediately after BCG and returned to baseline by three months; PD-L1 and CD204 increased after BCG. Shannon alpha-diversity was unchanged, but total read count was higher at three months, with stable beta-diversity and dispersion. Higher PD-L1 expression was associated with lower Actinobacteria abundance in the bladder cancer microenvironment. A higher post-BCG Firmicutes/Bacteroidetes ratio was associated with worse prognosis, with the clearest signal for progression-free survival (PFS) observed in the univariate Cox models. Higher post-BCG Corynebacterium and Enterobacteriaceae abundance was associated with better PFS.
Conclusions:
BCG was associated with higher urinary PD-L1/PD-L2 and myeloid marker transcripts, while overall community structure remained stable. These exploratory data support that pre-BCG microbial features may be related to early response, and post-BCG profiles may reflect durability and survival. Urine immune-microbiome profiling could be a feasible, noninvasive adjunct for monitoring and risk stratification in NMIBC.
Aim:
Intravesical Bacillus Calmette–Guérin (BCG) is the standard therapy for non-muscle invasive bladder cancer (NMIBC); however, many patients experience recurrence or progression. We examined how urinary immune signals and the urinary microbiome change across BCG and are related to outcomes.
Methods:
In this single-center prospective cohort study, adults with NMIBC underwent transurethral resection of bladder tumor (TURBT), followed by BCG induction. Urine was collected before TURBT, before BCG, after BCG induction, and three months later. Urine sediment mRNA (PD-L1, PD-L2, CD33, and CD204) was quantified using TaqMan ΔCt. The urinary microbiome was profiled using 16S rRNA gene sequencing, and diversity, composition, and taxon balance were evaluated using nonparametric tests, PERMANOVA, repeated-measures correlations, and mixed-effects models. We analyzed the relationship between the urinary microbiome and prognosis.
Results:
Twenty-three patients were analyzed; ten recurrences, eight progressions, and three deaths were observed. Relative to baseline, CD33 increased after BCG and after three months; PD-L2 increased immediately after BCG and returned to baseline by three months; PD-L1 and CD204 increased after BCG. Shannon alpha-diversity was unchanged, but total read count was higher at three months, with stable beta-diversity and dispersion. Higher PD-L1 expression was associated with lower Actinobacteria abundance in the bladder cancer microenvironment. A higher post-BCG Firmicutes/Bacteroidetes ratio was associated with worse prognosis, with the clearest signal for progression-free survival (PFS) observed in the univariate Cox models. Higher post-BCG Corynebacterium and Enterobacteriaceae abundance was associated with better PFS.
Conclusions:
BCG was associated with higher urinary PD-L1/PD-L2 and myeloid marker transcripts, while overall community structure remained stable. These exploratory data support that pre-BCG microbial features may be related to early response, and post-BCG profiles may reflect durability and survival. Urine immune-microbiome profiling could be a feasible, noninvasive adjunct for monitoring and risk stratification in NMIBC.
DOI: https://doi.org/10.37349/etat.2026.1002365
This review highlights the significant sex-based differences in immune responses to influenza infection and vaccination. Men are generally more susceptible to severe influenza outcomes, while women often mount stronger immune responses but experience more adverse effects. These disparities are influenced by biological factors, including sex hormones and genes, as well as gender-related social and environmental conditions. Evidence from both human and animal studies reveals sex-specific variations in antibody production, vaccine effectiveness, and clinical outcomes. Age, hormonal status, and stress further modulate these differences. Understanding these complex interactions is essential for developing tailored and equitable vaccination and treatment strategies.
This review highlights the significant sex-based differences in immune responses to influenza infection and vaccination. Men are generally more susceptible to severe influenza outcomes, while women often mount stronger immune responses but experience more adverse effects. These disparities are influenced by biological factors, including sex hormones and genes, as well as gender-related social and environmental conditions. Evidence from both human and animal studies reveals sex-specific variations in antibody production, vaccine effectiveness, and clinical outcomes. Age, hormonal status, and stress further modulate these differences. Understanding these complex interactions is essential for developing tailored and equitable vaccination and treatment strategies.
DOI: https://doi.org/10.37349/ei.2026.1003244
Breast cancer exhibits substantial clinical and molecular heterogeneity, partly shaped by interactions between tumor biology and the host immune system. Germline variants in immune-related genes may influence inflammatory tone, immune regulation, and tumor-immune interactions. However, evidence linking inherited immune genetic variation to breast cancer risk and clinical behavior remains fragmented and heterogeneous across studies. We conducted a structured integrative review of 33 human genetic associations evaluating germline variants in immune-related genes and their associations with breast cancer risk, prognosis, and clinicopathological features. Data were synthesized using a comparative, pathway-oriented analytic framework. Variants in cytokine genes, particularly TGFB1, IL6, IL1B, and IL10, were the most frequently associated with susceptibility, although effect directions varied across populations and genetic models. In contrast, variants in chemokine pathways (CXCL12) and immune checkpoint regulator genes (B7-H4/VTCN1, PD-1/PDCD1) showed consistent associations with tumor progression, immune evasion, and subtype-specific clinical features, including human epidermal growth factor receptor 2 (HER2)-positive disease and metastatic presentation. Across studies, substantial heterogeneity was observed, driven by differences in ethnic composition, sample size, methodological design, and deviations from the Hardy-Weinberg equilibrium. The findings support a pathway-oriented interpretation in which germline immune variation differentially influences immune regulation and tumor progression rather than uniformly determining disease risk. While inflammatory and immunoregulatory pathways appear to shape basal immune tone, immune effector function is less consistently associated with germline variation. Further progress will require extensive, multiethnic studies integrating genetic, transcriptomic, and functional data to clarify how inherited immune variation contributes to breast cancer biology.
Breast cancer exhibits substantial clinical and molecular heterogeneity, partly shaped by interactions between tumor biology and the host immune system. Germline variants in immune-related genes may influence inflammatory tone, immune regulation, and tumor-immune interactions. However, evidence linking inherited immune genetic variation to breast cancer risk and clinical behavior remains fragmented and heterogeneous across studies. We conducted a structured integrative review of 33 human genetic associations evaluating germline variants in immune-related genes and their associations with breast cancer risk, prognosis, and clinicopathological features. Data were synthesized using a comparative, pathway-oriented analytic framework. Variants in cytokine genes, particularly TGFB1, IL6, IL1B, and IL10, were the most frequently associated with susceptibility, although effect directions varied across populations and genetic models. In contrast, variants in chemokine pathways (CXCL12) and immune checkpoint regulator genes (B7-H4/VTCN1, PD-1/PDCD1) showed consistent associations with tumor progression, immune evasion, and subtype-specific clinical features, including human epidermal growth factor receptor 2 (HER2)-positive disease and metastatic presentation. Across studies, substantial heterogeneity was observed, driven by differences in ethnic composition, sample size, methodological design, and deviations from the Hardy-Weinberg equilibrium. The findings support a pathway-oriented interpretation in which germline immune variation differentially influences immune regulation and tumor progression rather than uniformly determining disease risk. While inflammatory and immunoregulatory pathways appear to shape basal immune tone, immune effector function is less consistently associated with germline variation. Further progress will require extensive, multiethnic studies integrating genetic, transcriptomic, and functional data to clarify how inherited immune variation contributes to breast cancer biology.
DOI: https://doi.org/10.37349/ei.2026.1003245
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction marked by fluctuating muscle weakness, driven by pathogenic antibodies targeting acetylcholine receptors, muscle-specific kinase, or lipoprotein receptor-related protein 4. Traditional treatments such as corticosteroids and immunosuppressants provide symptomatic relief but are limited by systemic toxicity and variable efficacy. Advances in immunology have led to targeted biologics that address specific disease mechanisms, such as B-cell depleting antibodies like rituximab and inebilizumab, complement inhibitors such as eculizumab, ravulizumab, and zilucoplan, and neonatal Fc receptor antagonists like efgartigimod and rozanolixizumab that lower pathogenic IgG levels. Emerging molecular and cellular therapies, including T-regulatory cell therapy, RNA-based modulation, and chimeric antigen receptor T-cell therapy approaches, seek to achieve durable immune tolerance rather than transient suppression. However, therapeutic response varies due to immunologic heterogeneity, long-term safety concerns, and limited global access. Future directions focus on precision medicine, biomarker-guided treatment, and AI-assisted disease monitoring, alongside next-generation therapeutics such as long-acting FcRn inhibitors (IMVT-1402), bispecific antibodies (gefurulimab), and oral small molecules (remibrutinib, iptacopan). Collectively, these developments mark a shift from generalized immunosuppression toward mechanism-based, patient-centered care aimed at restoring lasting immune balance and improving quality of life in MG. This narrative review discusses these aspects to comprehend the existing understanding and challenges.
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction marked by fluctuating muscle weakness, driven by pathogenic antibodies targeting acetylcholine receptors, muscle-specific kinase, or lipoprotein receptor-related protein 4. Traditional treatments such as corticosteroids and immunosuppressants provide symptomatic relief but are limited by systemic toxicity and variable efficacy. Advances in immunology have led to targeted biologics that address specific disease mechanisms, such as B-cell depleting antibodies like rituximab and inebilizumab, complement inhibitors such as eculizumab, ravulizumab, and zilucoplan, and neonatal Fc receptor antagonists like efgartigimod and rozanolixizumab that lower pathogenic IgG levels. Emerging molecular and cellular therapies, including T-regulatory cell therapy, RNA-based modulation, and chimeric antigen receptor T-cell therapy approaches, seek to achieve durable immune tolerance rather than transient suppression. However, therapeutic response varies due to immunologic heterogeneity, long-term safety concerns, and limited global access. Future directions focus on precision medicine, biomarker-guided treatment, and AI-assisted disease monitoring, alongside next-generation therapeutics such as long-acting FcRn inhibitors (IMVT-1402), bispecific antibodies (gefurulimab), and oral small molecules (remibrutinib, iptacopan). Collectively, these developments mark a shift from generalized immunosuppression toward mechanism-based, patient-centered care aimed at restoring lasting immune balance and improving quality of life in MG. This narrative review discusses these aspects to comprehend the existing understanding and challenges.
DOI: https://doi.org/10.37349/ei.2026.1003246
This article belongs to the special issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases
Aim:
This study evaluated the comparative effects of commonly consumed artificial and natural sweeteners on cognitive function, neurotransmitter-related enzyme activities, and oxidative stress status in the brains of Wistar rats to elucidate their potential neurotoxic or neuroprotective properties under sub-chronic dietary exposure.
Methods:
Seventy-two male Wistar rats were randomly assigned to twelve groups and fed composite biscuits formulated with sucrose (15% and 30%), aspartame (3.5% and 7.0%), date sugar (10% and 20%), erythritol (15% and 30%), or stevia (2.5% and 5.0%) for 21 days. Control groups received either a basal diet or plain wheat biscuits. Spatial working memory was assessed using the Y-Maze spontaneous alternation test. Hippocampal tissue was harvested to determine monoamine oxidase (MAO), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activities, lipid peroxidation (TBARS, thiobarbituric acid-reactive substances), reactive oxygen species (ROS) production, and antioxidant enzyme activities (superoxide dismutase, catalase, glutathione-S-transferase (GST), and glutathione peroxidase).
Results:
Sucrose (15% and 30%) and aspartame (3.5% and 7.0%) significantly reduced spontaneous alternation performance, indicating impaired working memory. Both sucrose and aspartame dosages markedly elevated MAO, AChE, and BChE activities, increased TBARS and ROS levels, and suppressed antioxidant enzyme activities in the hippocampus. In contrast, diets containing date sugar and erythritol preserved cognitive performance and maintained neurochemical and redox homeostasis. Notably, stevia (5.0%) significantly reduced MAO and AChE activities, attenuated oxidative stress markers, and enhanced endogenous antioxidant defenses.
Conclusions:
Sub-chronic consumption of sucrose and aspartame induces hippocampal neurotransmitter dysregulation and oxidative stress, contributing to cognitive impairment, whereas natural sweeteners, particularly stevia and date sugar, exhibit neuroprotective effects. These findings support the preferential use of natural sweeteners as safer dietary alternatives for maintaining cognitive and neurochemical health.
Aim:
This study evaluated the comparative effects of commonly consumed artificial and natural sweeteners on cognitive function, neurotransmitter-related enzyme activities, and oxidative stress status in the brains of Wistar rats to elucidate their potential neurotoxic or neuroprotective properties under sub-chronic dietary exposure.
Methods:
Seventy-two male Wistar rats were randomly assigned to twelve groups and fed composite biscuits formulated with sucrose (15% and 30%), aspartame (3.5% and 7.0%), date sugar (10% and 20%), erythritol (15% and 30%), or stevia (2.5% and 5.0%) for 21 days. Control groups received either a basal diet or plain wheat biscuits. Spatial working memory was assessed using the Y-Maze spontaneous alternation test. Hippocampal tissue was harvested to determine monoamine oxidase (MAO), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activities, lipid peroxidation (TBARS, thiobarbituric acid-reactive substances), reactive oxygen species (ROS) production, and antioxidant enzyme activities (superoxide dismutase, catalase, glutathione-S-transferase (GST), and glutathione peroxidase).
Results:
Sucrose (15% and 30%) and aspartame (3.5% and 7.0%) significantly reduced spontaneous alternation performance, indicating impaired working memory. Both sucrose and aspartame dosages markedly elevated MAO, AChE, and BChE activities, increased TBARS and ROS levels, and suppressed antioxidant enzyme activities in the hippocampus. In contrast, diets containing date sugar and erythritol preserved cognitive performance and maintained neurochemical and redox homeostasis. Notably, stevia (5.0%) significantly reduced MAO and AChE activities, attenuated oxidative stress markers, and enhanced endogenous antioxidant defenses.
Conclusions:
Sub-chronic consumption of sucrose and aspartame induces hippocampal neurotransmitter dysregulation and oxidative stress, contributing to cognitive impairment, whereas natural sweeteners, particularly stevia and date sugar, exhibit neuroprotective effects. These findings support the preferential use of natural sweeteners as safer dietary alternatives for maintaining cognitive and neurochemical health.
DOI: https://doi.org/10.37349/eff.2026.1010132
This article belongs to the special issue Neuroprotective Potential of Natural Products from Foods
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease of undefined etiology. In recent years, its global incidence has shown an upward trend, with a median survival of approximately 3–5 years after diagnosis. Currently, clinical treatment outcomes for this disease remain limited. Approved therapeutic agents are nintedanib, pirfenidone, and nerandomilast, all of which are predominantly administered orally. The oral route renders drugs susceptible to degradation in the gastrointestinal tract, leading to reduced drug bioavailability and limited therapeutic efficacy. In this work, we believe that nanodelivery systems (NDSs) represent a promising approach to address the limitations of traditional therapies. Most importantly, we emphasized that inhalation NDSs should be prioritized to enhance the accumulation efficiency of targeted drugs at pulmonary lesion sites. Collectively, this study aims to provide insights into the developmental prospects of NDSs for IPF, paving the way for more efficient and personalized therapeutic approaches to enhance treatment efficacy while minimizing side effects.
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease of undefined etiology. In recent years, its global incidence has shown an upward trend, with a median survival of approximately 3–5 years after diagnosis. Currently, clinical treatment outcomes for this disease remain limited. Approved therapeutic agents are nintedanib, pirfenidone, and nerandomilast, all of which are predominantly administered orally. The oral route renders drugs susceptible to degradation in the gastrointestinal tract, leading to reduced drug bioavailability and limited therapeutic efficacy. In this work, we believe that nanodelivery systems (NDSs) represent a promising approach to address the limitations of traditional therapies. Most importantly, we emphasized that inhalation NDSs should be prioritized to enhance the accumulation efficiency of targeted drugs at pulmonary lesion sites. Collectively, this study aims to provide insights into the developmental prospects of NDSs for IPF, paving the way for more efficient and personalized therapeutic approaches to enhance treatment efficacy while minimizing side effects.
DOI: https://doi.org/10.37349/emed.2026.1001397
Aim:
Polypharmacy is increasingly prevalent among older adults and has been suggested as a potential risk factor for adverse health outcomes, including cognitive impairment and functional decline. Therefore, this study aimed to investigate the associations of polypharmacy with cognitive impairment and functional status among community-dwelling older adults using nationally representative data from the 2023 Korean Elderly Survey.
Methods:
A cross-sectional analysis was conducted using data from 9,898 community-dwelling older adults without a diagnosis of dementia. Polypharmacy was defined as the concurrent use of five or more physician-prescribed medications. Cognitive function was assessed using the Korean version of the Mini-Mental State Examination (K-MMSE), with cognitive impairment defined as a score ≤ 23. Functional status was evaluated using the Korean Activities of Daily Living (K-ADL) and Korean Instrumental Activities of Daily Living (K-IADL). Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for cognitive impairment, while multiple linear regression analyses examined associations with functional status. Models were sequentially adjusted for sociodemographic characteristics, health behaviors, and the number of chronic diseases.
Results:
Polypharmacy was associated with increased odds of cognitive impairment in the crude model (OR = 1.70, 95% CI: 1.40–2.05); however, this association was attenuated and became non-significant after adjustment for sociodemographic and health-related factors. In contrast, polypharmacy remained independently associated with poorer functional status in fully adjusted models, showing higher K-ADL scores (B = 0.14, p = 0.007) and K-IADL scores (B = 0.43, p < 0.001).
Conclusions:
Polypharmacy was independently associated with functional impairment but not with cognitive impairment after comprehensive adjustment, suggesting that functional decline may represent a more sensitive and immediate consequence of complex medication use in older adults. These findings underscore the need for comprehensive geriatric assessment approaches that integrate medication review with functional evaluation.
Aim:
Polypharmacy is increasingly prevalent among older adults and has been suggested as a potential risk factor for adverse health outcomes, including cognitive impairment and functional decline. Therefore, this study aimed to investigate the associations of polypharmacy with cognitive impairment and functional status among community-dwelling older adults using nationally representative data from the 2023 Korean Elderly Survey.
Methods:
A cross-sectional analysis was conducted using data from 9,898 community-dwelling older adults without a diagnosis of dementia. Polypharmacy was defined as the concurrent use of five or more physician-prescribed medications. Cognitive function was assessed using the Korean version of the Mini-Mental State Examination (K-MMSE), with cognitive impairment defined as a score ≤ 23. Functional status was evaluated using the Korean Activities of Daily Living (K-ADL) and Korean Instrumental Activities of Daily Living (K-IADL). Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for cognitive impairment, while multiple linear regression analyses examined associations with functional status. Models were sequentially adjusted for sociodemographic characteristics, health behaviors, and the number of chronic diseases.
Results:
Polypharmacy was associated with increased odds of cognitive impairment in the crude model (OR = 1.70, 95% CI: 1.40–2.05); however, this association was attenuated and became non-significant after adjustment for sociodemographic and health-related factors. In contrast, polypharmacy remained independently associated with poorer functional status in fully adjusted models, showing higher K-ADL scores (B = 0.14, p = 0.007) and K-IADL scores (B = 0.43, p < 0.001).
Conclusions:
Polypharmacy was independently associated with functional impairment but not with cognitive impairment after comprehensive adjustment, suggesting that functional decline may represent a more sensitive and immediate consequence of complex medication use in older adults. These findings underscore the need for comprehensive geriatric assessment approaches that integrate medication review with functional evaluation.
DOI: https://doi.org/10.37349/emed.2026.1001398
Hepatocellular carcinoma (HCC) functions as a major cancer-related death factor around the world. Research indicates that long non-coding RNAs (lncRNAs) play essential roles during HCC onset and development because they belong to the novel RNA subclass that extends beyond 200 nucleotides without protein-coding capability. LncRNAs regulate the expression of downstream target genes and cancer-related signaling pathways, thereby promoting the proliferation, migration, invasion, autophagy, and apoptosis of tumor cells. The study of lncRNA function has been substantially facilitated by the emergence of lncRNA-specific microarrays and the increased accessibility of next-generation sequencing technologies. The function of lncRNAs can be predicted using computational and molecular methodologies. LncRNAs have the potential to function as repressors, scaffolds, regulators of super-enhancers, or molecular decoys. Proliferation, invasion, survival, DNA damage response (DDR), and chromatin dynamics can all be influenced by lncRNAs. Additionally, they can affect stemness/differentiation. The recurrence of tumors may be facilitated by the aberrant expression of these transcripts, which may result in therapy resistance. LncRNAs have the potential to function as innovative prognostic or theranostic biomarkers in HCC and other malignancies. In addition, RNA-based therapeutics may be implemented to target lncRNAs as a novel treatment approach for primary or recurrent HCC. In this review, we investigate the functions of lncRNAs in the pathophysiology of HCC and suggest their potential for novel therapeutic application in the treatment of HCC.
Hepatocellular carcinoma (HCC) functions as a major cancer-related death factor around the world. Research indicates that long non-coding RNAs (lncRNAs) play essential roles during HCC onset and development because they belong to the novel RNA subclass that extends beyond 200 nucleotides without protein-coding capability. LncRNAs regulate the expression of downstream target genes and cancer-related signaling pathways, thereby promoting the proliferation, migration, invasion, autophagy, and apoptosis of tumor cells. The study of lncRNA function has been substantially facilitated by the emergence of lncRNA-specific microarrays and the increased accessibility of next-generation sequencing technologies. The function of lncRNAs can be predicted using computational and molecular methodologies. LncRNAs have the potential to function as repressors, scaffolds, regulators of super-enhancers, or molecular decoys. Proliferation, invasion, survival, DNA damage response (DDR), and chromatin dynamics can all be influenced by lncRNAs. Additionally, they can affect stemness/differentiation. The recurrence of tumors may be facilitated by the aberrant expression of these transcripts, which may result in therapy resistance. LncRNAs have the potential to function as innovative prognostic or theranostic biomarkers in HCC and other malignancies. In addition, RNA-based therapeutics may be implemented to target lncRNAs as a novel treatment approach for primary or recurrent HCC. In this review, we investigate the functions of lncRNAs in the pathophysiology of HCC and suggest their potential for novel therapeutic application in the treatment of HCC.
DOI: https://doi.org/10.37349/edd.2026.1005120
This article belongs to the special issue Prevention, Screening and Diagnosis for Primary Liver Cancer
Aim:
Enteral nutrition (EN) improves patient health. However, the use of fresh produce may increase the risk of parasitic contamination. Recovery of parasites from enteral formulations is challenging and no studies have yet addressed this issue. The primary goal of this study was to standardize methodologies for detecting helminth eggs in different enteral formulations prepared with fresh produce, aiming to establish a reproducible protocol for food safety assessments.
Methods:
Two homemade enteral preparations (HEP) with mixed raw fresh fruits or vegetables were produced and artificially contaminated with two doses of Ascaris suum eggs (1 = 207 and 2 = 76 eggs). HEP 1 contained cabbage, orange juice, lettuce, watercress, and filtered water, while HEP 2 consisted of strawberries and filtered water. To estimate the egg recovery rate, four protocols per preparation/dose were analyzed in triplicate (48 trials total). The following variables were evaluated: homogenization (manual or using a magnetic stirrer) and dispersion solution (1 M glycine, pH 5.5 or 0.1% Alconox®). All protocols shared the following steps: sedimentation, centrifugation, and total sediment analysis.
Results:
The highest recovery efficiency for HEP 1 was achieved with Protocol 2 (glycine + magnetic stirrer), with averages of 66% (Dose 1) and 55% (Dose 2). For HEP 2, Protocol 4 (Alconox® + magnetic stirrer) performed best, yielding 66% (Dose 1) and 52% (Dose 2). Viable eggs of Toxocara sp., and hookworm were naturally detected in HEP 1 and 2, respectively.
Conclusions:
This is the first study to standardize and measure the detection sensitivity of a methodology for detecting parasites in enteral formulations. Since most patients receiving these types of food require intensive care, strict quality control is essential, including evaluation of the parasitological quality of EN to avoid exacerbating their already compromised health.
Aim:
Enteral nutrition (EN) improves patient health. However, the use of fresh produce may increase the risk of parasitic contamination. Recovery of parasites from enteral formulations is challenging and no studies have yet addressed this issue. The primary goal of this study was to standardize methodologies for detecting helminth eggs in different enteral formulations prepared with fresh produce, aiming to establish a reproducible protocol for food safety assessments.
Methods:
Two homemade enteral preparations (HEP) with mixed raw fresh fruits or vegetables were produced and artificially contaminated with two doses of Ascaris suum eggs (1 = 207 and 2 = 76 eggs). HEP 1 contained cabbage, orange juice, lettuce, watercress, and filtered water, while HEP 2 consisted of strawberries and filtered water. To estimate the egg recovery rate, four protocols per preparation/dose were analyzed in triplicate (48 trials total). The following variables were evaluated: homogenization (manual or using a magnetic stirrer) and dispersion solution (1 M glycine, pH 5.5 or 0.1% Alconox®). All protocols shared the following steps: sedimentation, centrifugation, and total sediment analysis.
Results:
The highest recovery efficiency for HEP 1 was achieved with Protocol 2 (glycine + magnetic stirrer), with averages of 66% (Dose 1) and 55% (Dose 2). For HEP 2, Protocol 4 (Alconox® + magnetic stirrer) performed best, yielding 66% (Dose 1) and 52% (Dose 2). Viable eggs of Toxocara sp., and hookworm were naturally detected in HEP 1 and 2, respectively.
Conclusions:
This is the first study to standardize and measure the detection sensitivity of a methodology for detecting parasites in enteral formulations. Since most patients receiving these types of food require intensive care, strict quality control is essential, including evaluation of the parasitological quality of EN to avoid exacerbating their already compromised health.
DOI: https://doi.org/10.37349/eff.2026.1010133
The relationship between the gut microbiota and the central nervous system has gained attention as a biological axis that may influence the development of several neurological disorders. Recent evidence integrating genomic, neurobiological, and microbiota research shows how bacterial composition, host genetic variability, and the mechanisms of the microbiota-gut-brain axis interact in conditions such as autism spectrum disorder, epilepsy, and schizophrenia. These interactions function through neural, metabolic, and immunological related pathways involving intestinal and blood-brain barrier permeability. Genome-wide association studies (GWAS) and Mendelian randomization analyses highlight shared immunogenetic pathways that may shape both microbial profiles and neurological susceptibility. Consistent patterns of dysbiosis and alterations in neuroactive metabolites have also been reported, linking microbiota changes to neuroinflammation and disrupted neuronal signaling. This review synthesizes the current evidence supporting the integration of the microbiota-gut-brain axis and its underlying communication pathways. It also outlines the present therapeutic strategies for neurological disorders such as autism spectrum disorder, epilepsy, and schizophrenia, highlighting their potential to modulate neurological function. Additionally, it discusses the existing limitations in the field and offers insights into future research directions within this rapidly evolving area.
The relationship between the gut microbiota and the central nervous system has gained attention as a biological axis that may influence the development of several neurological disorders. Recent evidence integrating genomic, neurobiological, and microbiota research shows how bacterial composition, host genetic variability, and the mechanisms of the microbiota-gut-brain axis interact in conditions such as autism spectrum disorder, epilepsy, and schizophrenia. These interactions function through neural, metabolic, and immunological related pathways involving intestinal and blood-brain barrier permeability. Genome-wide association studies (GWAS) and Mendelian randomization analyses highlight shared immunogenetic pathways that may shape both microbial profiles and neurological susceptibility. Consistent patterns of dysbiosis and alterations in neuroactive metabolites have also been reported, linking microbiota changes to neuroinflammation and disrupted neuronal signaling. This review synthesizes the current evidence supporting the integration of the microbiota-gut-brain axis and its underlying communication pathways. It also outlines the present therapeutic strategies for neurological disorders such as autism spectrum disorder, epilepsy, and schizophrenia, highlighting their potential to modulate neurological function. Additionally, it discusses the existing limitations in the field and offers insights into future research directions within this rapidly evolving area.
DOI: https://doi.org/10.37349/ent.2026.1004146
This article belongs to the special issue Role of Microbiota in Neurological Diseases
Background:
Acquired brain injury (ABI) often causes long-lasting impairments in written language and handwriting that limit autonomy and daily functioning. Despite their relevance, these deficits have received limited research attention compared with spoken language disorders. The present work aims to systematically review interventions designed to improve reading, writing, and handwriting abilities in individuals with ABI.
Methods:
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, American Psychological Association (APA) PsycINFO, Cochrane Library, Web of Science, and Google Scholar were searched from inception to 1 November 2025. Eligible studies were randomized or non-randomized clinical trials (non-RCTs) involving adults or adolescents with ABI and documented written language impairments. Risk of bias was assessed using the Risk of Bias 2 tool (RCTs) and Risk of Bias in Non-randomized Studies—of Interventions tool (non-RCTs).
Results:
Twelve studies met inclusion criteria (2 RCTs, 10 non-RCTs), all conducted in post-stroke populations, highlighting the absence of evidence from other ABI aetiologies. Three main intervention categories emerged: (1) Behavioral treatments, which consistently improved trained spelling and functional writing, with some advantages for errorless learning in maintaining gains. (2) Technology-assisted approaches, including assistive software, digital spelling aids, and handwriting-focused programs, which showed feasibility, high usability, and improvements in accuracy, legibility, and motor fluency. (3) Neuromodulation, with one RCT showing that dual-site transcranial direct current stimulation can modestly enhance behavioral writing therapy. Most non-RCTs showed serious or critical risk of bias, and sample sizes were small, limiting generalizability.
Discussion:
Current evidence—although preliminary and restricted to post-stroke ABI—indicates that behavioral, technological, and neuromodulatory interventions can improve aspects of written language and handwriting after ABI. However, the available literature is characterized by small samples, substantial methodological variability, and a paucity of standardized and ecologically valid outcome measures. High-quality, adequately powered trials with standardized, functional outcomes are urgently needed, particularly in non-stroke ABI populations.
Background:
Acquired brain injury (ABI) often causes long-lasting impairments in written language and handwriting that limit autonomy and daily functioning. Despite their relevance, these deficits have received limited research attention compared with spoken language disorders. The present work aims to systematically review interventions designed to improve reading, writing, and handwriting abilities in individuals with ABI.
Methods:
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, American Psychological Association (APA) PsycINFO, Cochrane Library, Web of Science, and Google Scholar were searched from inception to 1 November 2025. Eligible studies were randomized or non-randomized clinical trials (non-RCTs) involving adults or adolescents with ABI and documented written language impairments. Risk of bias was assessed using the Risk of Bias 2 tool (RCTs) and Risk of Bias in Non-randomized Studies—of Interventions tool (non-RCTs).
Results:
Twelve studies met inclusion criteria (2 RCTs, 10 non-RCTs), all conducted in post-stroke populations, highlighting the absence of evidence from other ABI aetiologies. Three main intervention categories emerged: (1) Behavioral treatments, which consistently improved trained spelling and functional writing, with some advantages for errorless learning in maintaining gains. (2) Technology-assisted approaches, including assistive software, digital spelling aids, and handwriting-focused programs, which showed feasibility, high usability, and improvements in accuracy, legibility, and motor fluency. (3) Neuromodulation, with one RCT showing that dual-site transcranial direct current stimulation can modestly enhance behavioral writing therapy. Most non-RCTs showed serious or critical risk of bias, and sample sizes were small, limiting generalizability.
Discussion:
Current evidence—although preliminary and restricted to post-stroke ABI—indicates that behavioral, technological, and neuromodulatory interventions can improve aspects of written language and handwriting after ABI. However, the available literature is characterized by small samples, substantial methodological variability, and a paucity of standardized and ecologically valid outcome measures. High-quality, adequately powered trials with standardized, functional outcomes are urgently needed, particularly in non-stroke ABI populations.
DOI: https://doi.org/10.37349/ent.2026.1004145
This article belongs to the special issue Neuropsychology of Handwriting
Background:
Fully immersive virtual reality (IVR) is an emerging technology approach for cognitive training in individuals with mild cognitive impairment (MCI) and dementia. While interest in fully IVR continues to grow, it remains unclear the extent of effectiveness and the key components that contribute to successful implementation. This study aimed to explore the effectiveness of fully IVR cognitive training for individuals with MCI or dementia from previous research literature.
Methods:
A scoping review was conducted using a systematic search strategy based on the population, concept, and context framework.
Results:
Out of the 816 records identified, 123 full texts were screened, and eight studies were included in the review. The included studies all involved participants completing a cognitive training intervention using fully IVR headsets, with cognitive outcomes measured before and after the intervention. The most consistent improvements across the included studies were executive function, memory, and visuospatial abilities. Only two studies explicitly referenced a theoretical model.
Discussion:
Fully IVR cognitive training demonstrates promise for improving specific cognitive domains in individuals living with MCI or dementia. However, inconsistencies in outcomes and limited theoretical grounding highlight the need for further exploration. Broader considerations are discussed in the discussion section.
Background:
Fully immersive virtual reality (IVR) is an emerging technology approach for cognitive training in individuals with mild cognitive impairment (MCI) and dementia. While interest in fully IVR continues to grow, it remains unclear the extent of effectiveness and the key components that contribute to successful implementation. This study aimed to explore the effectiveness of fully IVR cognitive training for individuals with MCI or dementia from previous research literature.
Methods:
A scoping review was conducted using a systematic search strategy based on the population, concept, and context framework.
Results:
Out of the 816 records identified, 123 full texts were screened, and eight studies were included in the review. The included studies all involved participants completing a cognitive training intervention using fully IVR headsets, with cognitive outcomes measured before and after the intervention. The most consistent improvements across the included studies were executive function, memory, and visuospatial abilities. Only two studies explicitly referenced a theoretical model.
Discussion:
Fully IVR cognitive training demonstrates promise for improving specific cognitive domains in individuals living with MCI or dementia. However, inconsistencies in outcomes and limited theoretical grounding highlight the need for further exploration. Broader considerations are discussed in the discussion section.
DOI: https://doi.org/10.37349/ent.2026.1004144
This article belongs to the special issue Innovations in Neurotechnology: Integrating AI, Neuroimaging, and VR for the Assessment and Treatment of Neurological Conditions
Osteoarthritis (OA) is the most prevalent form of arthritis and a leading cause of disability worldwide. Epidemiological studies indicate that its global prevalence is rising, particularly among women, who often experience more severe disease than men. This sex disparity is most pronounced around menopause and is influenced by female-specific biological and hormonal factors, joint morphology, reproductive history, and sex-specific comorbidities that contribute to disease onset and progression. A mechanistic understanding of these factors is essential to identify individuals at risk, implement preventive strategies, enable early diagnosis, and mitigate complications, ultimately preserving function and quality of life. This review focuses on the determinants underlying the higher incidence and severity of OA in women, highlighting the interplay between hormonal changes, anatomy, and systemic factors.
Osteoarthritis (OA) is the most prevalent form of arthritis and a leading cause of disability worldwide. Epidemiological studies indicate that its global prevalence is rising, particularly among women, who often experience more severe disease than men. This sex disparity is most pronounced around menopause and is influenced by female-specific biological and hormonal factors, joint morphology, reproductive history, and sex-specific comorbidities that contribute to disease onset and progression. A mechanistic understanding of these factors is essential to identify individuals at risk, implement preventive strategies, enable early diagnosis, and mitigate complications, ultimately preserving function and quality of life. This review focuses on the determinants underlying the higher incidence and severity of OA in women, highlighting the interplay between hormonal changes, anatomy, and systemic factors.
DOI: https://doi.org/10.37349/eemd.2026.101466
Acute mesenteric ischemia (AMI) is a rare but highly lethal vascular emergency resulting from the abrupt interruption of intestinal blood flow. In advanced stages, extensive bowel necrosis may require near total enterectomy, leading to short bowel syndrome and permanent dependence on parenteral nutrition. An 86-year-old woman with atrial fibrillation and multiple cardiometabolic comorbidities presented with acute abdominal pain, nausea, and vomiting. Initial laboratory findings revealed marked leukocytosis and severe systemic inflammation (CRP: 21.0 mg/L). Computed tomography (CT) angiography demonstrated impaired perfusion of the superior mesenteric artery. Emergency laparotomy confirmed extensive jejunoileal ischemic necrosis, necessitating near total enterectomy with stapled jejunoileal anastomosis. Second-look surgery revealed progressive ischemia of the ileocecal region and right colon, requiring extended right hemicolectomy. Postoperatively, the patient was managed with total parenteral nutrition and intensive supportive care. Despite temporary stabilization and discharge on home parenteral nutrition, she died six months later. AMI complicated by short bowel syndrome is associated with poor prognosis in elderly patients. Persistent systemic inflammation, progressive organ dysfunction, and intestinal failure remain major determinants of adverse long-term outcomes, highlighting the critical importance of early diagnosis, prompt surgical intervention, and multidisciplinary postoperative management.
Acute mesenteric ischemia (AMI) is a rare but highly lethal vascular emergency resulting from the abrupt interruption of intestinal blood flow. In advanced stages, extensive bowel necrosis may require near total enterectomy, leading to short bowel syndrome and permanent dependence on parenteral nutrition. An 86-year-old woman with atrial fibrillation and multiple cardiometabolic comorbidities presented with acute abdominal pain, nausea, and vomiting. Initial laboratory findings revealed marked leukocytosis and severe systemic inflammation (CRP: 21.0 mg/L). Computed tomography (CT) angiography demonstrated impaired perfusion of the superior mesenteric artery. Emergency laparotomy confirmed extensive jejunoileal ischemic necrosis, necessitating near total enterectomy with stapled jejunoileal anastomosis. Second-look surgery revealed progressive ischemia of the ileocecal region and right colon, requiring extended right hemicolectomy. Postoperatively, the patient was managed with total parenteral nutrition and intensive supportive care. Despite temporary stabilization and discharge on home parenteral nutrition, she died six months later. AMI complicated by short bowel syndrome is associated with poor prognosis in elderly patients. Persistent systemic inflammation, progressive organ dysfunction, and intestinal failure remain major determinants of adverse long-term outcomes, highlighting the critical importance of early diagnosis, prompt surgical intervention, and multidisciplinary postoperative management.
DOI: https://doi.org/10.37349/edd.2026.1005119
Genistein, a soy-derived isoflavone, has attracted considerable interest for its anti-inflammatory and anticancer properties. Chronic inflammation is a major driver of tumour initiation, progression, metastasis, and therapeutic resistance, creating a need for multi-target agents capable of modulating both inflammatory and oncogenic pathways. This review critically evaluates the molecular mechanisms, pharmacological basis, and translational prospects of genistein in inflammation-related cancers, incorporating recent advances in omics technologies and nanotechnology-based delivery systems. A comprehensive survey of the literature from major scientific databases was conducted, and evidence was assessed based on mechanistic depth, strength of data, and relevance to clinical translation. Genistein modulates multiple interconnected signalling pathways, including NF-κB, MAPK, PI3K/Akt, JAK/STAT, and apoptotic cascades, leading to reduced pro-inflammatory cytokine production, oxidative stress, and tumour cell proliferation. Epigenetic regulation, growth-factor pathway inhibition, and non-coding RNA modulation further contribute to its pleiotropic effects. Nanotechnology-based delivery platforms are being explored to improve their poor oral bioavailability and therapeutic performance in preclinical models. However, clinical translation remains limited by low bioavailability, context-dependent estrogenic activity, inter-individual metabolic variability, and the lack of large-scale, well-controlled clinical trials, standardized dosing, and validated biomarkers. Genistein represents a promising multi-target lead compound at the intersection of inflammation, immunology, and oncology, with future progress dependent on integrating multi-omics data and advanced delivery technologies for personalised clinical applications.
Genistein, a soy-derived isoflavone, has attracted considerable interest for its anti-inflammatory and anticancer properties. Chronic inflammation is a major driver of tumour initiation, progression, metastasis, and therapeutic resistance, creating a need for multi-target agents capable of modulating both inflammatory and oncogenic pathways. This review critically evaluates the molecular mechanisms, pharmacological basis, and translational prospects of genistein in inflammation-related cancers, incorporating recent advances in omics technologies and nanotechnology-based delivery systems. A comprehensive survey of the literature from major scientific databases was conducted, and evidence was assessed based on mechanistic depth, strength of data, and relevance to clinical translation. Genistein modulates multiple interconnected signalling pathways, including NF-κB, MAPK, PI3K/Akt, JAK/STAT, and apoptotic cascades, leading to reduced pro-inflammatory cytokine production, oxidative stress, and tumour cell proliferation. Epigenetic regulation, growth-factor pathway inhibition, and non-coding RNA modulation further contribute to its pleiotropic effects. Nanotechnology-based delivery platforms are being explored to improve their poor oral bioavailability and therapeutic performance in preclinical models. However, clinical translation remains limited by low bioavailability, context-dependent estrogenic activity, inter-individual metabolic variability, and the lack of large-scale, well-controlled clinical trials, standardized dosing, and validated biomarkers. Genistein represents a promising multi-target lead compound at the intersection of inflammation, immunology, and oncology, with future progress dependent on integrating multi-omics data and advanced delivery technologies for personalised clinical applications.
DOI: https://doi.org/10.37349/ei.2026.1003243
Telepsychiatry has transitioned from a supplementary modality to a sustained component of contemporary mental healthcare, driven by technological advancement, workforce shortages, and the COVID-19 pandemic. This narrative review synthesizes current evidence on clinical effectiveness, service models, technological integration, and ethical–legal considerations, and contextualizes these domains through institutional implementation experience in Türkiye. Across major diagnostic groups, including mood, anxiety, psychotic, neurodevelopmental, and substance use disorders, published studies generally indicate comparable outcomes and patient satisfaction to face-to-face care when delivered within structured clinical frameworks. We further articulate the theoretical foundations of clinical equivalence, emphasizing language-mediated therapeutic mechanisms, alliance formation in video-based settings, and behavioral factors influencing adherence. The manuscript introduces a system-level perspective for Türkiye, positioning telepsychiatry as a capacity-extending model within geographically uneven workforce distribution. Institutional applications, including disaster response, postpartum screening pathways, and hybrid specialty clinics, illustrate context-sensitive implementation strategies. Emerging innovations such as digital phenotyping, artificial intelligence, and virtual reality are discussed alongside regulatory, equity, and data governance considerations. We conclude that telepsychiatry represents not merely an emergency substitute but an increasingly integrated and policy-relevant model of care.
Telepsychiatry has transitioned from a supplementary modality to a sustained component of contemporary mental healthcare, driven by technological advancement, workforce shortages, and the COVID-19 pandemic. This narrative review synthesizes current evidence on clinical effectiveness, service models, technological integration, and ethical–legal considerations, and contextualizes these domains through institutional implementation experience in Türkiye. Across major diagnostic groups, including mood, anxiety, psychotic, neurodevelopmental, and substance use disorders, published studies generally indicate comparable outcomes and patient satisfaction to face-to-face care when delivered within structured clinical frameworks. We further articulate the theoretical foundations of clinical equivalence, emphasizing language-mediated therapeutic mechanisms, alliance formation in video-based settings, and behavioral factors influencing adherence. The manuscript introduces a system-level perspective for Türkiye, positioning telepsychiatry as a capacity-extending model within geographically uneven workforce distribution. Institutional applications, including disaster response, postpartum screening pathways, and hybrid specialty clinics, illustrate context-sensitive implementation strategies. Emerging innovations such as digital phenotyping, artificial intelligence, and virtual reality are discussed alongside regulatory, equity, and data governance considerations. We conclude that telepsychiatry represents not merely an emergency substitute but an increasingly integrated and policy-relevant model of care.
DOI: https://doi.org/10.37349/edht.2026.101190
This article belongs to the special issue Telepsychiatry in Low-and Middle-income Countries: an Update
Exploring long non-coding RNAs (lncRNAs) in liver diseases, particularly liver fibrosis, presents significant opportunities for augmenting our understanding and treatment of these conditions. The rapid advancement of high-throughput sequencing technologies has revealed the complex networks of lncRNAs, highlighting their crucial functions in liver fibrosis. Identifying dysregulated lncRNAs offers promising diagnostic and prognostic biomarkers, as well as potential therapeutic targets. Extracellular vesicles contribute to the relevance of lncRNAs by protecting them from degradation and maintaining their activity in circulation, as exemplified by the role of lncRNA H19 in liver fibrosis. LncRNAs are vital in liver pathology, influencing fibrosis and cirrhosis by modulating responses to liver injury from ethanol. They affect inflammation, oxidative stress, and apoptosis through interactions with pathways like NF-κB and microRNA networks. LncRNAs also control hepatic stellate cells, the production of extracellular matrix, and the activation of stem cells, which opens up new ways to treat fibrosis. Ethanol modulates lncRNA expression, impacting liver fibrosis and cirrhosis development. LncRNAs also influence hepatocellular carcinoma progression by affecting cell proliferation, immune response, and tumor growth. Despite these insights, the regulatory networks and molecular mechanisms of lncRNAs in liver disorders are not entirely understood. In this review, we focus on unraveling these complexities and identifying effective lncRNAs that could revolutionize liver disease treatment, offer novel diagnostic and therapeutic avenues, and improve patient outcomes.
Exploring long non-coding RNAs (lncRNAs) in liver diseases, particularly liver fibrosis, presents significant opportunities for augmenting our understanding and treatment of these conditions. The rapid advancement of high-throughput sequencing technologies has revealed the complex networks of lncRNAs, highlighting their crucial functions in liver fibrosis. Identifying dysregulated lncRNAs offers promising diagnostic and prognostic biomarkers, as well as potential therapeutic targets. Extracellular vesicles contribute to the relevance of lncRNAs by protecting them from degradation and maintaining their activity in circulation, as exemplified by the role of lncRNA H19 in liver fibrosis. LncRNAs are vital in liver pathology, influencing fibrosis and cirrhosis by modulating responses to liver injury from ethanol. They affect inflammation, oxidative stress, and apoptosis through interactions with pathways like NF-κB and microRNA networks. LncRNAs also control hepatic stellate cells, the production of extracellular matrix, and the activation of stem cells, which opens up new ways to treat fibrosis. Ethanol modulates lncRNA expression, impacting liver fibrosis and cirrhosis development. LncRNAs also influence hepatocellular carcinoma progression by affecting cell proliferation, immune response, and tumor growth. Despite these insights, the regulatory networks and molecular mechanisms of lncRNAs in liver disorders are not entirely understood. In this review, we focus on unraveling these complexities and identifying effective lncRNAs that could revolutionize liver disease treatment, offer novel diagnostic and therapeutic avenues, and improve patient outcomes.
DOI: https://doi.org/10.37349/edd.2026.1005118
This article belongs to the special issue Cirrhosis and Its Complications
Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a respiratory illness characterized by chronic eosinophilic airway inflammation. Although a typical clinical history of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and respiratory reactions to NSAIDs may strongly suggest the diagnosis, history alone is often unreliable due to NSAID avoidance, atypical reactions, or incomplete symptom recognition. In this context, aspirin provocation tests remain the diagnostic gold standard for confirming N-ERD. Beyond diagnostic confirmation, aspirin provocation testing provides critical insights into disease heterogeneity and phenotyping. Different challenge routes—nasal, bronchial, and oral—allow assessment of organ-specific sensitivity and inflammatory dominance. Nasal aspirin provocation primarily reflects upper airway involvement and is particularly informative in patients with severe CRSwNP, whereas inhalational lysine-aspirin challenges highlight lower-airway bronchial hyperresponsiveness. Oral aspirin provocation, through systemic exposure, captures the full spectrum of respiratory and extra-respiratory responses and therefore best reflects global disease severity. The pattern, timing, and intensity of reactions observed during provocation testing contribute to the identification of clinically relevant N-ERD subphenotypes, such as upper-airway-dominant disease, bronchial-predominant disease, or blended reactions involving both compartments. These phenotypic distinctions have direct therapeutic implications, influencing the selection of targeted treatments, including aspirin desensitization, biologic therapies, or surgical interventions. Moreover, provocation testing remains essential prior to aspirin desensitization to ensure both diagnostic accuracy and patient safety. Aspirin provocation tests are not merely confirmatory tools but represent a cornerstone of precision-based evaluation of N-ERD, enabling refined phenotyping, risk stratification, and individualized treatment planning in this complex and heterogeneous disease.
Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a respiratory illness characterized by chronic eosinophilic airway inflammation. Although a typical clinical history of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and respiratory reactions to NSAIDs may strongly suggest the diagnosis, history alone is often unreliable due to NSAID avoidance, atypical reactions, or incomplete symptom recognition. In this context, aspirin provocation tests remain the diagnostic gold standard for confirming N-ERD. Beyond diagnostic confirmation, aspirin provocation testing provides critical insights into disease heterogeneity and phenotyping. Different challenge routes—nasal, bronchial, and oral—allow assessment of organ-specific sensitivity and inflammatory dominance. Nasal aspirin provocation primarily reflects upper airway involvement and is particularly informative in patients with severe CRSwNP, whereas inhalational lysine-aspirin challenges highlight lower-airway bronchial hyperresponsiveness. Oral aspirin provocation, through systemic exposure, captures the full spectrum of respiratory and extra-respiratory responses and therefore best reflects global disease severity. The pattern, timing, and intensity of reactions observed during provocation testing contribute to the identification of clinically relevant N-ERD subphenotypes, such as upper-airway-dominant disease, bronchial-predominant disease, or blended reactions involving both compartments. These phenotypic distinctions have direct therapeutic implications, influencing the selection of targeted treatments, including aspirin desensitization, biologic therapies, or surgical interventions. Moreover, provocation testing remains essential prior to aspirin desensitization to ensure both diagnostic accuracy and patient safety. Aspirin provocation tests are not merely confirmatory tools but represent a cornerstone of precision-based evaluation of N-ERD, enabling refined phenotyping, risk stratification, and individualized treatment planning in this complex and heterogeneous disease.
DOI: https://doi.org/10.37349/eaa.2026.1009121
This article belongs to the special issue Update on Chronic Rhinosinusitis
Phycocyanobilin (PCB), the covalently bound chromophore of the cyanobacterial protein C-phycocyanin (CPC), is recognized as a bioactive molecule with neuroprotective and anti-inflammatory properties. PCB and CPC, frequently coexisting in Spirulina extracts or experimental formulations, have demonstrated beneficial effects in preclinical models of multiple sclerosis, ischemic stroke, and Alzheimer’s disease. Reported mechanisms include attenuation of oxidative stress, reduction of neuroinflammation, and preservation of mitochondrial function, thereby contributing to a reparative microenvironment within the central nervous system. PCB can be obtained through two complementary approaches: Extraction from cyanobacterial biomass, where it remains covalently bound to CPC, and heterologous biosynthesis in Escherichia coli (E. coli), which enables production of free PCB as a high-purity, scalable linear tetrapyrrole suitable for translational applications. This mini-review summarizes current evidence on the neuroprotective actions of PCB and CPC, highlights their molecular targets, and discusses biotechnological advances that support their potential role in remyelination. By bridging natural pigment pharmacology with recombinant production strategies, PCB is positioned as a multitarget candidate of growing interest for the development of future neuroprotective and neurorepair therapies.
Phycocyanobilin (PCB), the covalently bound chromophore of the cyanobacterial protein C-phycocyanin (CPC), is recognized as a bioactive molecule with neuroprotective and anti-inflammatory properties. PCB and CPC, frequently coexisting in Spirulina extracts or experimental formulations, have demonstrated beneficial effects in preclinical models of multiple sclerosis, ischemic stroke, and Alzheimer’s disease. Reported mechanisms include attenuation of oxidative stress, reduction of neuroinflammation, and preservation of mitochondrial function, thereby contributing to a reparative microenvironment within the central nervous system. PCB can be obtained through two complementary approaches: Extraction from cyanobacterial biomass, where it remains covalently bound to CPC, and heterologous biosynthesis in Escherichia coli (E. coli), which enables production of free PCB as a high-purity, scalable linear tetrapyrrole suitable for translational applications. This mini-review summarizes current evidence on the neuroprotective actions of PCB and CPC, highlights their molecular targets, and discusses biotechnological advances that support their potential role in remyelination. By bridging natural pigment pharmacology with recombinant production strategies, PCB is positioned as a multitarget candidate of growing interest for the development of future neuroprotective and neurorepair therapies.
DOI: https://doi.org/10.37349/ent.2026.1004143
This article belongs to the special issue Natural Products in Neurotherapeutic Applications
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition typically requiring invasive endoscopy for monitoring. The bidirectional oral-gut axis suggests that saliva may serve as a non-invasive diagnostic fluid for studying gut inflammations. Studies of salivary biomarkers have shown varying results. Inflammatory biomarkers such as IL-6 are the most robust salivary biomarker, consistently correlating with endoscopic activity. In contrast, salivary calprotectin lacks the reliability of its fecal counterpart, showing diagnostic value primarily in pediatric cases with oral manifestations. Microbial analysis indicates reduced salivary diversity, specifically an enrichment of Prevotella and Veillonella alongside a depletion of core commensals like Streptococcus. While oxidative stress markers such as advanced oxidation protein products (AOPPs) can distinguish disease severity, they lack long-term prognostic utility. Conversely, recent shifts toward exosome-based transcriptomic analysis have improved the stability of salivary microRNAs, offering high precision in differentiating IBD phenotypes. Despite these advancements, clinical integration is currently hindered by small cohort sizes, the confounding effects of local oral health, and a lack of standardized collection protocols. To establish saliva as a reliable tool in the IBD clinical toolkit, future research must prioritize multi-panel biomarker approaches and longitudinal studies to validate diagnostic accuracy across diverse patient populations.
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition typically requiring invasive endoscopy for monitoring. The bidirectional oral-gut axis suggests that saliva may serve as a non-invasive diagnostic fluid for studying gut inflammations. Studies of salivary biomarkers have shown varying results. Inflammatory biomarkers such as IL-6 are the most robust salivary biomarker, consistently correlating with endoscopic activity. In contrast, salivary calprotectin lacks the reliability of its fecal counterpart, showing diagnostic value primarily in pediatric cases with oral manifestations. Microbial analysis indicates reduced salivary diversity, specifically an enrichment of Prevotella and Veillonella alongside a depletion of core commensals like Streptococcus. While oxidative stress markers such as advanced oxidation protein products (AOPPs) can distinguish disease severity, they lack long-term prognostic utility. Conversely, recent shifts toward exosome-based transcriptomic analysis have improved the stability of salivary microRNAs, offering high precision in differentiating IBD phenotypes. Despite these advancements, clinical integration is currently hindered by small cohort sizes, the confounding effects of local oral health, and a lack of standardized collection protocols. To establish saliva as a reliable tool in the IBD clinical toolkit, future research must prioritize multi-panel biomarker approaches and longitudinal studies to validate diagnostic accuracy across diverse patient populations.
DOI: https://doi.org/10.37349/edd.2026.1005117
