In biosensor technology, reliable attachment of protein-based probes requires careful control of the orientation of the probe molecule on the biosensor surface. In this regard, polyhistidine peptide became an attractive target for on surface immobilization. The present contribution details the total synthesis and the surface chemistry of a new antifouling organotrichlorosilane linker bearing a head function designed to immobilize the imidazole side chain of histidine for future immobilizations with polyhistidine peptide onto biosensor surface.
A novel organotrichlorosilane linker bearing the ethylene glycol backbone and a 2-chloroethyl sulfone head function (which can be converted to the vinyl sulfone group for subsequent attachment with imidazole) were synthesized via a multiple-step synthesis and carefully characterized. Surface modifications using the synthesized novel organotrichlorosilane linker, subsequent conversion to vinyl sulfone head function, and treatment with N-protected histidine were demonstrated on black lithium niobate substrate.
Novel organotrichlorosilane linker was successfully synthesized, though it was also observed that organotrichlorosilane linker was quite moisture reactive. Surface characterizations also indicated successful modification of lithium niobate with the novel organotrichlorosilane linker as well as presence of N-protected histidine on the lithium niobate surface post-immobilization.
A novel organotrichlorosilane linker bearing the 2-chloroethylsulfone group was successfully synthesized and successful immobilization with N-protected histidine was demonstrated. The surface chemistry demonstrated onto lithium niobate herein is immediately applicable for future on-surface immobilization of protein-based probe molecules bearing polyhistidine moieties.
In biosensor technology, reliable attachment of protein-based probes requires careful control of the orientation of the probe molecule on the biosensor surface. In this regard, polyhistidine peptide became an attractive target for on surface immobilization. The present contribution details the total synthesis and the surface chemistry of a new antifouling organotrichlorosilane linker bearing a head function designed to immobilize the imidazole side chain of histidine for future immobilizations with polyhistidine peptide onto biosensor surface.
A novel organotrichlorosilane linker bearing the ethylene glycol backbone and a 2-chloroethyl sulfone head function (which can be converted to the vinyl sulfone group for subsequent attachment with imidazole) were synthesized via a multiple-step synthesis and carefully characterized. Surface modifications using the synthesized novel organotrichlorosilane linker, subsequent conversion to vinyl sulfone head function, and treatment with N-protected histidine were demonstrated on black lithium niobate substrate.
Novel organotrichlorosilane linker was successfully synthesized, though it was also observed that organotrichlorosilane linker was quite moisture reactive. Surface characterizations also indicated successful modification of lithium niobate with the novel organotrichlorosilane linker as well as presence of N-protected histidine on the lithium niobate surface post-immobilization.
A novel organotrichlorosilane linker bearing the 2-chloroethylsulfone group was successfully synthesized and successful immobilization with N-protected histidine was demonstrated. The surface chemistry demonstrated onto lithium niobate herein is immediately applicable for future on-surface immobilization of protein-based probe molecules bearing polyhistidine moieties.
Establishing remission as a clinical goal for carefully selected patients with Type 2 Diabetes Mellitus (T2DM) represents a fundamental shift from the traditional paradigm of lifelong disease management. Short disease duration, preserved C-peptide levels, and overweight or obesity are the central criteria for T2DM remission. T2DM remission may help reduce the psychological burden on patients, improve quality of life, delay disease progression, and reduce the risk of long-term complications. This consensus aims to help physicians establish standardized clinical diagnosis and treatment protocols for T2DM remission in overweight or obese patients with T2DM, and support related research to develop safer and more effective interventions. Notably, T2DM remission is conditional, reversible and population-selective, which is not universally applicable to all T2DM patients across different disease stages and healthcare settings.
Establishing remission as a clinical goal for carefully selected patients with Type 2 Diabetes Mellitus (T2DM) represents a fundamental shift from the traditional paradigm of lifelong disease management. Short disease duration, preserved C-peptide levels, and overweight or obesity are the central criteria for T2DM remission. T2DM remission may help reduce the psychological burden on patients, improve quality of life, delay disease progression, and reduce the risk of long-term complications. This consensus aims to help physicians establish standardized clinical diagnosis and treatment protocols for T2DM remission in overweight or obese patients with T2DM, and support related research to develop safer and more effective interventions. Notably, T2DM remission is conditional, reversible and population-selective, which is not universally applicable to all T2DM patients across different disease stages and healthcare settings.
Edible insects are a sustainable food source, due to their high nutritional value and low environmental impact. This review explores how bioinformatics improves the nutritional value and farming efficiency of edible insects, focusing on Tenebrio molitor (mealworms), Hermetia illucens [black soldier fly larvae (BSFL)], and Acheta domesticus (crickets). These insects provide micronutrients like vitamin B12 and iron with 10% to 50% lipids and 30% to 70% protein. Bioinformatics is enhancing the breeding and sustainability of insects, which optimizes nutrient extraction through genomic and metabolomic analyses done by using tools like NCBI and KEGG. For commercial farming, A. domesticus and T. molitor are ideal, while BSFL are excellent in waste recycling. Unlike previous reviews centered primarily on compositional analysis, this review uniquely links genomic and metabolomic bioinformatics approaches with targeted nutritional optimization in edible insect production. Despite these advantages, challenges such as regulatory gaps, high computational costs, consumer demand in Western markets, and acceptance of insect produced products by consumers are still the challenges for their scalability. Insect farming by using bioinformatics reduces environmental impacts and offers a scalable, sustainable solution to global food security. Continued research into cost-effective computational methods and consumer acceptance strategies is essential to introduce insects into food systems. All the data present in review are broadly representative of edible insects, values fall within these intervals but vary according to feed substrate and production system.
Edible insects are a sustainable food source, due to their high nutritional value and low environmental impact. This review explores how bioinformatics improves the nutritional value and farming efficiency of edible insects, focusing on Tenebrio molitor (mealworms), Hermetia illucens [black soldier fly larvae (BSFL)], and Acheta domesticus (crickets). These insects provide micronutrients like vitamin B12 and iron with 10% to 50% lipids and 30% to 70% protein. Bioinformatics is enhancing the breeding and sustainability of insects, which optimizes nutrient extraction through genomic and metabolomic analyses done by using tools like NCBI and KEGG. For commercial farming, A. domesticus and T. molitor are ideal, while BSFL are excellent in waste recycling. Unlike previous reviews centered primarily on compositional analysis, this review uniquely links genomic and metabolomic bioinformatics approaches with targeted nutritional optimization in edible insect production. Despite these advantages, challenges such as regulatory gaps, high computational costs, consumer demand in Western markets, and acceptance of insect produced products by consumers are still the challenges for their scalability. Insect farming by using bioinformatics reduces environmental impacts and offers a scalable, sustainable solution to global food security. Continued research into cost-effective computational methods and consumer acceptance strategies is essential to introduce insects into food systems. All the data present in review are broadly representative of edible insects, values fall within these intervals but vary according to feed substrate and production system.
Although emotions play a fundamental role in modulating pain perception, their objective assessment in clinical contexts remains challenging. Recent advances in artificial intelligence (AI) have opened new opportunities to measure emotional states through facial expression analysis, physiological signal modeling, natural language processing (NLP), and multimodal data integration. In affective computing, the field that focuses on technologies designed to recognize, interpret, process, and simulate human emotions, facial expression-based emotion recognition has progressed from traditional machine learning methods to advanced deep learning approaches, including convolutional neural networks (CNNs), attention-based hybrid models, and transformer architectures. Similarly, recurrent neural networks and self-supervised learning methods have been implemented for developing models from physiological signals such as electrocardiography, photoplethysmography, galvanic skin response, and related biosignals. Additionally, NLP systems can extract affective information from naturalistic text, using both lexicon-based and transformer-based models. Finally, multimodal fusion and alignment techniques allow the integration of heterogeneous data streams, providing richer and more ecologically valid emotion representations. Collectively, these strategies offer powerful tools for advancing automatic pain assessment (APA) in cancer care, with the potential to support personalized, emotion-aware therapeutic approaches. However, from an AI perspective, several open challenges remain, including multimodal representation learning under weak supervision, robustness to missing or degraded modalities, limited explainability of affective inference models, lack of standardized benchmarking protocols, and the presence of bias and domain shift in emotion datasets. Given the inherently subjective, context-dependent, and culturally mediated features of the emotional experience, further research is needed to address these technical limitations, integrating technological advances with the intrinsic complexity of emotion interpretation.
Although emotions play a fundamental role in modulating pain perception, their objective assessment in clinical contexts remains challenging. Recent advances in artificial intelligence (AI) have opened new opportunities to measure emotional states through facial expression analysis, physiological signal modeling, natural language processing (NLP), and multimodal data integration. In affective computing, the field that focuses on technologies designed to recognize, interpret, process, and simulate human emotions, facial expression-based emotion recognition has progressed from traditional machine learning methods to advanced deep learning approaches, including convolutional neural networks (CNNs), attention-based hybrid models, and transformer architectures. Similarly, recurrent neural networks and self-supervised learning methods have been implemented for developing models from physiological signals such as electrocardiography, photoplethysmography, galvanic skin response, and related biosignals. Additionally, NLP systems can extract affective information from naturalistic text, using both lexicon-based and transformer-based models. Finally, multimodal fusion and alignment techniques allow the integration of heterogeneous data streams, providing richer and more ecologically valid emotion representations. Collectively, these strategies offer powerful tools for advancing automatic pain assessment (APA) in cancer care, with the potential to support personalized, emotion-aware therapeutic approaches. However, from an AI perspective, several open challenges remain, including multimodal representation learning under weak supervision, robustness to missing or degraded modalities, limited explainability of affective inference models, lack of standardized benchmarking protocols, and the presence of bias and domain shift in emotion datasets. Given the inherently subjective, context-dependent, and culturally mediated features of the emotional experience, further research is needed to address these technical limitations, integrating technological advances with the intrinsic complexity of emotion interpretation.
The NEUROD2 gene encodes a transcription factor essential for neuronal differentiation and cortical development. Pathogenic variants cause a rare autosomal dominant neurodevelopmental disorder with variable expressivity, typically presenting in early infancy with developmental delay, epilepsy, and behavioral abnormalities. We report a newborn girl carrying a de novo heterozygous missense variant NM_006160.4:c.790G>A, p.(Ala264Thr), located outside the canonical basic helix-loop-helix (bHLH) domain. Soon after birth, she presented respiratory depression, hypotonia, feeding difficulties, and electrographic seizures. Magnetic resonance imaging (MRI) showed subcortical white matter hyperintensity, and the electroencephalogram (EEG) revealed abnormal background activity. During follow-up, epilepsy was controlled, but neurodevelopmental delay with autistic features emerged. This case represents the earliest reported clinical onset associated with NEUROD2 variants and expands the phenotypic and mutational spectrum. It highlights that variants outside known hotspots can cause severe disease and supports including NEUROD2 in the differential diagnosis of neonatal neurological impairment.
The NEUROD2 gene encodes a transcription factor essential for neuronal differentiation and cortical development. Pathogenic variants cause a rare autosomal dominant neurodevelopmental disorder with variable expressivity, typically presenting in early infancy with developmental delay, epilepsy, and behavioral abnormalities. We report a newborn girl carrying a de novo heterozygous missense variant NM_006160.4:c.790G>A, p.(Ala264Thr), located outside the canonical basic helix-loop-helix (bHLH) domain. Soon after birth, she presented respiratory depression, hypotonia, feeding difficulties, and electrographic seizures. Magnetic resonance imaging (MRI) showed subcortical white matter hyperintensity, and the electroencephalogram (EEG) revealed abnormal background activity. During follow-up, epilepsy was controlled, but neurodevelopmental delay with autistic features emerged. This case represents the earliest reported clinical onset associated with NEUROD2 variants and expands the phenotypic and mutational spectrum. It highlights that variants outside known hotspots can cause severe disease and supports including NEUROD2 in the differential diagnosis of neonatal neurological impairment.
Antimicrobial resistance (AMR) poses a growing global health threat, progressively undermining the clinical effectiveness of conventional antibiotic therapies. Despite their proven efficacy and standardized clinical frameworks, antibiotics exert strong selective pressures that accelerate resistance, disrupt host microbiota, and limit treatment options for chronic, biofilm-associated, and multidrug-resistant infections. Bacteriophage therapy has re-emerged as a potential adjunct or alternative approach, offering pathogen-specific antibacterial activity, preservation of commensal microbiota, and the capacity for co-evolution with bacterial hosts. This focused review critically compares antibiotics and bacteriophage therapy across mechanistic foundations, preclinical and clinical evidence, translational readiness, and real-world implementation challenges. While preclinical models consistently demonstrate robust antibacterial activity of bacteriophages, clinical evidence remains heterogeneous, with few randomized controlled studies available. Key system-level barriers, including regulatory inconsistency, manufacturing complexity, and lack of standardization, currently limit widespread clinical integration. Rather than positioning bacteriophages as replacements for antibiotics, this review emphasizes their potential role as complementary agents, particularly through bacteriophage-antibiotic synergy, to enhance treatment efficacy and mitigate resistance. Addressing methodological gaps, standardizing clinical trial designs, and developing integrated stewardship models will be critical to defining the future role of bacteriophage therapy in modern infectious disease management.
Antimicrobial resistance (AMR) poses a growing global health threat, progressively undermining the clinical effectiveness of conventional antibiotic therapies. Despite their proven efficacy and standardized clinical frameworks, antibiotics exert strong selective pressures that accelerate resistance, disrupt host microbiota, and limit treatment options for chronic, biofilm-associated, and multidrug-resistant infections. Bacteriophage therapy has re-emerged as a potential adjunct or alternative approach, offering pathogen-specific antibacterial activity, preservation of commensal microbiota, and the capacity for co-evolution with bacterial hosts. This focused review critically compares antibiotics and bacteriophage therapy across mechanistic foundations, preclinical and clinical evidence, translational readiness, and real-world implementation challenges. While preclinical models consistently demonstrate robust antibacterial activity of bacteriophages, clinical evidence remains heterogeneous, with few randomized controlled studies available. Key system-level barriers, including regulatory inconsistency, manufacturing complexity, and lack of standardization, currently limit widespread clinical integration. Rather than positioning bacteriophages as replacements for antibiotics, this review emphasizes their potential role as complementary agents, particularly through bacteriophage-antibiotic synergy, to enhance treatment efficacy and mitigate resistance. Addressing methodological gaps, standardizing clinical trial designs, and developing integrated stewardship models will be critical to defining the future role of bacteriophage therapy in modern infectious disease management.
Green coffee processing, before the roasting phase, requires effective removal of foreign materials and defective kernels to ensure product quality, process safety, and compliance with industrial requirements. The aim of this research is to use conventional RGB-based optical sorters for product sorting. These rely primarily on surface colour characteristics and can be limited when contaminants display visual similarities to healthy beans.
Hyperspectral imaging (HSI) provides a non-destructive alternative by integrating spatial and spectral information in the visible and near-infrared (VIS/NIR) range. In this study, a VIS/NIR HSI system was integrated into a commercial industrial optical sorter and validated under real operating conditions. Contaminated green coffee batches (10 kg) containing known amounts of organic and inorganic contaminants were processed through multiple sorting passes using a statistical classification logic embedded into the sorter programmable logic controller (PLC) for real-time decision making.
The system achieved complete removal of stone contaminants after a single pass, while organic contaminants (peel and defective beans) were substantially reduced across successive cycles. After two sorting passes, the cumulative yield of compliant coffee beans was approximately 84%, representing an acceptable trade-off between contaminant removal efficiency and product loss in an industrial context.
Overall, the results support the feasibility of deploying VIS/NIR hyperspectral sensing for high-throughput industrial coffee sorting, with potential advantages in discrimination capability compared with conventional colour-based systems.
Green coffee processing, before the roasting phase, requires effective removal of foreign materials and defective kernels to ensure product quality, process safety, and compliance with industrial requirements. The aim of this research is to use conventional RGB-based optical sorters for product sorting. These rely primarily on surface colour characteristics and can be limited when contaminants display visual similarities to healthy beans.
Hyperspectral imaging (HSI) provides a non-destructive alternative by integrating spatial and spectral information in the visible and near-infrared (VIS/NIR) range. In this study, a VIS/NIR HSI system was integrated into a commercial industrial optical sorter and validated under real operating conditions. Contaminated green coffee batches (10 kg) containing known amounts of organic and inorganic contaminants were processed through multiple sorting passes using a statistical classification logic embedded into the sorter programmable logic controller (PLC) for real-time decision making.
The system achieved complete removal of stone contaminants after a single pass, while organic contaminants (peel and defective beans) were substantially reduced across successive cycles. After two sorting passes, the cumulative yield of compliant coffee beans was approximately 84%, representing an acceptable trade-off between contaminant removal efficiency and product loss in an industrial context.
Overall, the results support the feasibility of deploying VIS/NIR hyperspectral sensing for high-throughput industrial coffee sorting, with potential advantages in discrimination capability compared with conventional colour-based systems.
Alkylphenols (APs) are synthetic organic compounds widely used in the chemical industry and in consumer products such as detergents, cosmetics, plastics, pesticides, pharmaceuticals, and cleaning agents. These compounds are persistent in the environment, prone to bioaccumulation in aquatic organisms, and exhibit considerable toxicity. Their presence has been reported in a wide range of environmental matrices, including surface water, wastewater, drinking water, sediments, and biological tissues, with concentrations reaching up to 30 μg/L in surface waters. The aim of this work is to study the concentration of APs in drinking water samples from several locations across the Mediterranean basin of Spain in order to establish an assessment of the occurrence of these compounds in these samples.
In this study, a solid-phase extraction (SPE) method followed by gas chromatography-mass spectrometry (GC-MS) was developed, validated, and applied to determine the presence of APs in water. Two sorbents (C18 and HLB) were evaluated for extraction efficiency, with C18 yielding the best recoveries. The method showed good linearity and low detection and quantification limits, achieving acceptable recovery and precision values across various concentrations.
A set of 64 tap water samples was collected across Spain between February and May 2025, and 4-nonylphenol (4-NP), 4-octylphenol (4-OP), and 4-tert-octylphenol (4-tOP) concentrations were determined. Among the compounds studied, 4-OP was the most frequently detected (73%), followed by 4-NP (34%) and 4-tOP (12%). All detected concentrations were below the legal threshold of 0.3 µg/L, although certain locations showed relatively higher levels.
The results demonstrate the method’s suitability for environmental monitoring and highlight the continued presence of APs in drinking water despite existing regulations, with the 4-alkylphenol (4-AP) being the most prevalent found in the analyzed drinking water.
Alkylphenols (APs) are synthetic organic compounds widely used in the chemical industry and in consumer products such as detergents, cosmetics, plastics, pesticides, pharmaceuticals, and cleaning agents. These compounds are persistent in the environment, prone to bioaccumulation in aquatic organisms, and exhibit considerable toxicity. Their presence has been reported in a wide range of environmental matrices, including surface water, wastewater, drinking water, sediments, and biological tissues, with concentrations reaching up to 30 μg/L in surface waters. The aim of this work is to study the concentration of APs in drinking water samples from several locations across the Mediterranean basin of Spain in order to establish an assessment of the occurrence of these compounds in these samples.
In this study, a solid-phase extraction (SPE) method followed by gas chromatography-mass spectrometry (GC-MS) was developed, validated, and applied to determine the presence of APs in water. Two sorbents (C18 and HLB) were evaluated for extraction efficiency, with C18 yielding the best recoveries. The method showed good linearity and low detection and quantification limits, achieving acceptable recovery and precision values across various concentrations.
A set of 64 tap water samples was collected across Spain between February and May 2025, and 4-nonylphenol (4-NP), 4-octylphenol (4-OP), and 4-tert-octylphenol (4-tOP) concentrations were determined. Among the compounds studied, 4-OP was the most frequently detected (73%), followed by 4-NP (34%) and 4-tOP (12%). All detected concentrations were below the legal threshold of 0.3 µg/L, although certain locations showed relatively higher levels.
The results demonstrate the method’s suitability for environmental monitoring and highlight the continued presence of APs in drinking water despite existing regulations, with the 4-alkylphenol (4-AP) being the most prevalent found in the analyzed drinking water.
This study aimed to investigate the fruit of Berberis asiatica as a potential source of bioactive anthocyanins and to evaluate their antioxidant and antimicrobial properties with insights into molecular docking studies.
Crude extracts were prepared using solvents of varying polarity and characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Fourier-transform infrared spectroscopy (FT-IR) analyses. The total anthocyanin content was quantified, and antioxidant activity was assessed using the DPPH radical scavenging assay and total antioxidant capacity. Antimicrobial activity was evaluated against selected bacterial and fungal strains. Additionally, in silico molecular docking studies were performed to examine ligand-target interactions.
LC-MS/MS analysis identified eight compounds, including cyanidin-3-O-glucoside, cyanidin-3,5-diglucoside, malvidin-3-O-arabinoside, pelargonidin-3-O-glucoside, peonidin-3-O-glucoside, petunidin-3-O-glucoside, catechin, and epicatechin, indicating a pigment profile dominated by mono- and diglycosylated anthocyanins. The total anthocyanin content was 128.72 mg/g dry fruit, exceeding previously reported values for related species. Methanolic (80% v/v) and hydroalcoholic (50% v/v) extracts showed strong antioxidant activity (DPPH IC50 = 10.13 and 12.56 µg/mL, respectively), whereas nonpolar fractions were less active. At 200 µg/mL, these extracts exhibited significant antimicrobial activity, with inhibition zones up to 42 mm against Escherichia coli and 41 mm against Micrococcus luteus, along with antifungal effects against Aspergillus niger and Candida albicans. Docking studies revealed favorable binding energies (–7.3 to –8.0 kcal/mol) for key compounds against selected microbial and enzymatic targets.
The findings demonstrate that Berberis asiatica fruit is a rich source of anthocyanin-based pigments with potent antioxidant and antimicrobial activities. These results highlight its potential as a sustainable source of multifunctional bioactive compounds for nutraceutical and therapeutic applications.
This study aimed to investigate the fruit of Berberis asiatica as a potential source of bioactive anthocyanins and to evaluate their antioxidant and antimicrobial properties with insights into molecular docking studies.
Crude extracts were prepared using solvents of varying polarity and characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Fourier-transform infrared spectroscopy (FT-IR) analyses. The total anthocyanin content was quantified, and antioxidant activity was assessed using the DPPH radical scavenging assay and total antioxidant capacity. Antimicrobial activity was evaluated against selected bacterial and fungal strains. Additionally, in silico molecular docking studies were performed to examine ligand-target interactions.
LC-MS/MS analysis identified eight compounds, including cyanidin-3-O-glucoside, cyanidin-3,5-diglucoside, malvidin-3-O-arabinoside, pelargonidin-3-O-glucoside, peonidin-3-O-glucoside, petunidin-3-O-glucoside, catechin, and epicatechin, indicating a pigment profile dominated by mono- and diglycosylated anthocyanins. The total anthocyanin content was 128.72 mg/g dry fruit, exceeding previously reported values for related species. Methanolic (80% v/v) and hydroalcoholic (50% v/v) extracts showed strong antioxidant activity (DPPH IC50 = 10.13 and 12.56 µg/mL, respectively), whereas nonpolar fractions were less active. At 200 µg/mL, these extracts exhibited significant antimicrobial activity, with inhibition zones up to 42 mm against Escherichia coli and 41 mm against Micrococcus luteus, along with antifungal effects against Aspergillus niger and Candida albicans. Docking studies revealed favorable binding energies (–7.3 to –8.0 kcal/mol) for key compounds against selected microbial and enzymatic targets.
The findings demonstrate that Berberis asiatica fruit is a rich source of anthocyanin-based pigments with potent antioxidant and antimicrobial activities. These results highlight its potential as a sustainable source of multifunctional bioactive compounds for nutraceutical and therapeutic applications.
Myxofibrosarcoma (MFS) is characterized by high local recurrence and complex microenvironmental interactions. Although three-dimensional (3D) culture systems better mimic in vivo tumor architecture than conventional two-dimensional (2D) monolayer cultures, the global proteomic consequences of dimensionality in MFS remain incompletely defined.
We performed quantitative mass spectrometry-based proteomic profiling of eight independently established patient-derived MFS cell lines cultured under 2D monolayer and 3D spheroid conditions. Differential protein expression and pathway enrichment analyses were conducted to delineate dimensionality-driven molecular programs.
Culture dimensionality emerged as the principal determinant of proteomic variation across all cell lines. Compared with monolayers, 3D spheroids exhibited significant enrichment of hypoxia response, autophagy-related processes, extracellular matrix organization, and PI3K-Akt signaling pathways. In contrast, 2D cultures preferentially upregulated DNA replication, RNA processing, and cell-cycle-associated pathways. These findings indicate that 3D architecture alone is sufficient to induce coordinated stress-adaptive and survival-oriented proteomic reprogramming in MFS cells.
This study provides a comprehensive proteomic atlas defining dimensionality-dependent molecular states in MFS. While functional validation was beyond the scope of this work, the pathway rewiring identified here establishes a mechanistic framework for future hypothesis-driven investigations targeting autophagy- and PI3K-Akt-associated vulnerabilities in 3D MFS models.
Myxofibrosarcoma (MFS) is characterized by high local recurrence and complex microenvironmental interactions. Although three-dimensional (3D) culture systems better mimic in vivo tumor architecture than conventional two-dimensional (2D) monolayer cultures, the global proteomic consequences of dimensionality in MFS remain incompletely defined.
We performed quantitative mass spectrometry-based proteomic profiling of eight independently established patient-derived MFS cell lines cultured under 2D monolayer and 3D spheroid conditions. Differential protein expression and pathway enrichment analyses were conducted to delineate dimensionality-driven molecular programs.
Culture dimensionality emerged as the principal determinant of proteomic variation across all cell lines. Compared with monolayers, 3D spheroids exhibited significant enrichment of hypoxia response, autophagy-related processes, extracellular matrix organization, and PI3K-Akt signaling pathways. In contrast, 2D cultures preferentially upregulated DNA replication, RNA processing, and cell-cycle-associated pathways. These findings indicate that 3D architecture alone is sufficient to induce coordinated stress-adaptive and survival-oriented proteomic reprogramming in MFS cells.
This study provides a comprehensive proteomic atlas defining dimensionality-dependent molecular states in MFS. While functional validation was beyond the scope of this work, the pathway rewiring identified here establishes a mechanistic framework for future hypothesis-driven investigations targeting autophagy- and PI3K-Akt-associated vulnerabilities in 3D MFS models.
This study aimed to assess the prevalence and patterns of aeroallergen sensitisation in steroid-naïve, newly diagnosed adult patients with bronchial asthma using skin prick test (SPT), and to examine its association with lung function parameters measured by oscillometry and spirometry.
Consecutive adult patients with bronchial asthma who were naïve to systemic and inhaled corticosteroids were recruited. Following a detailed clinical history and blood investigations, lung function was assessed using oscillometry and spirometry. SPT was performed using a panel of 13 aeroallergens in accordance with established guidelines. Based on SPT results, patients were stratified into two groups: atopic asthma (sensitisation to ≥ 1 allergen) and non-atopic asthma (no sensitisation). Demographic characteristics, blood parameters, and lung function parameters were compared between the two groups.
Of 257 patients screened, 205 were enrolled (59% men; mean age 36.9 years). Allergic rhinitis was present in 58% of patients, and 69.8% had atopic asthma (95% CI 62.9–75.6). Sensitisation was most common to house dust mites (47.8%), followed by cockroach (37.6%) and weed pollen (29.8%). Atopy was more prevalent in men than in women and was associated with higher serum total IgE levels. Peripheral blood eosinophil counts, oscillometric parameters, severity of airflow obstruction, and bronchodilator responses did not differ significantly between atopic and non-atopic patients.
The majority of asthma patients exhibited sensitisation to one or more aeroallergens. Despite differences in immunopathogenesis, no significant differences in oscillometric parameters were observed between atopic and non-atopic asthma, suggesting that atopic status has a limited influence on the severity of small airway dysfunction.
This study aimed to assess the prevalence and patterns of aeroallergen sensitisation in steroid-naïve, newly diagnosed adult patients with bronchial asthma using skin prick test (SPT), and to examine its association with lung function parameters measured by oscillometry and spirometry.
Consecutive adult patients with bronchial asthma who were naïve to systemic and inhaled corticosteroids were recruited. Following a detailed clinical history and blood investigations, lung function was assessed using oscillometry and spirometry. SPT was performed using a panel of 13 aeroallergens in accordance with established guidelines. Based on SPT results, patients were stratified into two groups: atopic asthma (sensitisation to ≥ 1 allergen) and non-atopic asthma (no sensitisation). Demographic characteristics, blood parameters, and lung function parameters were compared between the two groups.
Of 257 patients screened, 205 were enrolled (59% men; mean age 36.9 years). Allergic rhinitis was present in 58% of patients, and 69.8% had atopic asthma (95% CI 62.9–75.6). Sensitisation was most common to house dust mites (47.8%), followed by cockroach (37.6%) and weed pollen (29.8%). Atopy was more prevalent in men than in women and was associated with higher serum total IgE levels. Peripheral blood eosinophil counts, oscillometric parameters, severity of airflow obstruction, and bronchodilator responses did not differ significantly between atopic and non-atopic patients.
The majority of asthma patients exhibited sensitisation to one or more aeroallergens. Despite differences in immunopathogenesis, no significant differences in oscillometric parameters were observed between atopic and non-atopic asthma, suggesting that atopic status has a limited influence on the severity of small airway dysfunction.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. Consequently, standard hormone and HER2-targeted therapies are ineffective, necessitating reliance on chemotherapy, immunotherapy, antibody-drug conjugates (ADCs), and poly(ADP-ribose) polymerase (PARP) inhibitors for BRCA-mutated cases. TNBC exhibits rapid growth, a high risk of early recurrence, and disproportionately affects younger women, Black women, and BRCA1 mutation carriers. Standard management typically involves neoadjuvant chemotherapy followed by surgery and potential radiation. However, TNBC treatment remains challenging due to its severe biological heterogeneity, high metastatic potential, and the toxicity associated with systemic therapies. This review discusses the current understanding of TNBC biology, highlighting the urgent need for advanced diagnostics, integrated molecular subtyping, and personalized targeted therapies.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. Consequently, standard hormone and HER2-targeted therapies are ineffective, necessitating reliance on chemotherapy, immunotherapy, antibody-drug conjugates (ADCs), and poly(ADP-ribose) polymerase (PARP) inhibitors for BRCA-mutated cases. TNBC exhibits rapid growth, a high risk of early recurrence, and disproportionately affects younger women, Black women, and BRCA1 mutation carriers. Standard management typically involves neoadjuvant chemotherapy followed by surgery and potential radiation. However, TNBC treatment remains challenging due to its severe biological heterogeneity, high metastatic potential, and the toxicity associated with systemic therapies. This review discusses the current understanding of TNBC biology, highlighting the urgent need for advanced diagnostics, integrated molecular subtyping, and personalized targeted therapies.
Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention for its neuroprotective properties, especially for Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder with limited therapeutic options. This review provides several experimental evidence on the effects of TQ in AD models. The evidences indicate that TQ reduces the amyloid-β accumulation, reduces the oxidative stress and neuroinflammation, and improves cognitive and behavioral outcomes. Additionally, TQ should be able to promote the neuronal survival and neurogenesis while reducing biological markers that indicate brain damage or neuron loss. Although these findings clearly highlight and show the promising therapeutic potential of the TQ molecule in the AD, it is important to note that further in-depth studies are still needed to fully understand its underlying molecular mechanisms and to determine its clinical relevance in patients.
Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention for its neuroprotective properties, especially for Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder with limited therapeutic options. This review provides several experimental evidence on the effects of TQ in AD models. The evidences indicate that TQ reduces the amyloid-β accumulation, reduces the oxidative stress and neuroinflammation, and improves cognitive and behavioral outcomes. Additionally, TQ should be able to promote the neuronal survival and neurogenesis while reducing biological markers that indicate brain damage or neuron loss. Although these findings clearly highlight and show the promising therapeutic potential of the TQ molecule in the AD, it is important to note that further in-depth studies are still needed to fully understand its underlying molecular mechanisms and to determine its clinical relevance in patients.
The emerging field of immunometabolism has established that the metabolic pathways governing immune cell function—glycolysis, oxidative phosphorylation, fatty acid oxidation, and amino acid metabolism—are fundamental determinants of immune responses in health and disease. This review synthesizes current evidence on how dietary inputs serve as primary environmental modulators of this immunometabolism programming. We detail the mechanisms by which macronutrients (carbohydrates, lipids, proteins), micronutrients, and specific dietary patterns (e.g., Western, Mediterranean, ketogenic) engage key nutrient-sensing pathways (mechanistic target of rapamycin [mTOR], AMP-activated protein kinase [AMPK], hypoxia-inducible factor-1α [HIF-1α], peroxisome proliferator-activated receptor [PPARs]) to rewire immune cell metabolism and influence functional phenotypes. A central role is afforded to the gut microbiota as a critical intermediary, translating diet into immunoregulatory signals, such as short-chain fatty acids. We further explore how obesogenic diets disrupt this network to fuel chronic low-grade inflammation (metaflammation), driving the pathophysiology of common metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis. Finally, we evaluate therapeutic nutritional strategies—from nutraceuticals and probiotics to the promise of precision nutrition—designed to recalibrate immunometabolism. This review underscores that diet is a powerful, modifiable lever of immunity, positioning targeted nutritional intervention as a pivotal strategy for preventing and managing metabolic disease.
The emerging field of immunometabolism has established that the metabolic pathways governing immune cell function—glycolysis, oxidative phosphorylation, fatty acid oxidation, and amino acid metabolism—are fundamental determinants of immune responses in health and disease. This review synthesizes current evidence on how dietary inputs serve as primary environmental modulators of this immunometabolism programming. We detail the mechanisms by which macronutrients (carbohydrates, lipids, proteins), micronutrients, and specific dietary patterns (e.g., Western, Mediterranean, ketogenic) engage key nutrient-sensing pathways (mechanistic target of rapamycin [mTOR], AMP-activated protein kinase [AMPK], hypoxia-inducible factor-1α [HIF-1α], peroxisome proliferator-activated receptor [PPARs]) to rewire immune cell metabolism and influence functional phenotypes. A central role is afforded to the gut microbiota as a critical intermediary, translating diet into immunoregulatory signals, such as short-chain fatty acids. We further explore how obesogenic diets disrupt this network to fuel chronic low-grade inflammation (metaflammation), driving the pathophysiology of common metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis. Finally, we evaluate therapeutic nutritional strategies—from nutraceuticals and probiotics to the promise of precision nutrition—designed to recalibrate immunometabolism. This review underscores that diet is a powerful, modifiable lever of immunity, positioning targeted nutritional intervention as a pivotal strategy for preventing and managing metabolic disease.
This study aimed to evaluate the effect of incorporating aqueous extracts from Aloysia citrodora (lemon verbena) leaves and Pelargonium × hortorum (geranium) red flowers into semi-sweet biscuits in order to enhance antioxidant capacity and support the development of functional bakery products.
Aqueous extracts were incorporated into a standard biscuit formulation at two inclusion levels (10% and 30%). Dough and baked biscuits were analyzed for texture, colour, total phenolic content, and antioxidant capacity. The influence of extract type, concentration, and baking temperature (130°C and 160°C) on technological properties and bioactivity was assessed.
The low pH of the geranium extract (pH < 4) resulted in significantly softer dough textures (P < 0.05). Biscuit fracture stress did not differ among formulations (P > 0.05), indicating no adverse effects on structural integrity. Baking at 160°C produced crisper biscuits, particularly in control samples and those containing 30% lemon verbena, as indicated by higher Young’s modulus and lower fracture strain values. Antioxidant capacity was strongly dependent on extract type and concentration. Biscuits and doughs containing 30% geranium extract exhibited the highest antioxidant values (P < 0.05), while samples with 10% lemon verbena extract did not differ significantly from controls.
Pelargonium × hortorum red flower extract demonstrated strong potential as a natural antioxidant ingredient in bakery products, enabling the production of functional biscuits without compromising technological quality and supporting strategies aimed at reducing oxidative stress.
This study aimed to evaluate the effect of incorporating aqueous extracts from Aloysia citrodora (lemon verbena) leaves and Pelargonium × hortorum (geranium) red flowers into semi-sweet biscuits in order to enhance antioxidant capacity and support the development of functional bakery products.
Aqueous extracts were incorporated into a standard biscuit formulation at two inclusion levels (10% and 30%). Dough and baked biscuits were analyzed for texture, colour, total phenolic content, and antioxidant capacity. The influence of extract type, concentration, and baking temperature (130°C and 160°C) on technological properties and bioactivity was assessed.
The low pH of the geranium extract (pH < 4) resulted in significantly softer dough textures (P < 0.05). Biscuit fracture stress did not differ among formulations (P > 0.05), indicating no adverse effects on structural integrity. Baking at 160°C produced crisper biscuits, particularly in control samples and those containing 30% lemon verbena, as indicated by higher Young’s modulus and lower fracture strain values. Antioxidant capacity was strongly dependent on extract type and concentration. Biscuits and doughs containing 30% geranium extract exhibited the highest antioxidant values (P < 0.05), while samples with 10% lemon verbena extract did not differ significantly from controls.
Pelargonium × hortorum red flower extract demonstrated strong potential as a natural antioxidant ingredient in bakery products, enabling the production of functional biscuits without compromising technological quality and supporting strategies aimed at reducing oxidative stress.
The aim of this study is to investigate the molecular and functional features underlying the clinical heterogeneity between oligometastatic (OM) and polymetastatic (PM) colon cancer.
We performed a genotype-phenotype analysis in a homogeneous cohort of 127 patients with metastatic colon cancer (mCC) profiled using the same next-generation sequencing platform (TruSight Oncology® 500). OM disease was defined as the presence of one to three metastatic lesions per involved organ, involving no more than two organs overall, with all lesions measuring < 70 mm in maximum diameter and no single lesion > 25 mm. Molecular alterations, microsatellite instability (MSI), tumor mutational burden (TMB), and overall survival (OS) were analyzed. Gene Ontology (GO) enrichment and Phenolyzer network analyses were applied to explore functional differences between prognostically distinct molecular subgroups.
OM patients showed a striking survival advantage compared with PM patients [median OS not reached versus 29 months; hazard ratio (HR): 0.20, P < 0.0001], validating the clinical distinction between the two phenotypes. PM disease was significantly enriched for RAS mutations, whereas OM disease was associated with MSI-high status and elevated TMB. Canonical driver alterations were largely shared between groups, and Phenolyzer analysis revealed similar core oncogenic networks centered on adenomatous polyposis coli (APC), tumor protein p53 (TP53), and epidermal growth factor receptor (EGFR). In contrast, GO analysis demonstrated selective enrichment in PM tumors for molecular functions related to ATP binding, nucleotide binding, and protein kinase activity, consistent with enhanced bioenergetic demand and signaling intensity.
These findings support refined biological stratification of mCC and the exploration of personalized, metastasis-directed strategies, potentially incorporating immunological modulation in OM disease.
The aim of this study is to investigate the molecular and functional features underlying the clinical heterogeneity between oligometastatic (OM) and polymetastatic (PM) colon cancer.
We performed a genotype-phenotype analysis in a homogeneous cohort of 127 patients with metastatic colon cancer (mCC) profiled using the same next-generation sequencing platform (TruSight Oncology® 500). OM disease was defined as the presence of one to three metastatic lesions per involved organ, involving no more than two organs overall, with all lesions measuring < 70 mm in maximum diameter and no single lesion > 25 mm. Molecular alterations, microsatellite instability (MSI), tumor mutational burden (TMB), and overall survival (OS) were analyzed. Gene Ontology (GO) enrichment and Phenolyzer network analyses were applied to explore functional differences between prognostically distinct molecular subgroups.
OM patients showed a striking survival advantage compared with PM patients [median OS not reached versus 29 months; hazard ratio (HR): 0.20, P < 0.0001], validating the clinical distinction between the two phenotypes. PM disease was significantly enriched for RAS mutations, whereas OM disease was associated with MSI-high status and elevated TMB. Canonical driver alterations were largely shared between groups, and Phenolyzer analysis revealed similar core oncogenic networks centered on adenomatous polyposis coli (APC), tumor protein p53 (TP53), and epidermal growth factor receptor (EGFR). In contrast, GO analysis demonstrated selective enrichment in PM tumors for molecular functions related to ATP binding, nucleotide binding, and protein kinase activity, consistent with enhanced bioenergetic demand and signaling intensity.
These findings support refined biological stratification of mCC and the exploration of personalized, metastasis-directed strategies, potentially incorporating immunological modulation in OM disease.
By individual examination, the present review provides an overview of the potential involvement of various human microbiomes, including the gut, oral, skin, and nasal, in the pathophysiology of neurodegenerative diseases. Research has demonstrated that gut microbiome dysbiosis is linked to the pathogenesis of neurodegenerative conditions, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, through mechanisms involving microbial metabolites, neuroinflammation, amyloid aggregation, and altered neurotransmission. Emerging evidence suggests that the oral, skin, and nasal microbiomes may also influence neurodegenerative diseases through mechanisms such as microbial translocation, immune modulation, metabolite production, and interactions with the gut-brain axis. Although the potential of microbiome-based interventions for neurodegenerative diseases has been highlighted, several gaps remain, such as variability between human and animal models, a lack of standardized multi-omics approaches, and a limited understanding of individual microbial roles. Future studies should focus on clarifying the mechanisms by which dysbiosis in human host microbiomes impacts the pathophysiology of neurodegenerative diseases, identifying reliable biomarkers, and developing safe and effective microbiome-based therapies.
By individual examination, the present review provides an overview of the potential involvement of various human microbiomes, including the gut, oral, skin, and nasal, in the pathophysiology of neurodegenerative diseases. Research has demonstrated that gut microbiome dysbiosis is linked to the pathogenesis of neurodegenerative conditions, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, through mechanisms involving microbial metabolites, neuroinflammation, amyloid aggregation, and altered neurotransmission. Emerging evidence suggests that the oral, skin, and nasal microbiomes may also influence neurodegenerative diseases through mechanisms such as microbial translocation, immune modulation, metabolite production, and interactions with the gut-brain axis. Although the potential of microbiome-based interventions for neurodegenerative diseases has been highlighted, several gaps remain, such as variability between human and animal models, a lack of standardized multi-omics approaches, and a limited understanding of individual microbial roles. Future studies should focus on clarifying the mechanisms by which dysbiosis in human host microbiomes impacts the pathophysiology of neurodegenerative diseases, identifying reliable biomarkers, and developing safe and effective microbiome-based therapies.
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
Metabolic diseases, including obesity, insulin resistance, and type 2 diabetes mellitus, are increasingly recognized as conditions characterized by chronic low-grade inflammation driven by dysregulated cytokine signaling. Persistent elevation of pro-inflammatory mediators disrupts insulin signaling and contributes to metabolic dysfunction. Nutritional interventions capable of restoring cytokine balance are emerging as promising adjunct strategies for metabolic disease management. Chickpea (Cicer arietinum L.), a widely consumed legume, is rich in polyphenols, saponins, dietary fiber, and bioactive peptides with potential immunometabolic benefits. This review critically summarizes the role of chickpea bioactives in modulating cytokine signaling networks, with particular emphasis on the IL-6-JAK-STAT3-SOCS3 axis and NF-κB pathway. Chickpea components exert antioxidant and anti-inflammatory effects, suppress pro-inflammatory cytokine production, and may improve insulin sensitivity. Additionally, their potential chemoprotective effects in obesity-associated metabolic disorders are discussed. Furthermore, this review highlights key gaps in mechanistic and translational research and proposes future directions for pathway-oriented investigations. Although current evidence supports the therapeutic potential of chickpea, further mechanistic and clinical validation is required.
Metabolic diseases, including obesity, insulin resistance, and type 2 diabetes mellitus, are increasingly recognized as conditions characterized by chronic low-grade inflammation driven by dysregulated cytokine signaling. Persistent elevation of pro-inflammatory mediators disrupts insulin signaling and contributes to metabolic dysfunction. Nutritional interventions capable of restoring cytokine balance are emerging as promising adjunct strategies for metabolic disease management. Chickpea (Cicer arietinum L.), a widely consumed legume, is rich in polyphenols, saponins, dietary fiber, and bioactive peptides with potential immunometabolic benefits. This review critically summarizes the role of chickpea bioactives in modulating cytokine signaling networks, with particular emphasis on the IL-6-JAK-STAT3-SOCS3 axis and NF-κB pathway. Chickpea components exert antioxidant and anti-inflammatory effects, suppress pro-inflammatory cytokine production, and may improve insulin sensitivity. Additionally, their potential chemoprotective effects in obesity-associated metabolic disorders are discussed. Furthermore, this review highlights key gaps in mechanistic and translational research and proposes future directions for pathway-oriented investigations. Although current evidence supports the therapeutic potential of chickpea, further mechanistic and clinical validation is required.
Cardiopulmonary interaction is a fundamental physiological process during spontaneous breathing, but it is profoundly altered in critically ill patients receiving mechanical ventilation (MV). Positive-pressure ventilation modifies intrathoracic, pleural, and transpulmonary pressures, with major effects on pulmonary vascular hemodynamics and right ventricular performance. Among these consequences, acute pulmonary hypertension (aPH) has emerged as a clinically relevant yet frequently underrecognized complication. This review summarizes the current evidence on cardiopulmonary interaction during spontaneous breathing and MV, with particular emphasis on the mechanisms driving aPH and right ventricular dysfunction in critically ill patients. A narrative review was performed using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. Free-text terms and controlled vocabulary related to positive-pressure ventilation, right ventricular dysfunction, pulmonary hypertension (PH), pulmonary vascular resistance (PVR), right heart catheterization, intensive care, and respiratory compliance were combined using Boolean operators. Priority was given to studies involving adult patients, including systematic reviews, observational studies, clinical trials, and relevant reference lists. During spontaneous breathing, cardiopulmonary interaction is governed by negative intrathoracic pressure, venous return (VR), transpulmonary pressure, and physiological ventilation-perfusion relationships. In contrast, MV reverses this physiological pressure profile and may reduce VR, increase right ventricular afterload, impair ventricular interdependence, and increase PVR. High tidal volumes, excessive positive end-expiratory pressure, increased plateau pressure, hypercapnia, hypoxemia, alveolar overdistension, and diffuse lung injury all contribute to aPH, potentially disrupting right ventricle-pulmonary artery coupling and promoting right ventricular dysfunction. MV profoundly reshapes cardiopulmonary physiology and may precipitate aPH and right ventricular dysfunction. Early recognition of these mechanisms and the application of protective ventilatory strategies are essential to reduce pulmonary and hemodynamic complications.
Cardiopulmonary interaction is a fundamental physiological process during spontaneous breathing, but it is profoundly altered in critically ill patients receiving mechanical ventilation (MV). Positive-pressure ventilation modifies intrathoracic, pleural, and transpulmonary pressures, with major effects on pulmonary vascular hemodynamics and right ventricular performance. Among these consequences, acute pulmonary hypertension (aPH) has emerged as a clinically relevant yet frequently underrecognized complication. This review summarizes the current evidence on cardiopulmonary interaction during spontaneous breathing and MV, with particular emphasis on the mechanisms driving aPH and right ventricular dysfunction in critically ill patients. A narrative review was performed using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. Free-text terms and controlled vocabulary related to positive-pressure ventilation, right ventricular dysfunction, pulmonary hypertension (PH), pulmonary vascular resistance (PVR), right heart catheterization, intensive care, and respiratory compliance were combined using Boolean operators. Priority was given to studies involving adult patients, including systematic reviews, observational studies, clinical trials, and relevant reference lists. During spontaneous breathing, cardiopulmonary interaction is governed by negative intrathoracic pressure, venous return (VR), transpulmonary pressure, and physiological ventilation-perfusion relationships. In contrast, MV reverses this physiological pressure profile and may reduce VR, increase right ventricular afterload, impair ventricular interdependence, and increase PVR. High tidal volumes, excessive positive end-expiratory pressure, increased plateau pressure, hypercapnia, hypoxemia, alveolar overdistension, and diffuse lung injury all contribute to aPH, potentially disrupting right ventricle-pulmonary artery coupling and promoting right ventricular dysfunction. MV profoundly reshapes cardiopulmonary physiology and may precipitate aPH and right ventricular dysfunction. Early recognition of these mechanisms and the application of protective ventilatory strategies are essential to reduce pulmonary and hemodynamic complications.
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