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Neurodegenerative diseases are a complex ensemble of ailments characterized by progressive neuronal deterioration and ultimate loss, resulting in drastic impairments of memory, cognition and other brain functions. These incapacitating conditions are challenging for the public health system worldwide, with unfortunately no real cure and lack of efficient drugs capable of delaying or reversing these diseases. In this context, the endocannabinoid system and exogenous cannabinoids represent an interesting field of research due to numerous studies highlighting the neuroprotective effect of cannabinoids from different sources, i.e., endogenous, phytocannabinoids, and synthetic cannabinoids. This review highlights the multilayered effects of cannabinoids and the endocannabinoid system to block the progression of neurodegeneration and minimize the deleterious effects of insults that affect the brain. We illustrate examples showing that the main effects of cannabinoids modulate different components of the brain response to these insults at the level of three major mechanisms involved in neurodegeneration: neuroinflammation, excitotoxicity, and oxidative stress.
Neurodegenerative diseases are a complex ensemble of ailments characterized by progressive neuronal deterioration and ultimate loss, resulting in drastic impairments of memory, cognition and other brain functions. These incapacitating conditions are challenging for the public health system worldwide, with unfortunately no real cure and lack of efficient drugs capable of delaying or reversing these diseases. In this context, the endocannabinoid system and exogenous cannabinoids represent an interesting field of research due to numerous studies highlighting the neuroprotective effect of cannabinoids from different sources, i.e., endogenous, phytocannabinoids, and synthetic cannabinoids. This review highlights the multilayered effects of cannabinoids and the endocannabinoid system to block the progression of neurodegeneration and minimize the deleterious effects of insults that affect the brain. We illustrate examples showing that the main effects of cannabinoids modulate different components of the brain response to these insults at the level of three major mechanisms involved in neurodegeneration: neuroinflammation, excitotoxicity, and oxidative stress.
DOI: https://doi.org/10.37349/ent.2025.100498
This article belongs to the special issue GPCR Heteroreceptor Complexes as Key Players in Neuroprotection
Telemedicine (TM) is rapidly gaining recognition as a valuable tool for accessing medical treatments globally. The article aimed to review the latest literature on the role of TM in asthma care. It has been shown that TM offers numerous advantages for patients and clinicians, facilitating an easier access to healthcare resulting in higher patient satisfaction. Telemedicine technology, pushed by the COVID-19 pandemic, has improved asthma management, notably treatment adherence. Smart inhalers, wearable gadgets, and smartphone apps allow doctors to make data-driven decisions and empower patients to manage their diseases. Real-world research shows that TM is effective and patient-friendly. Infrastructure constraints, data security issues, and long-term patient engagement must be addressed. In conclusion, a hybrid strategy combining TM and in-person visits, enabled by AI and secure digital solutions, can provide equal, efficient, and comprehensive asthma management.
Telemedicine (TM) is rapidly gaining recognition as a valuable tool for accessing medical treatments globally. The article aimed to review the latest literature on the role of TM in asthma care. It has been shown that TM offers numerous advantages for patients and clinicians, facilitating an easier access to healthcare resulting in higher patient satisfaction. Telemedicine technology, pushed by the COVID-19 pandemic, has improved asthma management, notably treatment adherence. Smart inhalers, wearable gadgets, and smartphone apps allow doctors to make data-driven decisions and empower patients to manage their diseases. Real-world research shows that TM is effective and patient-friendly. Infrastructure constraints, data security issues, and long-term patient engagement must be addressed. In conclusion, a hybrid strategy combining TM and in-person visits, enabled by AI and secure digital solutions, can provide equal, efficient, and comprehensive asthma management.
DOI: https://doi.org/10.37349/eaa.2025.100974
This article belongs to the special issue The Global Picture of Asthma after Guideline Changes and the COVID Pandemics
Aim:
The increasing prevalence of type 2 diabetes has heightened the demand for low glycemic index food products, leading to the exploration of alternative baking ingredients. This study assesses the effects of bran-enriched flour blends on the sensory, physical, nutritional, and antioxidant properties and glycemic control of high-fiber biscuits.
Methods:
Wheat, corn, sorghum, and sweet potato were obtained from the market. Linear programming (LP) optimized fiber content to create four high-fiber flour blends assessed for functional properties [water absorption capacity (WAC), oil absorption capacity (OAC), foaming capacity (FC), and stability]. Four high-fiber biscuits were developed and evaluated for nutritional composition (ash, crude fibers, water, carbohydrates, proteins, fats, Zn, Fe, Mg, Na, Ca, and P), sensory attributes (color, aroma, texture, and taste), physical properties (thickness, diameter, weight, spread ratio, browning index; L, a, and b), antioxidant properties (DPPH and FRAP activities), glycemic response, and in vitro glucose-binding capacity.
Results:
The formulated flours exhibited water and oil absorption capacities ranging from 1.95% to 2.70%, with the highest oil absorption in formulated flour 3. FC and stability varied significantly, with the control showing the highest values. Swelling power ranged from 1.27 cm3/g to 2.03 cm3/g. High-fiber biscuits had higher fiber (6.06–12.44%), protein (9.48–11.31%), Fe (3.01–4.55 ppm), and Mg (34.37–78.05 ppm) content, and lower carbohydrate (50.88–59.57%) contents compared to the control. They also demonstrated enhanced antioxidant properties with higher phenolic content (201.91–503.18 mg GAE/100 g) and DPPH-scavenging activity (0.07–0.27 µg/mL). Sensory evaluation indicated general acceptance. Biscuits 2 and 3 maintained steady blood glucose levels over 90 min, with biscuit 3 showing the highest in vitro glucose binding capacity (43.4 ± 4.3%).
Conclusions:
Incorporating diverse bran and flour types improves biscuit quality, particularly in blends like F2 (wheat flour, corn bran, and sorghum bran) and F3 (wheat flour, corn bran, sweet potato flour, and sorghum bran), offering beneficial options for diabetics.
Aim:
The increasing prevalence of type 2 diabetes has heightened the demand for low glycemic index food products, leading to the exploration of alternative baking ingredients. This study assesses the effects of bran-enriched flour blends on the sensory, physical, nutritional, and antioxidant properties and glycemic control of high-fiber biscuits.
Methods:
Wheat, corn, sorghum, and sweet potato were obtained from the market. Linear programming (LP) optimized fiber content to create four high-fiber flour blends assessed for functional properties [water absorption capacity (WAC), oil absorption capacity (OAC), foaming capacity (FC), and stability]. Four high-fiber biscuits were developed and evaluated for nutritional composition (ash, crude fibers, water, carbohydrates, proteins, fats, Zn, Fe, Mg, Na, Ca, and P), sensory attributes (color, aroma, texture, and taste), physical properties (thickness, diameter, weight, spread ratio, browning index; L, a, and b), antioxidant properties (DPPH and FRAP activities), glycemic response, and in vitro glucose-binding capacity.
Results:
The formulated flours exhibited water and oil absorption capacities ranging from 1.95% to 2.70%, with the highest oil absorption in formulated flour 3. FC and stability varied significantly, with the control showing the highest values. Swelling power ranged from 1.27 cm3/g to 2.03 cm3/g. High-fiber biscuits had higher fiber (6.06–12.44%), protein (9.48–11.31%), Fe (3.01–4.55 ppm), and Mg (34.37–78.05 ppm) content, and lower carbohydrate (50.88–59.57%) contents compared to the control. They also demonstrated enhanced antioxidant properties with higher phenolic content (201.91–503.18 mg GAE/100 g) and DPPH-scavenging activity (0.07–0.27 µg/mL). Sensory evaluation indicated general acceptance. Biscuits 2 and 3 maintained steady blood glucose levels over 90 min, with biscuit 3 showing the highest in vitro glucose binding capacity (43.4 ± 4.3%).
Conclusions:
Incorporating diverse bran and flour types improves biscuit quality, particularly in blends like F2 (wheat flour, corn bran, and sorghum bran) and F3 (wheat flour, corn bran, sweet potato flour, and sorghum bran), offering beneficial options for diabetics.
DOI: https://doi.org/10.37349/eff.2025.101076
This article belongs to the special issue The food (r)evolution towards food quality/security and human nutrition
Aim:
The study investigates the probiotic potential of exopolysaccharide (EPS)-producing lactic acid bacteria (LAB) isolated from yoghurt samples. It assesses their antimicrobial efficacy against foodborne pathogens, particularly Escherichia coli and Staphylococcus aureus. The objective is to identify LAB strains that can be used as natural preservatives and health-promoting probiotics in functional foods.
Methods:
Yoghurt samples were collected from household local markets in Rawalpindi, Pakistan. LAB was isolated and identified using selective media, Gram staining, and biochemical tests. EPS production was quantified using the phenol-sulfuric acid method. Probiotic properties, including antimicrobial activity against E. coli and S. aureus, were evaluated using the disc diffusion method. Strains producing the highest EPS were biochemically characterised using the API Strep system.
Results:
Of 29 LAB isolates, 12 were identified as significant EPS producers, with Streptococcus thermophilus, Lactococcus lactis, and Limosilactobacillus fermentum demonstrating the highest EPS production (up to 62 µg/mL). These strains exhibited strong antimicrobial activity against E. coli and S. aureus, with inhibition zones ranging from 2 mm to 32.1 mm. The results confirmed the dual functionality of these strains as both texture enhancers and natural preservatives in food products.
Conclusions:
The EPS-producing LAB strains, particularly S. thermophilus, L. lactis, and L. fermentum, showed significant potential as probiotics and natural preservatives. Their antimicrobial activity and ability to enhance food texture suggest their applicability in the food industry to promote health and improve food safety. Further research should explore their stability in different food matrices for commercial use.
Aim:
The study investigates the probiotic potential of exopolysaccharide (EPS)-producing lactic acid bacteria (LAB) isolated from yoghurt samples. It assesses their antimicrobial efficacy against foodborne pathogens, particularly Escherichia coli and Staphylococcus aureus. The objective is to identify LAB strains that can be used as natural preservatives and health-promoting probiotics in functional foods.
Methods:
Yoghurt samples were collected from household local markets in Rawalpindi, Pakistan. LAB was isolated and identified using selective media, Gram staining, and biochemical tests. EPS production was quantified using the phenol-sulfuric acid method. Probiotic properties, including antimicrobial activity against E. coli and S. aureus, were evaluated using the disc diffusion method. Strains producing the highest EPS were biochemically characterised using the API Strep system.
Results:
Of 29 LAB isolates, 12 were identified as significant EPS producers, with Streptococcus thermophilus, Lactococcus lactis, and Limosilactobacillus fermentum demonstrating the highest EPS production (up to 62 µg/mL). These strains exhibited strong antimicrobial activity against E. coli and S. aureus, with inhibition zones ranging from 2 mm to 32.1 mm. The results confirmed the dual functionality of these strains as both texture enhancers and natural preservatives in food products.
Conclusions:
The EPS-producing LAB strains, particularly S. thermophilus, L. lactis, and L. fermentum, showed significant potential as probiotics and natural preservatives. Their antimicrobial activity and ability to enhance food texture suggest their applicability in the food industry to promote health and improve food safety. Further research should explore their stability in different food matrices for commercial use.
DOI: https://doi.org/10.37349/eff.2025.101075
Esketamine, the S-enantiomer of ketamine, has gained prominence as an adjunct in pain management during general anesthesia due to its higher potency and ability to achieve therapeutic effects at lower doses than ketamine. While its benefits for pain relief and mental health are well-established, the specific effects of esketamine on cardiac function during anesthesia remain under investigation. Anesthesia itself induces physiological changes in the cardiovascular system, and esketamine can exacerbate these effects by increasing sympathetic activity, heart rate, blood pressure, and cardiac output. Additionally, it can induce peripheral vasoconstriction, raising systemic vascular resistance. These cardiovascular effects are particularly concerning in patients with pre-existing heart conditions, underscoring the importance of preoperative assessment, continuous monitoring, and potential dose adjustments. This review examined the hemodynamic effects of esketamine, the associated cardiovascular risks, and the clinical implications for patients with cardiac conditions, offering recommendations for its safe use in anesthesia.
Esketamine, the S-enantiomer of ketamine, has gained prominence as an adjunct in pain management during general anesthesia due to its higher potency and ability to achieve therapeutic effects at lower doses than ketamine. While its benefits for pain relief and mental health are well-established, the specific effects of esketamine on cardiac function during anesthesia remain under investigation. Anesthesia itself induces physiological changes in the cardiovascular system, and esketamine can exacerbate these effects by increasing sympathetic activity, heart rate, blood pressure, and cardiac output. Additionally, it can induce peripheral vasoconstriction, raising systemic vascular resistance. These cardiovascular effects are particularly concerning in patients with pre-existing heart conditions, underscoring the importance of preoperative assessment, continuous monitoring, and potential dose adjustments. This review examined the hemodynamic effects of esketamine, the associated cardiovascular risks, and the clinical implications for patients with cardiac conditions, offering recommendations for its safe use in anesthesia.
DOI: https://doi.org/10.37349/emed.2025.1001291
Cervical cancer is the fourth leading cause of cancer-related deaths among women worldwide, causing over 660,000 new cases and 350,000 deaths in 2022, with a disproportionately high burden in low-resource countries where access to treatment is limited. Human papillomavirus (HPV) is a common sexually transmitted infection that accounts for approximately 95% of cervical cancer cases. Persistent HPV infection can progress to cervical dysplasia, categorized into varying severities (CIN1, CIN2, and CIN3), which significantly increases cancer risk. The mechanism of HPV-induced malignancy involves the disruption of cellular apoptosis by integrating viral genetic material into cervical cells, particularly within the transformation zone. The viral proteins E6 and E7 play pivotal roles in cervical carcinogenesis by inhibiting tumor suppressor proteins, promoting uncontrolled cell proliferation, and evading immune responses, ultimately driving progression toward malignancy. Timely detection and intervention are essential for managing HPV-related cervical cancers. Preventative measures such as HPV vaccination have demonstrated substantial efficacy. Six vaccines targeting high-risk (HR) HPV strains are recommended before sexual activity or exposure. Despite these advancements, barriers, such as misinformation, logistical challenges, and limited healthcare infrastructure, persist, particularly in underserved regions. Advances in diagnostic and therapeutic technologies have offered new avenues for addressing these challenges. Next-generation sequencing and CRISPR gene editing are emerging as promising tools for HPV-related cancer treatment that enable precise and targeted interventions. Furthermore, artificial intelligence (AI) and imaging innovations have significantly enhanced diagnostic accuracy and personalized care. Pap smears and HPV DNA testing are indispensable tools for early detection. To tackle HPV-related cervical cancer globally, a multifaceted approach is required. Public health education, vaccination programs, research, and international collaboration are crucial. Public health campaigns should combat misinformation, strengthen vaccination programs, and focus on novel therapies, screening technologies, and next-generation sequencing.
Cervical cancer is the fourth leading cause of cancer-related deaths among women worldwide, causing over 660,000 new cases and 350,000 deaths in 2022, with a disproportionately high burden in low-resource countries where access to treatment is limited. Human papillomavirus (HPV) is a common sexually transmitted infection that accounts for approximately 95% of cervical cancer cases. Persistent HPV infection can progress to cervical dysplasia, categorized into varying severities (CIN1, CIN2, and CIN3), which significantly increases cancer risk. The mechanism of HPV-induced malignancy involves the disruption of cellular apoptosis by integrating viral genetic material into cervical cells, particularly within the transformation zone. The viral proteins E6 and E7 play pivotal roles in cervical carcinogenesis by inhibiting tumor suppressor proteins, promoting uncontrolled cell proliferation, and evading immune responses, ultimately driving progression toward malignancy. Timely detection and intervention are essential for managing HPV-related cervical cancers. Preventative measures such as HPV vaccination have demonstrated substantial efficacy. Six vaccines targeting high-risk (HR) HPV strains are recommended before sexual activity or exposure. Despite these advancements, barriers, such as misinformation, logistical challenges, and limited healthcare infrastructure, persist, particularly in underserved regions. Advances in diagnostic and therapeutic technologies have offered new avenues for addressing these challenges. Next-generation sequencing and CRISPR gene editing are emerging as promising tools for HPV-related cancer treatment that enable precise and targeted interventions. Furthermore, artificial intelligence (AI) and imaging innovations have significantly enhanced diagnostic accuracy and personalized care. Pap smears and HPV DNA testing are indispensable tools for early detection. To tackle HPV-related cervical cancer globally, a multifaceted approach is required. Public health education, vaccination programs, research, and international collaboration are crucial. Public health campaigns should combat misinformation, strengthen vaccination programs, and focus on novel therapies, screening technologies, and next-generation sequencing.
DOI: https://doi.org/10.37349/emed.2025.1001292
In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients.
In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients.
DOI: https://doi.org/10.37349/ei.2025.1003185
This article belongs to the special issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases
Aim:
This randomized clinical trial aimed to investigate the chemo-preventive role of thymoquinone in Nigella sativa extract in managing oral leukoplakia clinically, histologically, and at the molecular level.
Methods:
A total of 48 patients with oral leukoplakia were randomly allocated to three groups; Group A received local muco-adhesive tablets with Nigella sativa extract in 10 mg/kg dose, for three months, Group B same intervention but with Nigella sativa extract in 5 mg/kg dose, and lastly Group C was the placebo group. The outcomes assessed were clinical improvement, histologic improvement (degree of dysplasia), and molecular biomarkers Ki-67 and caspase-3 by immunohistochemistry.
Results:
There was a statistically significant decrease in lesion size in Groups A and B compared to the placebo group. At the molecular level, there was a statistically significant decrease in the expression of Ki-67 in both the Nigella sativa groups compared to the placebo group. While there was a statistically significant increase in caspase-3 in Group A only compared to the other groups.
Conclusions:
Thymoquinone in Nigella sativa extract is a promising chemo-preventive agent that can be used in the management of oral leukoplakia (the trial is registered on clinicaltrials.gov identifier: NCT03208790).
Aim:
This randomized clinical trial aimed to investigate the chemo-preventive role of thymoquinone in Nigella sativa extract in managing oral leukoplakia clinically, histologically, and at the molecular level.
Methods:
A total of 48 patients with oral leukoplakia were randomly allocated to three groups; Group A received local muco-adhesive tablets with Nigella sativa extract in 10 mg/kg dose, for three months, Group B same intervention but with Nigella sativa extract in 5 mg/kg dose, and lastly Group C was the placebo group. The outcomes assessed were clinical improvement, histologic improvement (degree of dysplasia), and molecular biomarkers Ki-67 and caspase-3 by immunohistochemistry.
Results:
There was a statistically significant decrease in lesion size in Groups A and B compared to the placebo group. At the molecular level, there was a statistically significant decrease in the expression of Ki-67 in both the Nigella sativa groups compared to the placebo group. While there was a statistically significant increase in caspase-3 in Group A only compared to the other groups.
Conclusions:
Thymoquinone in Nigella sativa extract is a promising chemo-preventive agent that can be used in the management of oral leukoplakia (the trial is registered on clinicaltrials.gov identifier: NCT03208790).
DOI: https://doi.org/10.37349/emed.2025.1001290
Biosimilars are biologic products that provide equal mechanisms and efficacy to that of their original biologic references. This paper aims to provide a comprehensive overview of the numerous ways biosimilars are improving care for individuals living with rheumatoid arthritis (RA), from the effective application of biosimilars in treatment-naive RA patients, switching from an original biologic to a biosimilar, to the ability to tailor biologic therapy in respect to mechanisms provided by different biologic classes. Biosimilars provide a significant reduction in cost and provide patients with treatment options that do not exhibit adverse drug reactions (ADRs) as exhibited with methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Understanding mechanisms to discern patient response to biologic therapies will gain increasing importance as biosimilars with different targeted mechanisms enter the market. Patients who do not respond to one class of biologic medicine now have alternative biosimilars available to support their care. Study results support that patients initiated on biosimilars stay on biosimilars, so it is prudent to remain aware of the biosimilars available and candidates in development.
Biosimilars are biologic products that provide equal mechanisms and efficacy to that of their original biologic references. This paper aims to provide a comprehensive overview of the numerous ways biosimilars are improving care for individuals living with rheumatoid arthritis (RA), from the effective application of biosimilars in treatment-naive RA patients, switching from an original biologic to a biosimilar, to the ability to tailor biologic therapy in respect to mechanisms provided by different biologic classes. Biosimilars provide a significant reduction in cost and provide patients with treatment options that do not exhibit adverse drug reactions (ADRs) as exhibited with methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Understanding mechanisms to discern patient response to biologic therapies will gain increasing importance as biosimilars with different targeted mechanisms enter the market. Patients who do not respond to one class of biologic medicine now have alternative biosimilars available to support their care. Study results support that patients initiated on biosimilars stay on biosimilars, so it is prudent to remain aware of the biosimilars available and candidates in development.
DOI: https://doi.org/10.37349/emd.2025.100787
This article belongs to the special issue Biosimilars: State of the Art in the Treatment of Rheumatic Diseases
Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. Persistent infection with high-risk human papillomavirus (HPV) is the primary etiological factor, leading to immune evasion mechanisms that promote tumor development and progression. Immunotherapy has emerged as a transformative approach in the management of cervical cancer, aiming to restore and enhance the body’s immune response against tumor cells. Checkpoint inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1) have shown promising results in patients with advanced or recurrent cervical cancer. Pembrolizumab, a PD-1 inhibitor, has been approved for PD-L1-positive cervical cancer, demonstrating durable responses. However, low response rates necessitate exploration of combination strategies. Trials are underway combining checkpoint inhibitors with chemotherapy, radiation, or other immunotherapeutic agents to enhance efficacy. Therapeutic vaccines targeting HPV antigens, such as E6 and E7 oncoproteins, are also a focus of active research. These vaccines aim to elicit robust cytotoxic T-cell responses, offering a potential strategy for early intervention and disease control. Adoptive T-cell therapies, including engineered T-cell receptor (TCR) and chimeric antigen receptor (CAR)-T cells, represent cutting-edge advancements, though challenges with tumor heterogeneity and off-target effects persist. However, challenges such as limited response rates and immune evasion mechanisms remain. The tumor microenvironment (TME) in cervical cancer, characterized by immunosuppressive cells and cytokines, poses a significant barrier to effective immunotherapy. Emerging approaches targeting the TME, such as cytokine modulation, hold promise in overcoming resistance mechanisms. Key gaps include a lack of biomarkers for patient selection, insufficient understanding of TME dynamics, and suboptimal strategies for overcoming antigen heterogeneity and immune resistance. This review addresses these issues by providing a comprehensive analysis of the current landscape of cervical cancer immunotherapy, identifying critical barriers, and highlighting emerging approaches, such as combination therapies, novel immune targets, and strategies to modulate the TME, to guide future research and clinical practice.
Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. Persistent infection with high-risk human papillomavirus (HPV) is the primary etiological factor, leading to immune evasion mechanisms that promote tumor development and progression. Immunotherapy has emerged as a transformative approach in the management of cervical cancer, aiming to restore and enhance the body’s immune response against tumor cells. Checkpoint inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1) have shown promising results in patients with advanced or recurrent cervical cancer. Pembrolizumab, a PD-1 inhibitor, has been approved for PD-L1-positive cervical cancer, demonstrating durable responses. However, low response rates necessitate exploration of combination strategies. Trials are underway combining checkpoint inhibitors with chemotherapy, radiation, or other immunotherapeutic agents to enhance efficacy. Therapeutic vaccines targeting HPV antigens, such as E6 and E7 oncoproteins, are also a focus of active research. These vaccines aim to elicit robust cytotoxic T-cell responses, offering a potential strategy for early intervention and disease control. Adoptive T-cell therapies, including engineered T-cell receptor (TCR) and chimeric antigen receptor (CAR)-T cells, represent cutting-edge advancements, though challenges with tumor heterogeneity and off-target effects persist. However, challenges such as limited response rates and immune evasion mechanisms remain. The tumor microenvironment (TME) in cervical cancer, characterized by immunosuppressive cells and cytokines, poses a significant barrier to effective immunotherapy. Emerging approaches targeting the TME, such as cytokine modulation, hold promise in overcoming resistance mechanisms. Key gaps include a lack of biomarkers for patient selection, insufficient understanding of TME dynamics, and suboptimal strategies for overcoming antigen heterogeneity and immune resistance. This review addresses these issues by providing a comprehensive analysis of the current landscape of cervical cancer immunotherapy, identifying critical barriers, and highlighting emerging approaches, such as combination therapies, novel immune targets, and strategies to modulate the TME, to guide future research and clinical practice.
DOI: https://doi.org/10.37349/etat.2025.1002296
This article belongs to the special issue Comprehensive Immunotherapy of Solid Tumors
Aim:
This study evaluates the efficacy of amino-functionalized mesoporous silica nanoparticles (MSNs) in the controlled release of dexamethasone phosphate (DexaP), aiming to enhance therapeutic outcomes and minimize systemic toxicity.
Methods:
In this study, amino-functionalized MSNs were synthesized using a modified Stöber process and characterized their chemical and physical properties through various analytical techniques. The study focused on the adsorption and release kinetics of DexaP, employing multiple kinetic models to explore the interaction dynamics.
Results:
The amino-functionalized MSNs demonstrated effective DexaP loading and controlled release profiles. The kinetic analysis revealed a predominance of chemisorptive interactions, supporting sustained drug release. Enhanced biocompatibility was confirmed through cytotoxicity assays.
Conclusions:
Amino-functionalized MSNs offer a promising platform for the targeted and controlled delivery of anti-inflammatory drugs, with significant potential to improve patient adherence and reduce adverse effects. The findings advocate for further development of MSNs as a versatile tool in advanced drug delivery systems.
Aim:
This study evaluates the efficacy of amino-functionalized mesoporous silica nanoparticles (MSNs) in the controlled release of dexamethasone phosphate (DexaP), aiming to enhance therapeutic outcomes and minimize systemic toxicity.
Methods:
In this study, amino-functionalized MSNs were synthesized using a modified Stöber process and characterized their chemical and physical properties through various analytical techniques. The study focused on the adsorption and release kinetics of DexaP, employing multiple kinetic models to explore the interaction dynamics.
Results:
The amino-functionalized MSNs demonstrated effective DexaP loading and controlled release profiles. The kinetic analysis revealed a predominance of chemisorptive interactions, supporting sustained drug release. Enhanced biocompatibility was confirmed through cytotoxicity assays.
Conclusions:
Amino-functionalized MSNs offer a promising platform for the targeted and controlled delivery of anti-inflammatory drugs, with significant potential to improve patient adherence and reduce adverse effects. The findings advocate for further development of MSNs as a versatile tool in advanced drug delivery systems.
DOI: https://doi.org/10.37349/eds.2025.100895
Aim:
Cough is an important symptom of the combined course of bronchial asthma (BA) and allergic rhinitis (AR) and/or allergic rhinosinusitis (ARS), but the contribution of the pathology of the upper and lower airway to the formation of cough in these patients cannot be considered established. The aim of the study was to evaluate the relationship of cough intensity with indicators of external respiration and nasal respiratory function in children and adolescents with a combined course of BA and AR and/or ARS.
Methods:
It was a single-center observational transverse pilot study. The absence and/or presence of cough and its intensity were scored in 122 patients (14.0 [11.0; 16.0] years) using the Sinonasal Outcome Test–22 (SNOT-22). Groups were identified: 1 (n = 29)—no cough (0 points), 2 (n = 72)—mild cough (1–2 points), 3 (n = 21)—moderate cough (3–4 points). Peak nasal inspiratory flow (PNIF) and spirometric parameters were measured.
Results:
Assessment of cough by patients using the SNOT-22 test had negative correlations with spirometric indicators: z FEV1 and z FEV1/FVC (r = –0.23, P = 0.012 and r = –0.21, P = 0.023, respectively). A positive relationship was noted with changes in FEV1 in tests with bronchodilators (r = 0.43, P = 0.002) and with the severity of postnasal drip (r = 0.45, P < 0.001 and r = 0.43, P < 0.001, respectively).
Conclusions:
Established correlations of cough intensity with spirometry indicators and with symptoms of postnasal drip in patients with combined BA and AR/ARS indicate the participation of both the upper and lower respiratory tract in the formation of cough.
Aim:
Cough is an important symptom of the combined course of bronchial asthma (BA) and allergic rhinitis (AR) and/or allergic rhinosinusitis (ARS), but the contribution of the pathology of the upper and lower airway to the formation of cough in these patients cannot be considered established. The aim of the study was to evaluate the relationship of cough intensity with indicators of external respiration and nasal respiratory function in children and adolescents with a combined course of BA and AR and/or ARS.
Methods:
It was a single-center observational transverse pilot study. The absence and/or presence of cough and its intensity were scored in 122 patients (14.0 [11.0; 16.0] years) using the Sinonasal Outcome Test–22 (SNOT-22). Groups were identified: 1 (n = 29)—no cough (0 points), 2 (n = 72)—mild cough (1–2 points), 3 (n = 21)—moderate cough (3–4 points). Peak nasal inspiratory flow (PNIF) and spirometric parameters were measured.
Results:
Assessment of cough by patients using the SNOT-22 test had negative correlations with spirometric indicators: z FEV1 and z FEV1/FVC (r = –0.23, P = 0.012 and r = –0.21, P = 0.023, respectively). A positive relationship was noted with changes in FEV1 in tests with bronchodilators (r = 0.43, P = 0.002) and with the severity of postnasal drip (r = 0.45, P < 0.001 and r = 0.43, P < 0.001, respectively).
Conclusions:
Established correlations of cough intensity with spirometry indicators and with symptoms of postnasal drip in patients with combined BA and AR/ARS indicate the participation of both the upper and lower respiratory tract in the formation of cough.
DOI: https://doi.org/10.37349/emed.2025.1001288
This review explored the physiological mechanisms underlying arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus) and AVP resistance (AVP-R, formerly nephrogenic diabetes insipidus), with a focus on water balance regulation. Vital components include the hypothalamic-pituitary-AVP axis, renal AVP responsiveness, and neural mechanisms of thirst regulation. Recent insights on thirst generation within circumventricular brain nuclei (subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis) are discussed, along with the diagnostic utility of copeptin in polyuric states. This review highlighted the critical role of hypothalamic-pituitary integrity and renal AVP responsiveness in maintaining water-electrolyte homeostasis. Understanding these mechanisms provided the foundation for optimizing therapeutic strategies and advancing research on AVP-related disorders.
This review explored the physiological mechanisms underlying arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus) and AVP resistance (AVP-R, formerly nephrogenic diabetes insipidus), with a focus on water balance regulation. Vital components include the hypothalamic-pituitary-AVP axis, renal AVP responsiveness, and neural mechanisms of thirst regulation. Recent insights on thirst generation within circumventricular brain nuclei (subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis) are discussed, along with the diagnostic utility of copeptin in polyuric states. This review highlighted the critical role of hypothalamic-pituitary integrity and renal AVP responsiveness in maintaining water-electrolyte homeostasis. Understanding these mechanisms provided the foundation for optimizing therapeutic strategies and advancing research on AVP-related disorders.
DOI: https://doi.org/10.37349/emed.2025.1001289
Aim:
The objective of this study was to develop a minimal physiologically based pharmacokinetic (mPBPK) model to predict area under the curve (AUC) and maximum plasma concentration (Cmax) of drugs in subjects with varying degrees of hepatic impairment and compare this mPBPK model with the whole body PBPK model.
Methods:
Hepatic impairment classification system, which is based on Child-Pugh score was used. In this mPBPK model, 4 physiological parameters [portal and renal blood flow, glomerular filtration rate (GFR), and liver size] and 2 biochemical parameters (albumin and bilirubin) were used. Total number of drugs analyzed in this study was 52, and the predicted Cmax and AUC values were compared with dedicated clinical trials. Out of 52 drugs, the predictive performance of mPBPK was compared with the whole body PBPK model for 27 drugs, and the remaining 25 drugs were used to further test the robustness of the mPBPK model.
Results:
The results of the study indicated that the predictive performance of the mPBPK model was comparable with the whole body PBPK model, both in terms of Cmax and AUC. For 52 drugs, there were 120 data points for AUC (37, 47, and 36 for mild, moderate, and severe hepatic impairment, respectively), and from mPBPK model, 92%, 94%, and 89% data points were within 0.5–2-fold prediction error, respectively.
Conclusions:
Overall, the results of the study indicated that the proposed mPBPK model, in its predictive performance, is as robust and accurate as whole body PBPK model.
Aim:
The objective of this study was to develop a minimal physiologically based pharmacokinetic (mPBPK) model to predict area under the curve (AUC) and maximum plasma concentration (Cmax) of drugs in subjects with varying degrees of hepatic impairment and compare this mPBPK model with the whole body PBPK model.
Methods:
Hepatic impairment classification system, which is based on Child-Pugh score was used. In this mPBPK model, 4 physiological parameters [portal and renal blood flow, glomerular filtration rate (GFR), and liver size] and 2 biochemical parameters (albumin and bilirubin) were used. Total number of drugs analyzed in this study was 52, and the predicted Cmax and AUC values were compared with dedicated clinical trials. Out of 52 drugs, the predictive performance of mPBPK was compared with the whole body PBPK model for 27 drugs, and the remaining 25 drugs were used to further test the robustness of the mPBPK model.
Results:
The results of the study indicated that the predictive performance of the mPBPK model was comparable with the whole body PBPK model, both in terms of Cmax and AUC. For 52 drugs, there were 120 data points for AUC (37, 47, and 36 for mild, moderate, and severe hepatic impairment, respectively), and from mPBPK model, 92%, 94%, and 89% data points were within 0.5–2-fold prediction error, respectively.
Conclusions:
Overall, the results of the study indicated that the proposed mPBPK model, in its predictive performance, is as robust and accurate as whole body PBPK model.
DOI: https://doi.org/10.37349/eds.2025.100894
Aim:
To assess the predictive and prognostic role of HLA class I expression in patients with melanoma (Mel), and soft tissue sarcomas (STS) treated with autologous dendritic cell vaccine (DCV) (CaTeVac).
Methods:
From 2009 to 2023, 277 patients with Mel (143), and STS (134), received DCV at the N.N. Petrov National Medical Research Center of Oncology in adjuvant (78.3% and 14.9%) and therapeutic (21.7% and 85.1%) setting. HLA-typing was performed using a polymerase chain reaction with sequence-specific primers (PCR-SSP). Progression-free survival (PFS) and overall survival (OS) grouped by the presence of HLA alleles or HLA association rules were assessed using the Kaplan-Meier method (medians of survival in the month are presented).
Results:
Higher OS (41.1 vs. 22.1, P = 0.026) and PFS (6.0 vs. 3.9, P = 0.045) were found in HLA-A heterozygous STS patients, while HLA-B homozygous patients showed better OS (36.4 vs. 87.2, P = 0.023). HLA-A heterozygous Mel patients showed lower PFS (8.3 vs. not reached, P = 0.013). Association rules analysis on HLA expression revealed 20 rules with high confidence, seven of which were associated with the survival. HLA-B*07 and HLA-C*07 (21.2 vs. 52.2), HLA-B*40 and HLA-C*03 (17.6 vs. 45.4), HLA-A*02 and HLA-B*07 and HLA-C*07 (16.8 vs. 47.0), HLA-A*02 and HLA-С*07 (17.6 vs. 41.1), HLA-B*40 and HLA-A*02 and HLA-C*03 (8.3 vs. 50.2) decreased OS in STS (P < 0.05). HLA-A*02 and HLA-B*07 and HLA-C*07 (3.2 vs. 6.0), HLA-B*40 and HLA-A*02 and HLA-C*03 (3.2 vs. 5.9) decreased PFS in STS patients (P < 0.05). HLA-B*35 and HLA-C*04 increased median OS in STS from 33.4 to 153.3 months.
Conclusions:
HLA class I phenotype has a different impact on the survival in Mel and STS patients. The association rules based on HLA coexpression may have prognostic and predictive value. Further investigations of these parameters are warranted (The Trial Registration Number: NCT05539677).
Aim:
To assess the predictive and prognostic role of HLA class I expression in patients with melanoma (Mel), and soft tissue sarcomas (STS) treated with autologous dendritic cell vaccine (DCV) (CaTeVac).
Methods:
From 2009 to 2023, 277 patients with Mel (143), and STS (134), received DCV at the N.N. Petrov National Medical Research Center of Oncology in adjuvant (78.3% and 14.9%) and therapeutic (21.7% and 85.1%) setting. HLA-typing was performed using a polymerase chain reaction with sequence-specific primers (PCR-SSP). Progression-free survival (PFS) and overall survival (OS) grouped by the presence of HLA alleles or HLA association rules were assessed using the Kaplan-Meier method (medians of survival in the month are presented).
Results:
Higher OS (41.1 vs. 22.1, P = 0.026) and PFS (6.0 vs. 3.9, P = 0.045) were found in HLA-A heterozygous STS patients, while HLA-B homozygous patients showed better OS (36.4 vs. 87.2, P = 0.023). HLA-A heterozygous Mel patients showed lower PFS (8.3 vs. not reached, P = 0.013). Association rules analysis on HLA expression revealed 20 rules with high confidence, seven of which were associated with the survival. HLA-B*07 and HLA-C*07 (21.2 vs. 52.2), HLA-B*40 and HLA-C*03 (17.6 vs. 45.4), HLA-A*02 and HLA-B*07 and HLA-C*07 (16.8 vs. 47.0), HLA-A*02 and HLA-С*07 (17.6 vs. 41.1), HLA-B*40 and HLA-A*02 and HLA-C*03 (8.3 vs. 50.2) decreased OS in STS (P < 0.05). HLA-A*02 and HLA-B*07 and HLA-C*07 (3.2 vs. 6.0), HLA-B*40 and HLA-A*02 and HLA-C*03 (3.2 vs. 5.9) decreased PFS in STS patients (P < 0.05). HLA-B*35 and HLA-C*04 increased median OS in STS from 33.4 to 153.3 months.
Conclusions:
HLA class I phenotype has a different impact on the survival in Mel and STS patients. The association rules based on HLA coexpression may have prognostic and predictive value. Further investigations of these parameters are warranted (The Trial Registration Number: NCT05539677).
DOI: https://doi.org/10.37349/emed.2025.1001287
Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation, B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination of B. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use.
Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation, B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination of B. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use.
DOI: https://doi.org/10.37349/eds.2025.100893
A potential solution for prosthetic heart valves is tissue-engineered heart valves. Tissue-engineered heart valves (TEHVs) are designed to replicate the complex properties found in natural tissues, such as stiffness, anisotropy, and composition and organization of cells and extracellular matrix (ECM). Electrospinning is regarded as a highly versatile and innovative approach for fabricating numerous fibrous designs. In this review, we discuss recent developments in electrospun heart valve scaffolds, including scaffold materials, cell types, and electrospinning setups used to prepare aligned nanofibers. Despite the fact that natural biomaterials provided excellent biocompatibility, nanofibers from synthetic materials provided the required mechanical compatibility. Accordingly, most studies highlighted the benefits of designing composite heart valves using biological and synthetic polymers. Various strategies, such as the application of motorized mandrel and micropatterned collector in electrospinning were effective in controlling nanofiber alignment. Studies also showed that aligned nanofiber’s mechanical strength and anisotropic structure promote cell proliferation, and differentiation, and promote attachment. Numerous studies have reported that multiple cell sources are suitable for producing heart valves. Successful results were obtained with human umbilical vein endothelial cells (HUVECs), since they provide a convenient cell source for cellularization of valve leaflets. A higher conductivity of scaffolds was achieved by using biomaterials that conduct electricity, such as polyaniline, polypyrrole, and carbon nanotubes, which resulted in better differentiation of precursor cells to cardiomyocytes and higher cell beating rates. In light of these attributes, nanofibrous scaffolds produced through electrospinning are expected to offer numerous advantages for tissue engineering and medical applications in the near future. However, multiple challenges were identified as cell infiltration and 2D nature of nanofiber mats necessitate further engineering approaches in electrospinning procedure leaflet production.
A potential solution for prosthetic heart valves is tissue-engineered heart valves. Tissue-engineered heart valves (TEHVs) are designed to replicate the complex properties found in natural tissues, such as stiffness, anisotropy, and composition and organization of cells and extracellular matrix (ECM). Electrospinning is regarded as a highly versatile and innovative approach for fabricating numerous fibrous designs. In this review, we discuss recent developments in electrospun heart valve scaffolds, including scaffold materials, cell types, and electrospinning setups used to prepare aligned nanofibers. Despite the fact that natural biomaterials provided excellent biocompatibility, nanofibers from synthetic materials provided the required mechanical compatibility. Accordingly, most studies highlighted the benefits of designing composite heart valves using biological and synthetic polymers. Various strategies, such as the application of motorized mandrel and micropatterned collector in electrospinning were effective in controlling nanofiber alignment. Studies also showed that aligned nanofiber’s mechanical strength and anisotropic structure promote cell proliferation, and differentiation, and promote attachment. Numerous studies have reported that multiple cell sources are suitable for producing heart valves. Successful results were obtained with human umbilical vein endothelial cells (HUVECs), since they provide a convenient cell source for cellularization of valve leaflets. A higher conductivity of scaffolds was achieved by using biomaterials that conduct electricity, such as polyaniline, polypyrrole, and carbon nanotubes, which resulted in better differentiation of precursor cells to cardiomyocytes and higher cell beating rates. In light of these attributes, nanofibrous scaffolds produced through electrospinning are expected to offer numerous advantages for tissue engineering and medical applications in the near future. However, multiple challenges were identified as cell infiltration and 2D nature of nanofiber mats necessitate further engineering approaches in electrospinning procedure leaflet production.
DOI: https://doi.org/10.37349/ebmx.2025.101331
This article belongs to the special issue Trends in Biomaterials Research for Cardiovascular Applications
The epidemic of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly growing worldwide. Thus, there is an urgent need for novel, non-invasive, and reliable biomarkers to replace liver biopsy for the diagnosis and prognosis of MASLD. Circulating peripheral blood mononuclear cells (PBMCs) are highly responsive to various stimuli and physiological changes. Beyond their immunomodulatory role, PBMC may act as metabolic sensors in several cardiometabolic disorders, including MASLD, with their metabolic programs shifting accordingly. Recent evidence suggests a link between impaired mitochondrial bioenergetics in PBMC and MASLD. Additionally, impaired mitochondrial respiration is intricately linked to the intracellular depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) in various cell types. Accumulating preclinical and clinical data show that NAD+-increasing strategies may protect against MASLD by restoring intracellular NAD+ pools and improving mitochondrial performance. This review will focus on [i] the relevance of mitochondrial dysfunction, including impaired bioenergetics, in PBMC as a marker for the diagnosis and prognosis of MASLD, and [ii] the potential benefits of NAD+ precursors in MAFLD and their relationship with improved mitochondrial respiration in blood immune cells.
The epidemic of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly growing worldwide. Thus, there is an urgent need for novel, non-invasive, and reliable biomarkers to replace liver biopsy for the diagnosis and prognosis of MASLD. Circulating peripheral blood mononuclear cells (PBMCs) are highly responsive to various stimuli and physiological changes. Beyond their immunomodulatory role, PBMC may act as metabolic sensors in several cardiometabolic disorders, including MASLD, with their metabolic programs shifting accordingly. Recent evidence suggests a link between impaired mitochondrial bioenergetics in PBMC and MASLD. Additionally, impaired mitochondrial respiration is intricately linked to the intracellular depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) in various cell types. Accumulating preclinical and clinical data show that NAD+-increasing strategies may protect against MASLD by restoring intracellular NAD+ pools and improving mitochondrial performance. This review will focus on [i] the relevance of mitochondrial dysfunction, including impaired bioenergetics, in PBMC as a marker for the diagnosis and prognosis of MASLD, and [ii] the potential benefits of NAD+ precursors in MAFLD and their relationship with improved mitochondrial respiration in blood immune cells.
DOI: https://doi.org/10.37349/edd.2025.100566
This article belongs to the special issue Mitochondria and Lipid Signalling in Liver Diseases
Protein phosphorylation is a fundamental regulatory mechanism governing a broad spectrum of cellular processes. In the nervous system, it is critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation of protein kinase activity is closely linked to the pathogenesis of various neurological and psychiatric disorders, positioning several kinases as promising therapeutic targets. Although protein kinase inhibitors (PKIs), a major class of compounds that modulate kinase activity, have shown considerable therapeutic success in oncology, their application in neurological diseases remains in the early stages of exploration. Of the 82 PKIs approved by the Food and Drug Administration (FDA), 37 are now in various preclinical and clinical trials for neurological conditions, primarily targeting signaling pathways mediated by key protein kinases implicated in these diseases. This review examines the roles of critical protein kinases and the therapeutic effects of their inhibitors in neurodegenerative, psychiatric, and selected neurological disorders, such as autism spectrum disorders (ASD) and epilepsy. We focus on Abelson kinase I (ABL1), calmodulin-dependent kinase II (CaMKII), casein kinase 1δ (CK1δ), c-Jun N-terminal kinase (JNK), cyclin-dependent kinase 5 (CDK5), dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), leucine-rich repeat kinase 2 (LRRK2), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase, and protein kinase C (PKC) in neurodegenerative diseases. Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, protein kinase A (PKA), and PKC in psychiatric disorders, focusing on schizophrenia and mood disorders, and analyze GSK3β, ERK1/2, and mTOR in ASD and epilepsy. This review underscores the therapeutic potential of PKIs in neurological disorders while highlighting ongoing challenges and the need for further research to refine kinase-targeted therapies.
Protein phosphorylation is a fundamental regulatory mechanism governing a broad spectrum of cellular processes. In the nervous system, it is critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation of protein kinase activity is closely linked to the pathogenesis of various neurological and psychiatric disorders, positioning several kinases as promising therapeutic targets. Although protein kinase inhibitors (PKIs), a major class of compounds that modulate kinase activity, have shown considerable therapeutic success in oncology, their application in neurological diseases remains in the early stages of exploration. Of the 82 PKIs approved by the Food and Drug Administration (FDA), 37 are now in various preclinical and clinical trials for neurological conditions, primarily targeting signaling pathways mediated by key protein kinases implicated in these diseases. This review examines the roles of critical protein kinases and the therapeutic effects of their inhibitors in neurodegenerative, psychiatric, and selected neurological disorders, such as autism spectrum disorders (ASD) and epilepsy. We focus on Abelson kinase I (ABL1), calmodulin-dependent kinase II (CaMKII), casein kinase 1δ (CK1δ), c-Jun N-terminal kinase (JNK), cyclin-dependent kinase 5 (CDK5), dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), leucine-rich repeat kinase 2 (LRRK2), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase, and protein kinase C (PKC) in neurodegenerative diseases. Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, protein kinase A (PKA), and PKC in psychiatric disorders, focusing on schizophrenia and mood disorders, and analyze GSK3β, ERK1/2, and mTOR in ASD and epilepsy. This review underscores the therapeutic potential of PKIs in neurological disorders while highlighting ongoing challenges and the need for further research to refine kinase-targeted therapies.
DOI: https://doi.org/10.37349/eds.2025.100892
This article belongs to the special issue Leveraging the FDA-Approved Kinase Inhibitors to Treat Neurological Disorders
Aim:
In this study, the physicochemical properties of stearyl glycyrrhetinate/β-cyclodextrin (SG/βCD) and SG/γCD complexes were characterized, and the complexes were prepared using the co-milling method. The molecular interactions within the SG/CD complexes were also investigated using nuclear magnetic resonance (NMR) measurements to determine the mode of interaction.
Methods:
Here, we evaluated the physicochemical properties of SG complexes with CDs prepared by ground mixtures (GM SG/βCD or γCD = 1/1, 1/2).
Results:
Powder X-ray diffraction (PXRD) showed that the characteristic SG and CD peaks disappeared after co-grinding with GM (SG/CD = molar ratio of 1/2), indicating a halo pattern. Differential scanning calorimetry (DSC) measurements showed that after co-grinding, the endothermic peak due to SG melting, as well as the dehydration peak and the endothermic peak due to SG melting, disappeared. Near-infrared (NIR) spectroscopy results showed that the peaks of SG-derived –CH moieties and CD-derived –OH and –CH moieties broadened in GM, suggesting their involvement in complex formation through SG/CDs intermolecular interactions. In GM (SG/CDs), NMR measurements showed broadened H-A and H-F peaks of the steroid skeleton derived from SG. In GM (SG/βCD = 1/2), the doublet peak, especially OH-3 at the wide edge of CD, shifted to a singlet peak. In GM (SG/γCD = 1/2), the H-3 peak, which is the wide edge of γCD, and the H-6 peak, which is the narrow edge, shifted to broad peaks, suggesting that γCD is deeply encapsulated in the steroidal structure.
Conclusions:
These findings suggest that complex formation occurred in SG/CDs and that inclusion behavior is different between GM (SG/βCD = 1/2) and GM (SG/γCD = 1/2).
Aim:
In this study, the physicochemical properties of stearyl glycyrrhetinate/β-cyclodextrin (SG/βCD) and SG/γCD complexes were characterized, and the complexes were prepared using the co-milling method. The molecular interactions within the SG/CD complexes were also investigated using nuclear magnetic resonance (NMR) measurements to determine the mode of interaction.
Methods:
Here, we evaluated the physicochemical properties of SG complexes with CDs prepared by ground mixtures (GM SG/βCD or γCD = 1/1, 1/2).
Results:
Powder X-ray diffraction (PXRD) showed that the characteristic SG and CD peaks disappeared after co-grinding with GM (SG/CD = molar ratio of 1/2), indicating a halo pattern. Differential scanning calorimetry (DSC) measurements showed that after co-grinding, the endothermic peak due to SG melting, as well as the dehydration peak and the endothermic peak due to SG melting, disappeared. Near-infrared (NIR) spectroscopy results showed that the peaks of SG-derived –CH moieties and CD-derived –OH and –CH moieties broadened in GM, suggesting their involvement in complex formation through SG/CDs intermolecular interactions. In GM (SG/CDs), NMR measurements showed broadened H-A and H-F peaks of the steroid skeleton derived from SG. In GM (SG/βCD = 1/2), the doublet peak, especially OH-3 at the wide edge of CD, shifted to a singlet peak. In GM (SG/γCD = 1/2), the H-3 peak, which is the wide edge of γCD, and the H-6 peak, which is the narrow edge, shifted to broad peaks, suggesting that γCD is deeply encapsulated in the steroidal structure.
Conclusions:
These findings suggest that complex formation occurred in SG/CDs and that inclusion behavior is different between GM (SG/βCD = 1/2) and GM (SG/γCD = 1/2).
DOI: https://doi.org/10.37349/ebmx.2025.101330
This article belongs to the special issue Nature-Based Biomaterials for Biomedical Applications
