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Search Results (398)

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11 pages, 620 KB  
Article
Impact of Colchicine Therapy on Ventriculoarterial Coupling in Familial Mediterranean Fever: A Cross-Sectional Study
by Hakan Duman, Hüseyin Durak, Osman Cüre, Mustafa Çetin, Ali Gökhan Özyıldız, Elif Ergül, Müjgan Ayşenur Şahin, Ahmet Özsipahi, Ahmet Yasin Tuncer, Barış Dindar and Nadir Emlek
J. Clin. Med. 2025, 14(19), 6902; https://doi.org/10.3390/jcm14196902 - 29 Sep 2025
Viewed by 213
Abstract
Background: Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disorder that is characterized by increased arterial stiffness and subtle cardiovascular dysfunction. Colchicine remains the mainstay of treatment and may provide vascular benefits that extend beyond its anti-inflammatory effects. However, the association between colchicine [...] Read more.
Background: Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disorder that is characterized by increased arterial stiffness and subtle cardiovascular dysfunction. Colchicine remains the mainstay of treatment and may provide vascular benefits that extend beyond its anti-inflammatory effects. However, the association between colchicine therapy and ventriculoarterial coupling (VAC), a hemodynamic marker of cardiovascular efficiency, has not been previously studied. Methods: In this cross-sectional study, 97 patients with FMF receiving colchicine therapy for at least one year and 81 colchicine-naive individuals without FMF were consecutively enrolled from a tertiary rheumatology outpatient clinic. The VAC was evaluated using the Chen method, calculated as the ratio of arterial elastance (Ea) to end-systolic elastance (Es), based on echocardiographic measurements and noninvasive brachial blood pressure. Correlation analyses and stepwise multivariate linear regression analyses were performed to identify independent predictors of VAC. Results: Patients with FMF demonstrated significantly lower VAC values compared to controls (1.23 ± 0.34 vs. 1.40 ± 0.57; p = 0.001). The colchicine dose was inversely correlated with VAC (r = −0.243; p = 0.001) and remained an independent predictor in multivariate analysis (β = −0.186, p = 0.018). Beta-blocker use was positively associated with VAC (β = 0.194, p = 0.014), whereas female sex showed a borderline inverse association. Conclusions: Colchicine use in patients with FMF was associated with more favorable VAC in a dose-dependent manner. These findings suggest that colchicine may exert cardiovascular effects beyond the control of inflammation. VAC may be a useful noninvasive marker for assessing vascular–ventricular interactions in FMF. Full article
(This article belongs to the Special Issue Cardiovascular Risks in Autoimmune and Inflammatory Diseases)
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19 pages, 7603 KB  
Article
Comparative Efficiencies of TiO2 Photocatalysts on β-Blocker Metoprolol Degradation by Solar Heterogeneous Photocatalysis
by Irma C. Torrecillas-Rodríguez, Francisco Rodríguez-González, Daniel Tapia-Maruri, Héctor J. Dorantes-Rosales, José L. Molina-González, Cynthia M. Núñez-Núñez and José B. Proal-Nájera
Nanomaterials 2025, 15(18), 1445; https://doi.org/10.3390/nano15181445 - 19 Sep 2025
Viewed by 373
Abstract
The degradation of metoprolol (MET) has become a topic of interest due to its persistence in the environment. TiO2 is a catalyst commonly used for the degradation of emergent pollutants through photocatalysis due to its physicochemical properties, and it has been pointed [...] Read more.
The degradation of metoprolol (MET) has become a topic of interest due to its persistence in the environment. TiO2 is a catalyst commonly used for the degradation of emergent pollutants through photocatalysis due to its physicochemical properties, and it has been pointed out that its crystallite structure and size affect the photocatalytic efficiency. In this study, three brands of TiO2 (Evonik P25, Fermont and Sigma Aldrich) were characterized to evaluate their crystallographic and morphological properties. Then, their photocatalytic capacity was tested in solar heterogeneous photocatalysis experiments when degrading MET under various experimental conditions. The TiO2 catalysts tested yielded different results when degrading MET in photocatalytic experiments, indicating that presence of a rutile phase in the catalyst and the crystal size are important factors for the success of this semiconductor. Results from solar heterogeneous photocatalysis for MET degradation indicate efficiencies as P25 > Sigma-Aldrich > Fermont, but demonstrate that, even lower-priced TiO2 catalysts yield good results for contaminant degradation (90% MET degradation for P25 against 63% when using Sigma Aldrich TiO2). This study highlights the potential of solar photocatalysis with lower-priced TiO2 catalysts as a viable and sustainable solution for the decontamination of pharmaceutical wastewater in large scale photocatalytic applications. Full article
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14 pages, 985 KB  
Article
Targeted Heart Rate Control with Landiolol in Hemodynamically Unstable, Non-Surgical Intensive Care Unit Patients: A Comparative Study
by Lyuboslav Katov, Jessica Gierak, Yannick Teumer, Federica Diofano, Carlo Bothner, Wolfgang Rottbauer and Karolina Weinmann-Emhardt
Medicina 2025, 61(9), 1703; https://doi.org/10.3390/medicina61091703 - 19 Sep 2025
Viewed by 1128
Abstract
Background and Objectives: Atrial fibrillation (AF) in critically ill patients (CIP) is associated with worse outcomes and increased mortality in the intensive care unit (ICU). Rhythm control strategies are often unfeasible due to underlying comorbidities, making rate control the preferred initial approach. However, [...] Read more.
Background and Objectives: Atrial fibrillation (AF) in critically ill patients (CIP) is associated with worse outcomes and increased mortality in the intensive care unit (ICU). Rhythm control strategies are often unfeasible due to underlying comorbidities, making rate control the preferred initial approach. However, conventional beta-blockers may worsen hemodynamics through negative inotropic effects and peripheral vasodilation. Landiolol, an ultra-short-acting adrenoreceptor antagonist, may offer an alternative due to its high β1-cardioselectivity and minimal blood pressure (BP) impact. This study evaluated the efficacy and feasibility of landiolol in hemodynamically unstable CIP with tachyarrhythmia, used as add-on therapy after failure of standard treatments. Materials and Methods: Ten CIP, admitted for non-postoperative reasons, were prospectively enrolled for landiolol treatment (L-group) in the ICU of Ulm University Heart Center between July and December 2017. The control group contained 41 patients who had received standard therapy without landiolol (NL-group). The primary composite endpoint was defined as heart rate (HR) reduction while maintaining mean arterial pressure (MAP) above 65 mmHg. Results: The most frequent reason for ICU admission was hemodynamic instability related to tachyarrhythmia in patients with cardiogenic or septic shock. At therapy initiation, all patients exhibited a compromised hemodynamic status, with a median MAP of 68.0 (IQR 60.0–80.0) mmHg and a median HR of 160.0 (IQR 144.0–176.0) bpm. After a three-hour observation period, no significant differences in BP values were observed between the groups. The primary composite endpoint was achieved at comparable rates in both groups (p = 0.525). However, patients in the L-group achieved a greater reduction in HR compared to those in the NL-group (25.3% vs. 21.9%, p < 0.001). Conclusions: Landiolol achieved more effective HR control than standard therapy without adversely affecting BP stability. These findings suggest that landiolol may be a feasible and effective option for HR control in ICU CIP. Full article
(This article belongs to the Section Cardiology)
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39 pages, 1111 KB  
Review
Comprehensive Profiling of Cytokines and Growth Factors: Pathogenic Roles and Clinical Applications in Autoimmune Diseases
by Anna Donniacuo, Arianna Mauro, Chiara Cardamone, Anna Basile, Paola Manzo, Jelena Dimitrov, Anna Lisa Cammarota, Liberato Marzullo, Massimo Triggiani, Maria Caterina Turco, Margot De Marco and Alessandra Rosati
Int. J. Mol. Sci. 2025, 26(18), 8921; https://doi.org/10.3390/ijms26188921 - 13 Sep 2025
Viewed by 776
Abstract
Autoimmune diseases are characterized by dysregulated adaptive immune responses leading to chronic inflammation and tissue damage. Cytokines and growth factors play central roles in modulating immune regulation, inflammation, and tissue repair, thereby representing critical biomarkers for the enhancement of diagnosis, prognosis, and therapeutic [...] Read more.
Autoimmune diseases are characterized by dysregulated adaptive immune responses leading to chronic inflammation and tissue damage. Cytokines and growth factors play central roles in modulating immune regulation, inflammation, and tissue repair, thereby representing critical biomarkers for the enhancement of diagnosis, prognosis, and therapeutic monitoring. This review provides a comprehensive overview of pro-inflammatory and anti-inflammatory cytokines, as well as growth factors, emphasizing their pathogenic roles and clinical relevance across various autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and connective tissue diseases such as systemic sclerosis, Sjögren’s syndrome, and systemic lupus erythematosus. Key pro-inflammatory cytokines—such as TNF-α, IL-1β, IL-6, IL-17, and IFN-γ—are examined regarding their contributions to disease progression and activity, alongside anti-inflammatory cytokines like IL-10 and IL-4, which regulate immune tolerance and inflammation resolution. Growth factors, such as TGF-β, are analyzed for their dual roles in immune modulation, fibrosis, and tissue remodeling. Cytokine signature profiles employed as diagnostic tools are discussed, together with the need for assay standardization. Advances in multiplex and omics technologies facilitating biomarker discovery are also reviewed. Finally, current and emerging therapeutic strategies targeting cytokines and growth factors, such as anti-TNF agents, IL inhibitors, anti-interferon therapies, and JAK/STAT pathway blockers, are explored. Full article
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29 pages, 1471 KB  
Review
Targeting the cGAS-STING Pathway to Modulate Immune Inflammation in Diabetes and Cardiovascular Complications: Mechanisms and Therapeutic Insights
by Guida Cai, Xi Zhang, Jiexi Jiao, Weijie Du and Meiling Yan
Curr. Issues Mol. Biol. 2025, 47(9), 750; https://doi.org/10.3390/cimb47090750 - 12 Sep 2025
Viewed by 964
Abstract
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and chronic hyperglycemia, markedly increases the incidence and mortality of cardiovascular disease (CVD). Emerging preclinical evidence identifies the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) pathway as a critical mediator of diabetic cardiovascular inflammation. [...] Read more.
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and chronic hyperglycemia, markedly increases the incidence and mortality of cardiovascular disease (CVD). Emerging preclinical evidence identifies the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) pathway as a critical mediator of diabetic cardiovascular inflammation. Metabolic stressors in T2DM—hyperglycemia, lipotoxicity, and mitochondrial dysfunction—induce leakage of mitochondrial and microbial double-stranded DNA into the cytosol, where it engages cGAS and activates STING. Subsequent TBK1/IRF3 and NF-κB signaling drives low-grade inflammation across cardiomyocytes, endothelial cells, macrophages, and fibroblasts. Genetic deletion of cGAS or STING in high-fat-diet-fed diabetic mice reduces NLRP3 inflammasome-mediated pyroptosis, limits atherosclerotic lesion formation, and preserves cardiac contractile performance. Pharmacological inhibitors, including RU.521 (cGAS antagonist), C-176/H-151 (STING palmitoylation blockers), and the TBK1 inhibitor amlexanox, effectively lower pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and improve left ventricular ejection fraction in diabetic cardiomyopathy and ischemia–reperfusion injury models. Novel PROTAC degraders targeting cGAS/STING and natural products such as Astragaloside IV and Tanshinone IIA further support the pathway’s druggability. Collectively, these findings position the cGAS–STING axis as a central molecular nexus linking metabolic derangement to cardiovascular pathology in T2DM and underscore its inhibition or targeted degradation as a promising dual cardiometabolic therapeutic strategy. Full article
(This article belongs to the Section Molecular Pharmacology)
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21 pages, 1918 KB  
Review
The Therapeutic Potential of Propranolol and Other Beta-Blockers in Hyperthyroidism
by Weronika Szybiak-Skora, Miłosz Miedziaszczyk, Edyta Szałek and Katarzyna Lacka
Int. J. Mol. Sci. 2025, 26(17), 8322; https://doi.org/10.3390/ijms26178322 - 27 Aug 2025
Viewed by 2211
Abstract
β-blockers have found wide application in cardiology, neurology, psychiatry, anaesthesiology, and endocrinology. Due to the reduction in excessive reactivity of the peripheral sympathetic nervous system, they have been used in the treatment of symptoms of hyperthyroidism. Significant efficacy in alleviating neuro-psychiatric symptoms associated [...] Read more.
β-blockers have found wide application in cardiology, neurology, psychiatry, anaesthesiology, and endocrinology. Due to the reduction in excessive reactivity of the peripheral sympathetic nervous system, they have been used in the treatment of symptoms of hyperthyroidism. Significant efficacy in alleviating neuro-psychiatric symptoms associated with hyperthyroidism is attributed to propranolol, while cardiac symptoms are alleviated by both non-selective and cardioselective β-blockers. The aim of our study is to collect and summarise the existing knowledge on the role of β-blockers in patients with hyperthyroidism, with particular emphasis on pregnant patients, the group with iatrogenic hyperthyroidism, and patients after amiodarone. Due to their favourable safety profile, they appear to be a beneficial supplementary therapy to the treatment of hyperthyroidism in pregnant patients. β-blockers are also used in the treatment of complications of hyperthyroidism after amiodarone administration. They may influence the therapeutic process of amiodarone-induced hyperthyroidism itself, as well as being a therapeutic alternative to amiodarone in a cardiovascular context. By alleviating the symptoms associated with high doses of L-thyroxine, which are used, e.g., in. patients with thyroid cancer, β-blockers may make it possible to maintain low TSH values. Full article
(This article belongs to the Special Issue Molecular Biology of the Thyroid Cancer and Thyroid Dysfunctions)
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19 pages, 3496 KB  
Article
Sulbactam: A β–Lactam Compound with Neuroprotective Effects in Epilepsy
by Fang-Chia Chang, Chiung-Hui Liu, Wen-Chieh Liao, Yu-Shiuan Tzeng, Ru-Yin Tsai, Li-Ho Tseng, Ching-Sui Hung, Shey-Lin Wu and Ying-Jui Ho
Neurol. Int. 2025, 17(9), 135; https://doi.org/10.3390/neurolint17090135 - 27 Aug 2025
Viewed by 1158
Abstract
Background: The pathophysiology of epilepsy is characterized by increased neuronal activity due to an excess of the excitatory neurotransmitter glutamate and a deficiency in the inhibitory neurotransmitter gamma–aminobutyric acid (GABA). Epilepsy presents with seizures, neuronal loss, and hyperactivity in the subthalamic nucleus (STN). [...] Read more.
Background: The pathophysiology of epilepsy is characterized by increased neuronal activity due to an excess of the excitatory neurotransmitter glutamate and a deficiency in the inhibitory neurotransmitter gamma–aminobutyric acid (GABA). Epilepsy presents with seizures, neuronal loss, and hyperactivity in the subthalamic nucleus (STN). Astrocytes play a crucial role by absorbing extracellular glutamate through glutamate transporter–1 (GLT–1), thereby reducing neuronal excitation. Upregulating the expression of astrocytic GLT–1 is a promising therapeutic strategy for epilepsy. Sulbactam (SUL), a β–lactam antibiotic, has been demonstrated to exert neuroprotective effects by upregulating GLT–1 expression. Objectives: This study investigated the impact of SUL on neuronal and behavioral changes in epilepsy by using a pentylenetetrazol (PTZ)-induced rat model of epilepsy. Methods: Rats were treated with saline, SUL (50 and 150 mg/kg), or a combination of SUL and the GLT–1 blocker dihydrokainate (DHK) for 20 days. Subsequently, behavioral tasks were conducted to assess recognition, anxiety, and memory. Results: Histological analyses revealed that SUL ameliorated neuronal deficits, increased astrocytic GLT–1 expression, and reduced hyperactivity in the STN. Additionally, SUL promoted astrocyte proliferation, indicating a new dimension of its neuroprotective properties. However, the beneficial effects of SUL were prevented by DHK. Conclusions: This pioneering study highlights multiple benefits of SUL, including seizure suppression, increased GLT–1 expression, and astrocyte proliferation, underscoring its high potential as a treatment for epilepsy. Full article
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28 pages, 1506 KB  
Review
The Heart–Brain Axis in the Artificial Intelligence Era: Integrating Old and New Insights Towards New Targeting and Innovative Neuro- and Cardio-Therapeutics
by Andreas Palantzas and Maria Anagnostouli
Int. J. Mol. Sci. 2025, 26(17), 8217; https://doi.org/10.3390/ijms26178217 - 24 Aug 2025
Viewed by 1775
Abstract
The heart–brain axis (HBA) is a dynamic system of reciprocal communication between the cardiovascular and central nervous system, incorporating neural, immunologic, molecular and hormonal pathways. The central autonomic network is described as a key regulator of cardiovascular activity and autonomic dysfunction as an [...] Read more.
The heart–brain axis (HBA) is a dynamic system of reciprocal communication between the cardiovascular and central nervous system, incorporating neural, immunologic, molecular and hormonal pathways. The central autonomic network is described as a key regulator of cardiovascular activity and autonomic dysfunction as an important mechanism underlying various neurologic and cardiac disorders. Heart rate variability (HRV) is identified as the key biomarker of the axis reflecting autonomic nervous system balance. Increased understanding of its molecular mechanisms has led to the proposal of new therapeutic strategies focused on modulating heart–brain communication including β-blockers, vagus nerve stimulation, neurotrophin modulation, and nanoparticle-based approaches. The integration of wearables and artificial intelligence (AI) has allowed for real-time monitoring and innovative diagnostic and prognostic applications. The present narrative review summarizes current knowledge on the mechanisms comprising the heart–brain axis, their implication in neurologic and cardiac disorders, and their potential for developing novel therapies. It also highlights how advancements in wearable technology and AI systems are being integrated into clinical practice and transforming the landscape. Full article
(This article belongs to the Special Issue From Molecular Insights to Novel Therapies: Neurological Diseases)
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14 pages, 14654 KB  
Article
Monitoring Beta-Blocker Therapy in Adolescents with Exercise-Induced Intraventricular Gradients Using Exercise Stress Echocardiography
by Nuno Cotrim, Hugo M. Café, Jorge Guardado, Pedro Cordeiro, Rui Martins, Hortense Cotrim and Carlos Cotrim
Biomedicines 2025, 13(8), 2035; https://doi.org/10.3390/biomedicines13082035 - 21 Aug 2025
Viewed by 577
Abstract
Background: Treadmill exercise stress echocardiography (ESE) is both feasible and safe in the pediatric population. Although regional wall motion abnormalities (RWMAs) have limited diagnostic utility, Doppler studies frequently demonstrate significant intraventricular pressure gradients (IVPGs) during exercise. These IVPGs, which were observed in 39% [...] Read more.
Background: Treadmill exercise stress echocardiography (ESE) is both feasible and safe in the pediatric population. Although regional wall motion abnormalities (RWMAs) have limited diagnostic utility, Doppler studies frequently demonstrate significant intraventricular pressure gradients (IVPGs) during exercise. These IVPGs, which were observed in 39% of 258 previously studied adolescents, are absent at rest. Their detection provides valuable insight into exercise-related symptoms and abnormal findings on resting or stress electrocardiograms (ECGs). Purpose: To evaluate the effect of β-blocker therapy on the occurrence of intraventricular pressure gradients (IVPGs) in adolescents presenting with symptoms or abnormal findings on resting or stress electrocardiograms (ECGs). Methods: Exercise stress echocardiography (ESE) was repeated in 66 of 101 adolescents who were found to have developed intraventricular pressure gradients (IVPGs) during the initial assessment. All participants had normal resting echocardiograms, and all underwent follow-up evaluation while receiving β-blocker therapy. The study cohort included 15 females (23%) and the mean age of participants was 14.6 ± 1.7 years (range: 11–17 years). Comprehensive two-dimensional and Doppler echocardiographic assessments were performed at baseline and during β-blocker treatment. Results: During the initial ESE, the mean intraventricular pressure gradient (IVPG) was 105 ± 38 mmHg. Under β-blocker therapy, 37 adolescents no longer developed IVPGs while, in the remaining 29 adolescents, the IVPG was significantly reduced to a mean of 58 ± 32 mmHg (p < 0.0001). The mean heart rate at peak exercise decreased from 178 ± 15 bpm at baseline to 157 ± 9 bpm during the repeat ESE under β-blocker treatment (p < 0.0001). Clinical symptoms were reproduced in forty-seven adolescents during the initial ESE, but occurred in only seven adolescents during treatment (p < 0.0001). Conclusions: In adolescents presenting with symptoms or abnormal resting or stress ECG findings, and exertional intraventricular pressure gradients (IVPGs), oral β-blocker therapy either prevented the occurrence of IVPGs or significantly reduced their severity. These hemodynamic improvements were associated with the resolution of clinical symptoms in 85% of the symptomatic cohort. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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21 pages, 6069 KB  
Article
Novel Neuroactive Steroid Analogs and Voltage-Dependent Blockers of CaV3.2 Currents, B372 and YX23, Are Effective Anti-Nociceptives with Diminished Sedative Properties in Intact Female Mice
by Benjamin Volvovitz, Rakib Miah, Kibeom Park, Jae Hun Kim, Raul Vargas, Yuanjiang Xu, Mingxing Qian, Douglas F. Covey, Slobodan M. Todorovic and Vesna Jevtovic-Todorovic
Biomolecules 2025, 15(8), 1175; https://doi.org/10.3390/biom15081175 - 16 Aug 2025
Viewed by 615
Abstract
Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel [...] Read more.
Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies. Low-voltage activated (T-type) calcium channels (CaV3.2 isoform) could be a promising therapeutic target for the development of novel pain therapies. Indeed, our published findings suggest that novel neuroactive steroid (NAS) analogs that modulate the activity of CaV3.2 channels have unique anti-nociceptive properties. However, the concern with current NASs appears to be their hypnotic/sedative properties, thus potentially hindering the future development of NASs for novel pain therapies. Hence, we developed a new line of NASs that are effective blockers of neuronal CaV3.2 channels in pain pathways while having more favorable pharmacodynamic properties, i.e., lack of sedative/hypnotic side effects. We present two promising novel analogs of NASs—B372 ((3β,5α,17β)-3-Hydroxyandrostan-17-carbonitrile) and YX23 ((3β,5α,17β)-3-Methoxyestran-17-ol). Using an in vitro approach, we show that B372 and YX23 are effective in blocking CaV3.2 channels. Using an in vivo approach, we show that they are effective anti-nociceptives in wild-type but not CaV3.2 knock-out mice. Importantly, we show that they lack sedative/hypnotic effects. Full article
(This article belongs to the Special Issue Role of Neuroactive Steroids in Health and Disease: 2nd Edition)
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18 pages, 1120 KB  
Article
Quantification of Acetaminophen, Ibuprofen, and β-Blockers in Wastewater and River Water Bodies During the COVID-19 Pandemic
by Neliswa Mpayipheli, Anele Mpupa, Ntakadzeni Edwin Madala and Philiswa Nosizo Nomngongo
Environments 2025, 12(8), 278; https://doi.org/10.3390/environments12080278 - 12 Aug 2025
Viewed by 1905
Abstract
The consumption of pharmaceuticals during the COVID-19 pandemic increased significantly. As such, over-the-counter drugs such as acetaminophen (ACT), ibuprofen (IBU), metoprolol (MET), and propranolol (PRO) were among the pharmaceuticals that were widely used to contain COVID-19 symptoms. Therefore, this study investigated the occurrence [...] Read more.
The consumption of pharmaceuticals during the COVID-19 pandemic increased significantly. As such, over-the-counter drugs such as acetaminophen (ACT), ibuprofen (IBU), metoprolol (MET), and propranolol (PRO) were among the pharmaceuticals that were widely used to contain COVID-19 symptoms. Therefore, this study investigated the occurrence of ACT, IBU, MET, and PRO in wastewater and river water systems, focusing on two provinces in South Africa (Gauteng (GP) and KwaZulu-Natal (KZN)). Generally, WWTP influents had the highest concentrations in both provinces. ACT, MET, and PRO were frequently detected compared to ibuprofen, particularly in KZN, during the second wave of the COVID-19 pandemic. However, a low detection occurred during the fourth wave of the COVID-19 pandemic. The concentrations of ACT, IBU, MET, and PRO in influent wastewater samples ranged from ND-480 µg/L, ND-54.1 µg/L, ND-52.8 µg/L, to ND-13.1 µg/L, respectively. In comparison with influent samples, ACT, IBU, MET, and PRO concentrations of effluent wastewater samples were generally at lower concentration levels: ACT (ND-289 µg/L), IBU (ND-36.1 µg/L), MET (ND-13.9 µg/L), and PRO (ND-5.53 µg/L). The removal efficiencies of the selected pharmaceuticals in KZN WWTPs ranged from 6.1 to 100% and −362.6 to 100% in the GP province. The ecological risk assessment results showed a low to high ecological risk against fish, Daphnia magna, and algae due to the presence of these pharmaceuticals. Full article
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31 pages, 4843 KB  
Review
Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets
by Uttapol Permpoon, Jiyeong Moon, Chul Young Kim and Tae-gyu Nam
Int. J. Mol. Sci. 2025, 26(15), 7616; https://doi.org/10.3390/ijms26157616 - 6 Aug 2025
Cited by 1 | Viewed by 2537
Abstract
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose [...] Read more.
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
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24 pages, 2475 KB  
Article
An Immunomodulating Peptide with Potential to Promote Anticancer Immunity Without Compromising Immune Tolerance
by Michael Agrez, Christopher Chandler, Amanda L. Johnson, Marlena Sorensen, Kirstin Cho, Stephen Parker, Benjamin Blyth, Darryl Turner, Justyna Rzepecka, Gavin Knox, Anastasia Nika, Andrew M. Hall, Hayley Gooding and Laura Gallagher
Biomedicines 2025, 13(8), 1908; https://doi.org/10.3390/biomedicines13081908 - 5 Aug 2025
Viewed by 817
Abstract
Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the [...] Read more.
Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article
(This article belongs to the Special Issue Peptides and Amino Acids in Drug Development: Here and Now)
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46 pages, 2713 KB  
Article
Anti-Inflammatory and Antiplatelet Interactions on PAF and ADP Pathways of NSAIDs, Analgesic and Antihypertensive Drugs for Cardioprotection—In Vitro Assessment in Human Platelets
by Makrina Katsanopoulou, Zisis Zannas, Anna Ofrydopoulou, Chatzikamari Maria, Xenophon Krokidis, Dimitra A. Lambropoulou and Alexandros Tsoupras
Medicina 2025, 61(8), 1413; https://doi.org/10.3390/medicina61081413 - 4 Aug 2025
Viewed by 1643
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 707 KB  
Review
The Role of Landiolol in Coronary Artery Disease: Insights into Acute Coronary Syndromes, Stable Coronary Artery Disease and Computed Tomography Coronary Angiography
by Athina Nasoufidou, Marios G. Bantidos, Panagiotis Stachteas, Dimitrios V. Moysidis, Andreas Mitsis, Barbara Fyntanidou, Konstantinos Kouskouras, Efstratios Karagiannidis, Theodoros Karamitsos, George Kassimis and Nikolaos Fragakis
J. Clin. Med. 2025, 14(15), 5216; https://doi.org/10.3390/jcm14155216 - 23 Jul 2025
Viewed by 734
Abstract
Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. [...] Read more.
Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article
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