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21 pages, 546 KiB  
Review
The Inflammatory Bridge Between Type 2 Diabetes and Neurodegeneration: A Molecular Perspective
by Housem Kacem, Michele d’Angelo, Elvira Qosja, Skender Topi, Vanessa Castelli and Annamaria Cimini
Int. J. Mol. Sci. 2025, 26(15), 7566; https://doi.org/10.3390/ijms26157566 (registering DOI) - 5 Aug 2025
Abstract
Chronic low-grade inflammation is a hallmark of both metabolic and neurodegenerative diseases. In recent years, several studies have highlighted the pivotal role of systemic metabolic dysfunction, particularly insulin resistance, in shaping neuroinflammatory processes and contributing to impaired cognitive performance. Among metabolic disorders, type [...] Read more.
Chronic low-grade inflammation is a hallmark of both metabolic and neurodegenerative diseases. In recent years, several studies have highlighted the pivotal role of systemic metabolic dysfunction, particularly insulin resistance, in shaping neuroinflammatory processes and contributing to impaired cognitive performance. Among metabolic disorders, type 2 diabetes mellitus has emerged as a major risk factor for the development of age-related neurodegenerative conditions, suggesting a complex and bidirectional crosstalk between peripheral metabolic imbalance and central nervous system function. This review aims to explore the cellular and molecular mechanisms underlying the interaction between metabolic dysregulation and brain inflammation. By integrating current findings from endocrinology, immunology, and neuroscience, this work provides a comprehensive overview of how chronic metabolic inflammation may contribute to the onset and progression of neurodegenerative conditions. This interdisciplinary approach could offer novel insights into potential therapeutic strategies targeting both metabolic and neuroinflammatory pathways. Full article
(This article belongs to the Collection Latest Review Papers in Endocrinology and Metabolism)
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21 pages, 432 KiB  
Review
Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review
by Amalia Di Petrillo, Agnese Favale, Sara Onali, Amit Kumar, Giuseppe Abbracciavento and Massimo Claudio Fantini
J. Clin. Med. 2025, 14(15), 5522; https://doi.org/10.3390/jcm14155522 - 5 Aug 2025
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article
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21 pages, 668 KiB  
Review
Diabetes and Sarcopenia: Metabolomic Signature of Pathogenic Pathways and Targeted Therapies
by Anamaria Andreea Danciu, Cornelia Bala, Georgeta Inceu, Camelia Larisa Vonica, Adriana Rusu, Gabriela Roman and Dana Mihaela Ciobanu
Int. J. Mol. Sci. 2025, 26(15), 7574; https://doi.org/10.3390/ijms26157574 (registering DOI) - 5 Aug 2025
Abstract
Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative [...] Read more.
Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article
35 pages, 1184 KiB  
Review
Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise
by Angela Falvino, Roberto Bonanni, Umberto Tarantino, Virginia Tancredi and Ida Cariati
Int. J. Mol. Sci. 2025, 26(15), 7573; https://doi.org/10.3390/ijms26157573 (registering DOI) - 5 Aug 2025
Abstract
Aging is a complex physiological process that profoundly affects the functionality of the musculoskeletal system, contributing to an increase in the incidence of diseases such as osteoporosis, osteoarthritis, and sarcopenia. Cellular senescence plays a crucial role in these degenerative processes, promoting chronic inflammation [...] Read more.
Aging is a complex physiological process that profoundly affects the functionality of the musculoskeletal system, contributing to an increase in the incidence of diseases such as osteoporosis, osteoarthritis, and sarcopenia. Cellular senescence plays a crucial role in these degenerative processes, promoting chronic inflammation and tissue dysfunction through the senescence-associated secretory phenotype (SASP). Recently, senotherapeutics have shown promising results in improving musculoskeletal health. Natural compounds such as resveratrol, rapamycin, quercetin, curcumin, vitamin E, genistein, fisetin, and epicatechin act on key signaling pathways, offering protective effects against musculoskeletal decline. On the other hand, molecules such as dasatinib, navitoclax, UBX0101, panobinostat, and metformin have been shown to be effective in eliminating or modulating senescent cells. However, understanding the mechanisms of action, long-term safety, and bioavailability remain areas for further investigation. In this context, physical exercise emerges as an effective non-pharmacological countermeasure, capable of directly modulating cellular senescence and promoting tissue regeneration, representing an integrated strategy to combat age-related diseases. Therefore, we have provided an overview of the main anti-aging compounds and examined the potential of physical exercise as a strategy in the management of age-related musculoskeletal disorders. Further studies should focus on identifying synergistic combinations of pharmacological and non-pharmacological interventions to optimize the effectiveness of anti-aging strategies and promoting healthier musculoskeletal aging. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence and Anti-Aging Strategies)
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17 pages, 1027 KiB  
Review
Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives
by Maria Kourti, Paschalis Evangelidis, Emmanuel Roilides and Elias Iosifidis
Pathogens 2025, 14(8), 774; https://doi.org/10.3390/pathogens14080774 (registering DOI) - 5 Aug 2025
Abstract
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and [...] Read more.
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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20 pages, 1545 KiB  
Review
Nanomedicine as a Promising Treatment Approach for Obesity
by Abeer Alanazi, Alexander Craven, Spiridon V. Spirou, Maria Jose Santos-Martinez, Carlos Medina and Oliviero L. Gobbo
J. Nanotheranostics 2025, 6(3), 21; https://doi.org/10.3390/jnt6030021 - 5 Aug 2025
Abstract
Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by [...] Read more.
Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article
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27 pages, 2559 KiB  
Review
Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review
by Debalina Bose, Adetayo Olorunlana, Rania Abdel-Latif, Ademola C. Famurewa and Eman M. Othman
J. Xenobiot. 2025, 15(4), 126; https://doi.org/10.3390/jox15040126 - 5 Aug 2025
Abstract
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty [...] Read more.
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article
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15 pages, 787 KiB  
Review
Bradykinin Receptors in Metabolic Disorders: A Comprehensive Review
by Jéssica Branquinho, Raquel Leão Neves, Michael Bader and João Bosco Pesquero
Drugs Drug Candidates 2025, 4(3), 37; https://doi.org/10.3390/ddc4030037 - 5 Aug 2025
Abstract
The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the [...] Read more.
The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article
(This article belongs to the Special Issue Drugs of the Kallikrein-Kinin System)
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34 pages, 640 KiB  
Review
Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches
by Giuseppe Marano, Francesco Maria Lisci, Gianluca Boggio, Ester Maria Marzo, Francesca Abate, Greta Sfratta, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, Eleonora Gaetani and Marianna Mazza
Future Pharmacol. 2025, 5(3), 42; https://doi.org/10.3390/futurepharmacol5030042 - 4 Aug 2025
Abstract
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse [...] Read more.
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article
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22 pages, 2139 KiB  
Review
New Perspectives on Nutraceutical Insulin Sensitizing Agents in the Treatment of Psoriasis and Other Dermatological Diseases
by Pietro Morrone, Francesca Caroppo, Alberto De Pedrini, Alessandro Colletti and Germano Baj
Int. J. Mol. Sci. 2025, 26(15), 7538; https://doi.org/10.3390/ijms26157538 (registering DOI) - 4 Aug 2025
Abstract
Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review [...] Read more.
Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article
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16 pages, 875 KiB  
Review
Cardiorenal Syndrome in the Elderly: Challenges and Considerations
by Matthew Jarocki, Sophie Green, Henry H. L. Wu and Rajkumar Chinnadurai
Geriatrics 2025, 10(4), 104; https://doi.org/10.3390/geriatrics10040104 - 4 Aug 2025
Abstract
Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due [...] Read more.
Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article
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28 pages, 2414 KiB  
Review
Breaking Down Osteoarthritis: Exploring Inflammatory and Mechanical Signaling Pathways
by Wafa Ali Batarfi, Mohd Heikal Mohd Yunus, Adila A. Hamid, Manira Maarof and Rizal Abdul Rani
Life 2025, 15(8), 1238; https://doi.org/10.3390/life15081238 - 4 Aug 2025
Abstract
Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the [...] Read more.
Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 3rd Edition)
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14 pages, 286 KiB  
Hypothesis
Botulinum Toxin-A, Generating a Hypothesis for Orofacial Pain Therapy
by Yair Sharav, Rafael Benoliel and Yaron Haviv
Toxins 2025, 17(8), 389; https://doi.org/10.3390/toxins17080389 - 4 Aug 2025
Abstract
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require [...] Read more.
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article
15 pages, 967 KiB  
Article
Biomarker Correlations in PTSD: IL-18, IRE1, pERK, and ATF6 via Courtauld Emotional Control Scale (CECS)
by Izabela Woźny-Rasała and Ewa Alicja Ogłodek
Int. J. Mol. Sci. 2025, 26(15), 7506; https://doi.org/10.3390/ijms26157506 (registering DOI) - 3 Aug 2025
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Abstract
Post-traumatic stress disorder (PTSD) is a chronic mental health condition resulting from exposure to traumatic events. It is associated with long-term neurobiological changes and disturbances in emotional regulation. Understanding the sociodemographic profiles, biomarkers, and emotional control in patients with PTSD helps to better [...] Read more.
Post-traumatic stress disorder (PTSD) is a chronic mental health condition resulting from exposure to traumatic events. It is associated with long-term neurobiological changes and disturbances in emotional regulation. Understanding the sociodemographic profiles, biomarkers, and emotional control in patients with PTSD helps to better comprehend the impact of the disorder on the body and its clinical course. An analysis of biomarkers such as Interleukin-18 (IL-18), Inositol-Requiring Enzyme 1 (IRE1), Phosphorylated Extracellular Signal-Regulated Kinase (pERK), and Activating Transcription Factor–6 (ATF-6) in PTSD patients with varying durations of illness (≤5 years and >5 years) and a control group without PTSD revealed significant differences. Patients with recently diagnosed PTSD (≤5 years) showed markedly elevated levels of inflammatory and cellular stress markers, indicating an intense neuroinflammatory response during the acute phase of the disorder. In the chronic PTSD group (>5 years), the levels of these biomarkers were lower than in the recently diagnosed group, but still significantly higher than in the control group. An opposite trend was observed regarding the suppression of negative emotions, as measured by the Courtauld Emotional Control Scale (CECS): individuals with chronic PTSD exhibited a significantly greater suppression of anger, depression, and anxiety than those with recent PTSD or healthy controls. Correlations between biomarkers were strongest in individuals with chronic PTSD, suggesting a persistent neuroinflammatory dysfunction. However, the relationships between biomarkers and emotional suppression varied depending on the stage of PTSD. These findings highlight the critical role of PTSD duration in shaping the neurobiological and emotional mechanisms of the disorder, which may have important implications for therapeutic strategies and patient monitoring. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 2044 KiB  
Review
Histopathological and Molecular Insights into Chronic Nasopharyngeal and Otic Disorders in Children: Structural and Immune Mechanisms Underlying Disease Chronicity
by Diana Szekely, Flavia Zara, Raul Patrascu, Cristina Stefania Dumitru, Dorin Novacescu, Alexia Manole, Carmen Aurelia Mogoanta, Dan Iovanescu and Gheorghe Iovanescu
Life 2025, 15(8), 1228; https://doi.org/10.3390/life15081228 - 3 Aug 2025
Viewed by 58
Abstract
Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular [...] Read more.
Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article
(This article belongs to the Special Issue New Trends in Otorhinolaryngology)
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