Pathophysiology : the official journal of the International Society for Pathophysiology最新文献

{"title":"Peri-Injury Stearidonic Acid Ethanolamide Modulates Astroglial Reactivity-Associated Markers in a Mouse Model of Mild Traumatic Brain Injury.","authors":"Anastasia Girich, Igor Manzhulo, Darya Ivashkevich, Arina Ponomarenko, Anna Tyrtyshnaia","doi":"10.3390/pathophysiology33040078","DOIUrl":"https://doi.org/10.3390/pathophysiology33040078","url":null,"abstract":"<p><strong>Background/objectives: </strong>Mild traumatic brain injury (mTBI) can cause persistent neuroinflammation and astroglial reactivity. This study examined whether peri-injury administration of stearidonic acid ethanolamide (SDEA) was associated with changes in astrocyte-associated responses after mTBI and in primary astroglial cultures.</p><p><strong>Methods: </strong>Male C57BL/6 mice received SDEA (10 mg/kg, subcutaneously) for 2 days before mTBI, immediately after injury, and for 7 days thereafter. At 11 weeks post-injury, cortical GFAP immunoreactivity and the expression of astrocyte-associated markers, PPAR isoforms, and neurotrophic factors were assessed by immunohistochemistry and RT-qPCR. Primary astroglial cultures were treated with 1 or 10 μM SDEA for 48 h.</p><p><strong>Results: </strong>SDEA attenuated mTBI-associated increases in GFAP-positive cells and cortical <i>Gfap</i> and <i>C3</i> expression while increasing <i>S100a10</i> and <i>Clcf1</i> expression. SDEA treatment was accompanied by increased cortical <i>Ppara</i> and <i>Pparg</i> mRNA expression and changes in the expression of neurotrophic-factor genes. In cultured astroglia, SDEA increased <i>S100a10</i>, <i>Clcf1</i>, <i>Ppara</i>, <i>Pparg</i>, <i>Bdnf</i>, <i>Ngf</i>, and <i>Gdnf</i> mRNA expression without significantly altering <i>Gfap</i> or <i>C3</i>.</p><p><strong>Conclusions: </strong>Peri-injury SDEA administration was associated with reduced chronic cortical GFAP reactivity and changes in selected astrocyte-associated transcripts after mTBI.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central Neural Circuits Underlying Stress-Associated Bowel Disorders.","authors":"Natsufu Yuki, Tomoya Sawamura, Takahiko Shiina, Yasutake Shimizu","doi":"10.3390/pathophysiology33040077","DOIUrl":"https://doi.org/10.3390/pathophysiology33040077","url":null,"abstract":"<p><p>Psychological stress can cause or exacerbate irritable bowel syndrome (IBS). According to the Rome V framework, functional gastrointestinal disorders, including IBS, are classified as gut-brain interaction disorders. These disorders involve information processing by the central nervous system. Therefore, to understand IBS pathophysiology, it is necessary to focus on the central neural circuits regulating visceral sensation and colorectal motility. In this review, we first outline the autonomic outflow that controls the colorectum and then focus on descending neural pathways that modulate spinal visceral sensory processing and colorectal autonomic outflow, as well as the hypothalamic, midbrain, limbic, and cortical regions that regulate these processes. Finally, we outline their effects within the context of stress.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiological Mechanisms of UVB Irradiation in the Skin: Inflammation, Oxidative Stress and Neuroimmune Interactions.","authors":"Lucas Sobral de Rossi, Renata M Martinez, Geovana Martelossi-Cebinelli, Soraia Mendes-Pierotti, Willian H Chinen, Jonathan Ratko, Bianca Mattioli Trambaioli, Josiane A Vignoli, Sandra R Georgetti, Marcela M Baracat, Fabiana T M C Vicentini, Waldiceu A Verri, Rubia Casagrande","doi":"10.3390/pathophysiology33040076","DOIUrl":"https://doi.org/10.3390/pathophysiology33040076","url":null,"abstract":"<p><p>Ultraviolet B (UVB) irradiation, with wavelengths ranging from 290 to 320 nm, represents a biologically active fraction of solar irradiation that reaches the Earth's surface and exerts significant effects on human skin. Due to its high energy, UVB penetrates the epidermis and directly interacts with cellular components, particularly DNA, leading to the formation of photoproducts such as cyclobutane pyrimidine dimers. In parallel, UVB exposure induces the generation of reactive oxygen species, promoting oxidative stress and damage to lipids, proteins, and genetic material. These events activate key intracellular signaling pathways, including NF-κB and MAPKs, resulting in the production of pro-inflammatory mediators that amplify cutaneous inflammation. In addition to classical inflammatory and oxidative mechanisms, emerging evidence highlights the role of neuroimmune interactions in the skin, involving crosstalk between nerve endings, neuropeptides, and immune cells, which contributes to the regulation of local immune responses following UVB exposure. The integration of these processes plays a central role in the pathophysiology of UVB-induced skin damage and in the development of skin diseases. This review will discuss the molecular and cellular mechanisms underlying the cutaneous response triggered by UVB irradiation, with emphasis on inflammation, oxidative stress, and neuroimmune communication. Additionally, current and emerging therapeutic strategies based on pathophysiology mechanisms, including antioxidant agents, anti-inflammatory compounds, and photoprotective approaches, will be discussed to highlight potential avenues for improved prevention and treatment of UVB-induced skin damage.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of N-Acetylcysteine and Glycine Administration on Serum Levels of Soluble Suppressor of Tumorigenicity 2 and Cardiac Morphological Characteristics in an Animal Model of Streptozotocin-Induced Diabetes.","authors":"Malik Ejubović, Radivoj Jadrić, Sabaheta Hasić, Emina Kiseljaković, Lejla Alić, Esad Ćosović, Dina Kapić, Orhan Lepara, Amira Jagodić Ejubović, Almir Fajkić","doi":"10.3390/pathophysiology33040075","DOIUrl":"https://doi.org/10.3390/pathophysiology33040075","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives:&lt;/b&gt; Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus characterized by progressive myocardial remodeling driven by oxidative stress, inflammation, and fibrosis. The interleukin-33 (IL-33)/soluble suppression of tumorigenicity 2 (sST2) signaling axis has recently emerged as an important regulator of cardiac remodeling and a potential therapeutic target in DCM. N-acetylcysteine (NAC) and glycine exhibit complementary antioxidant and anti-inflammatory properties; however, their combined effects on circulating IL-33 and sST2 levels and myocardial structural remodeling in experimental diabetes remain insufficiently investigated. This study evaluated the effects of NAC and glycine, administered alone or in combination, on oxidative stress, inflammatory biomarkers, cardiac morphology, and serum sST2 levels in streptozotocin-induced diabetic rats. &lt;b&gt;Methods:&lt;/b&gt; Thirty-four adult Wistar rats were randomly assigned to five groups: healthy controls, untreated diabetic animals, diabetic animals treated with NAC (100 mg/kg/day), glycine (250 mg/kg/day), or combined NAC and glycine for 12 weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). Serum concentrations of sST2, IL-33, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were determined. Cardiac remodeling was evaluated by stereological and histopathological analyses. &lt;b&gt;Results&lt;/b&gt;: Experimental diabetes significantly increased serum sST2, IL-33, and MDA concentrations and induced marked myocardial remodeling characterized by expansion of the interstitial and perivascular compartments, increased connective tissue deposition, and reduced cardiomyocyte volume density. Both NAC and glycine significantly attenuated these biochemical and structural abnormalities compared with untreated diabetic animals. Treatment effects varied across outcomes. The combined NAC and glycine regimen was associated with particularly pronounced reductions in sST2 and IL-33 and with preservation of myocardial architecture, whereas the magnitude of improvement in oxidative stress markers differed between treatment groups. &lt;b&gt;Conclusions:&lt;/b&gt; NAC and glycine, administered either alone or in combination, attenuated several biochemical and structural alterations associated with streptozotocin-induced diabetes. The magnitude of these effects varied across the assessed outcomes, with the combined regimen showing particularly favorable effects on circulating sST2 and IL-33 levels and myocardial structural remodeling, while some oxidative stress parameters showed greater improvement with NAC monotherapy. These outcome-dependent effects highlight the potential complementary actions of NAC and glycine without implying uniform superiority of the combined regimen. Overall, these findings provide an experimental basis for further investigation of NAC- and glycine-based therapeutic approaches for diabetes-associated ","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and the Gut-Brain Axis: Bidirectional, Converging Mechanisms Linking Brain Health, Neuroinflammation, and Neurodegeneration.","authors":"Bryce Bowler, Abdul Rehman Nasir, Aldona Szewczyk, Sarah Ocanas, Archana Unnikrishnan, Claire Delpirou Nouh","doi":"10.3390/pathophysiology33040074","DOIUrl":"https://doi.org/10.3390/pathophysiology33040074","url":null,"abstract":"<p><p>Sleep and the gastrointestinal (GI) tract interact in a complex and reciprocal relationship, although the molecular and physiological pathways underlying this interaction remain only partially defined. Communication between the central (CNS) and enteric nervous systems (ENS) spans neural, immune, endocrine, and metabolic pathways, including vagal nerve signaling, the hypothalamic-pituitary-adrenal (HPA) axis, gut-resident microbiota, and circulating microbial metabolites, such as bile acids with neuroinflammatory or neurotransmitter activity. In this narrative review, we synthesize evidence from animal models, observational cohorts, and intervention trials to map this bidirectional axis, focusing on several underexamined modulatory mechanisms including the interaction between the gut microbiome and the glymphatic system, the brain's perivascular waste-clearance network, which is implicated in the removal of amyloid-β (Aβ) and tau in Alzheimer's disease; neuroendocrine regulation and sex-related differences in gut microbiome composition and sleep patterns, which may help explain the divergent neurodegenerative disease risks between men and women; and age-related parallel trajectories of microbiome senescence and sleep fragmentation in older adults. We discuss melatonin, cortisol, estrogen, and ghrelin as endocrine mediators linking circadian biology to gut physiology, and we consider how environmental and lifestyle factors further perturb this system. These mechanisms form an integrative framework of the gut-brain-sleep axis and highlight priority directions for mechanistic and translational research, including significant nodes in this pathway where targeted interventions may help cognitive resilience and slow the neurodegenerative disease progression. More research clarifying these mechanisms may help identify the most promising targets, potentially leading to personalized, precision-medicine-based therapeutic strategies.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coronary Microvascular Dysfunction in ANOCA and INOCA: From Pathophysiological Endotypes to Precision Diagnosis and Treatment.","authors":"Aladin Altic, Nikola Jovanovic, Haris Džinić, Ashwin Ragupathi, Franco Joaquin Cossettini, Anida Šehanović, Marko Baralic, Aleksandar Sič","doi":"10.3390/pathophysiology33040073","DOIUrl":"https://doi.org/10.3390/pathophysiology33040073","url":null,"abstract":"<p><p>Coronary microvascular dysfunction (CMD) is an important cause of angina and myocardial ischemia in patients without obstructive coronary artery disease and contributes substantially to the clinical spectrum of angina with non-obstructive coronary arteries (ANOCA) and ischemia with non-obstructive coronary arteries (INOCA). These conditions represent a heterogeneous group of coronary vasomotor disorders in which structural and functional abnormalities of the coronary microcirculation, endothelial dysfunction, coronary vasospasm, and diffuse non-obstructive atherosclerosis may occur alone or in combination. This review summarizes current knowledge on the pathophysiology, diagnosis, and management of CMD in patients with ANOCA and INOCA. We discuss the distinction between ANOCA and INOCA, the principal coronary functional endotypes, and the mechanisms responsible for impaired coronary microvascular function. We also review contemporary diagnostic approaches, including non-invasive imaging and invasive coronary function testing, with emphasis on their complementary roles in identifying the underlying mechanism of ischemia. Current management strategies are presented from a mechanism-based perspective, including lifestyle modification, pharmacological therapy, endotype-guided treatment, and emerging therapeutic approaches. Improved understanding of coronary functional abnormalities has shifted clinical evaluation beyond the exclusion of obstructive coronary artery disease toward identification of the mechanism responsible for persistent symptoms and ischemia. Continued advances in disease phenotyping, coronary function testing, and targeted therapies are expected to support more individualized management and improve outcomes in this diverse patient population.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pheochromocytomas with Aggressive Histopathological Features Have Reduced Apelin and Increased VEGF Expression: Diagnostic and Prognostic Implications.","authors":"Hatice Çalışkan Burgucu, Tuğba Günler, Ethem Ömeroğlu, Yaşar Ünlü, Oğuzhan Aksu","doi":"10.3390/pathophysiology33040072","DOIUrl":"https://doi.org/10.3390/pathophysiology33040072","url":null,"abstract":"<p><p><b>Background:</b> Pheochromocytoma is a highly vascular neuroendocrine tumor with variable biological behavior. Reliable biomarkers reflecting tumor aggressiveness remain limited. This study evaluated apelin and vascular endothelial growth factor (VEGF) expression in pheochromocytoma and their associations with histopathological prognostic parameters. <b>Methods:</b> This retrospective single-center study included 20 pheochromocytoma patients and 18 normal adrenal medulla controls. Apelin and VEGF expression were evaluated immunohistochemically using the immunoreactivity score (IRS). Associations between IRS values and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score, Ki-67 index, tumor size, clinicopathological characteristics, and individual PASS components were analyzed. <b>Results:</b> Apelin IRS was significantly lower in pheochromocytoma than in normal adrenal medulla (median 0 vs. 4, <i>p</i> = 0.001), whereas VEGF IRS was significantly higher (median 6 vs. 2, <i>p</i> < 0.001). Tumors with PASS ≥ 4 had significantly lower apelin IRS than those with PASS < 4 (<i>p</i> = 0.001). Apelin IRS was inversely correlated with PASS (r = -0.874, <i>p</i> < 0.001), GAPP score (r = -0.618, <i>p</i> = 0.004), and Ki-67 (r = -0.560, <i>p</i> = 0.010). Lower apelin expression was also associated with diffuse growth pattern, central/confluent necrosis, and tumor cell spindling. VEGF IRS showed no significant association with PASS, GAPP score, Ki-67, tumor size, or individual PASS components. <b>Conclusions:</b> Reduced apelin immunoreactivity was associated with unfavorable histopathological features in pheochromocytoma, whereas increased VEGF immunoreactivity was not associated with the evaluated histopathological risk parameters. These exploratory findings suggest that apelin may be a candidate tissue marker; however, its clinical and prognostic relevance requires further investigation in larger multicenter studies.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Analysis of Bone Marrow IL-10 and Plasma IL-1RA in Acute Traumatic Versus Chronic Non-Traumatic Orthopedic Patients: A Prospective Observational Study.","authors":"Muriel Tahtouh Zaatar, Alex Kattoura, Bayan Aasar, Rima Othman, Souheil Hallit, Marc Karam, Ziad Fajloun, Rabih Roufayel, Ramy Haroun, Rita Khalil, Boutros Tannoury, Francis Kattoura, Majd El Hajj Moussa, Jean-Claude Lahoud, Charbel Tawk, Fadi Hoyek","doi":"10.3390/pathophysiology33030071","DOIUrl":"10.3390/pathophysiology33030071","url":null,"abstract":"<p><p><b>Introduction</b>: Inflammation is a central component of the biological processes involved in orthopedic interventions, whether performed for acute traumatic injuries or chronic non-traumatic conditions. Cytokines play major roles in modulating these responses; however, data describing cytokine activity in bone marrow, particularly during orthopedic procedures, remain limited. This study aimed to examine variations in cytokine levels in traumatic and non-traumatic orthopedic surgeries by analyzing simultaneous bone marrow and plasma samples. <b>Methods</b>: This single-center prospective observational study with exploratory objectives included skeletally mature patients undergoing urgent surgery for acute traumatic fractures or planned surgery for chronic non-traumatic degenerative orthopedic conditions. Bone-marrow and peripheral plasma samples were collected simultaneously intraoperatively. All samples were tested in duplicate for interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-1 receptor antagonist (IL-1RA), and tumor necrosis factor-α (TNF-α) using developmental ELISA kits. Cytokine levels were compared between traumatic and non-traumatic groups and between bone-marrow and plasma samples. <b>Results</b>: Nineteen participants were included, providing 19 bone-marrow samples and 15 plasma samples, with the number of available measurements varying among cytokines. Bone-marrow IL-10 was detected in three of five available traumatic samples and in none of the eight available non-traumatic samples (unadjusted <i>p</i> = 0.035; false-discovery-rate-adjusted <i>q</i> = 0.178). Plasma IL-1RA concentrations were higher in traumatic than in non-traumatic patients (median 2828.00 versus 1269.00 pg/mL; unadjusted <i>p</i> = 0.038; <i>q</i> = 0.178). Bone-marrow IL-8 also showed higher concentrations in traumatic patients and approached the unadjusted significance threshold (<i>p</i> = 0.053; <i>q</i> = 0.178). No comparison remained statistically significant after FDR correction. <b>Discussion</b>: Bone-marrow IL-10 detection and plasma IL-1RA concentrations showed nominal between-group differences that did not remain statistically significant after multiple-comparison adjustment. Although preliminary and hypothesis-generating, these observations identify potentially informative local and systemic cytokine patterns and highlight the value of further investigating bone-marrow cytokine responses in orthopedic trauma.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Oncology: Exploring the Expanding Role of CAR T Cell Therapy in Autoimmune and Infectious Diseases-A Systematic Review.","authors":"Kawther Zaher, Jehan Alrahimi","doi":"10.3390/pathophysiology33030070","DOIUrl":"10.3390/pathophysiology33030070","url":null,"abstract":"<p><p><b>Background:</b> Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of select hematologic malignancies and is increasingly being explored for non-oncological indications, including autoimmune diseases and persistent infectious diseases. This systematic review synthesized current evidence on CAR T cell and CAR-Treg approaches beyond oncology, with emphasis on therapeutic targets, translational and clinical outcomes, safety, and implementation barriers. <b>Methods:</b> The review followed PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and major trial registries were searched for studies published from 1 January 2010 to 31 March 2026. Eligible studies included clinical, preclinical, and translational investigations of CAR T cell or CAR-Treg strategies in autoimmune or infectious diseases. Results: Because of heterogeneity in disease indications, CAR constructs, endpoints, and study designs, findings were synthesized descriptively. The strongest early clinical signals were observed with B cell-directed CAR T cell therapy for severe, refractory autoimmune diseases, particularly systemic lupus erythematosus, systemic sclerosis, and inflammatory myopathies. Infectious disease applications, mainly HIV and hepatitis B, showed preliminary safety, persistence, and partial antiviral activity, but durable pathogen eradication remains unproven. Conclusion: Overall, CAR T cell therapy beyond oncology is promising but remains preliminary, requiring standardized reporting, long-term safety monitoring, scalable manufacturing, and carefully defined risk-benefit thresholds. Human clinical evidence was interpreted separately from preclinical and mechanistic evidence, and clinical conclusions were based primarily on human studies.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal Tone, Muscle Memory and Denervation: Pathophysiological Foundations of Abdominal Wall Hernia Development and Recovery.","authors":"Zelimkhan G M Berikkhanov, Zakhar A Akulov, Maria A Sukhanova, Alexey L Shestakov, Aleksey G Kotelnikov, Andrey M Nikolaev, Vadim S Razumovsky, Evgeniy A Tarabrin, Milena Yu Ivanova, Sergey Yu Muraviev","doi":"10.3390/pathophysiology33030069","DOIUrl":"10.3390/pathophysiology33030069","url":null,"abstract":"<p><p>Modern abdominal wall hernia surgery is centered on the biomechanics of the fascial-aponeurotic framework and on intra-abdominal pressure (IAP) control; neuromuscular regulation of the wall remains outside perioperative planning. This review reframes the abdominal wall as a coordinated neuromuscular system and outlines a framework in which ventral herniation is hypothesized to represent a compensatory response to altered regulation of elevated IAP, while discoordinated contraction of the muscular layers is proposed as a potential predisposing factor. A structured literature search was performed in PubMed/MEDLINE, Embase and the Cochrane Library from inception to March 2026 across four thematic blocks: basal tone and innervation, spinal pathology and coordination, skeletal muscle memory, and electromyographic and clinical models of denervation. Synthesis followed SANRA criteria. This is not a formal systematic review or meta-analysis. Basal tone of the abdominal muscles is individual and depends on spinal innervation, lifestyle, comorbidity, and hernia duration; obstructive pulmonary disease yields a hypertonic phenotype, and persistent meteorism a hypotonic one. In a patient predisposed to herniation, elevated IAP may be partially accommodated through redistribution of abdominal contents; within the proposed framework, herniation is hypothesized to function as a pressure-relief mechanism. Discoordination of the muscular layers may reduce the capacity of the abdominal wall to adapt to rapid or unfamiliar loading, potentially contributing to hernia formation in predisposed patients. Six meta-analyses of preoperative botulinum toxin type A confirm lateral muscle elongation; none assessed basal-tone recovery after toxin washout. Each hernia patient presents with an individual neuromuscular phenotype shaped by basal tone, intermuscular coordination and muscle memory. The proposed framework complements mechano-fascial concepts with a neurophysiological dimension and provides a hypothesis-generating rationale for investigating phenotype-tailored prehabilitation and postoperative rehabilitation. Prospective electromyographic mapping with functional maneuvers is the immediate research priority.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}